Cognitive functioning in children with self-limited epilepsy with centrotemporal spikes: A systematic review and meta-analysis

Summary

Objective

It is now well appreciated that benign epilepsy with centrotemporal spikes (BECTS, or more recently, ECTS) is associated with a range of cognitive and behavioral disturbances. Despite our improved understanding of cognitive functioning in ECTS, there have been to date no efforts to quantitatively synthesize the available literature within a comprehensive cognitive framework.

Methods

The present systematic review and meta-analysis was conducted according to PRISMA guidelines. Forty-two case–control samples met eligibility criteria comprising a total of 1,237 children with ECTS and 1,137 healthy control children. Univariate, random-effects meta-analyses were conducted on eight cognitive factors in accordance with the Cattell–Horn–Carroll model of intelligence.

Results

Overall, children with ECTS demonstrated significantly lower scores on neuropsychological tests across all cognitive factors compared to healthy controls. Observed effects ranged from 0.42 to 0.81 pooled standard deviation units, with the largest effect for long-term storage and retrieval and the smallest effect for visual processing.

Significance

The results of the present meta-analysis provide the first clear evidence that children with ECTS display a profile of pervasive cognitive difficulties and thus challenge current conceptions of ECTS as a benign disease or of limited specific or localized cognitive effect.

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Laparoscopic reversal of mini-gastric bypass to original anatomy for severe postoperative malnutrition

Abstract

Purpose

Malnutrition after mini-gastric bypass (MGB) is a rare and dreaded complication with few data available regarding its surgical management. We aim to report the feasibility, safety, and results of laparoscopic reversal of MGB to normal anatomy (RMGB) in case of severe and refractory malnutrition syndrome after intensive nutritional support (SRMS).

Methods

A 10-year retrospective chart review was performed on patients who underwent RMGB (video included) for SRMS following MGB.

Results

Twenty-six of 2934 patients underwent a RMGB at a mean delay of 20.9 ± 13.4 months post-MGB. At presentation, mean body mass index (BMI), excess weight loss (%EWL), and albumin serum level were 22 ± 4.4 kg/m², 103.6 ± 22.5%, and 25.5 ± 3.6 gr/L, respectively. Seventeen (63.5%) patients had at least one severe malnutrition related complication including severe edema in 13 (50%), venous ulcers in 2 (7.7%), infectious complications in 7 (27%), deep venous thrombosis in 5 (19.2%), and motor deficit in 5 (19.2%) patients. At surgical exploration, 8 of 12 (66.5%) patients had a biliary limb longer than 200 cm and 9 (34.6%) had bile reflux symptoms. Overall morbidity was 30.8% but lower when resecting the entire previous gastrojejunostomy with creation of a new jejunojejunostomy (8.3 vs 50%, p = 0.03). After a mean follow-up of 8 ± 9.7 months, all patients experienced a complete clinical and biological regression of the SRMS after the RMGB despite a mean 13.9 kg weight regain in 16 (61.5%) patients.

Conclusions

Post-MGB SRMS and its related comorbidities are rare but dreaded conditions. Although burdened by a significant postoperative morbidity and weight regain, RMGB remains an effective option to consider, when intensive nutritional support fails.

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Surgical approaches to adenocarcinoma of the gastroesophageal junction: the Siewert II conundrum

Abstract

Background

The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy.

Purpose

A review of the available evidence of the surgical management of Siewert II tumors is presented.

Conclusions

Careful review of the data appear to support the fact that a satisfactory oncologic resection can be achieved via a transabdominal extended total gastrectomy with a slight advantage in terms of perioperative complications, and overall postoperative quality of life. Overall and disease-free survival compares favorably to the transthoracic approach. These results can be achieved with careful selection of patients balancing more than just the Siewert type in the decision-making but considering also preoperative T and N stages, histological type (diffuse type requiring longer margins that are not always achievable via gastrectomy), and the presence of Barrett's esophagus.

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Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life

Abstract

As colorectal cancers have a long latency period, their origins may lie early in life. Therefore childhood body mass index (BMI; kg/m²) and height may be associated with adult colorectal cancer. Using a cohort design, 257,623 children from The Copenhagen School Health Records Register born from 1930 to 1972 with measured heights and weights at ages 7 to 13 years were followed for adult colon and rectal adenocarcinomas by linkage to the Danish Cancer Registry. Hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by Cox proportional hazard regressions. During follow-up, 2676 colon and 1681 rectal adenocarcinomas were diagnosed. No sex differences were observed in the associations between child BMI or height and adult colon or rectal cancers. Childhood BMI and height were positively associated with colon cancer; at age 13 years the HRs were 1.09 (95% CI 1.04–1.14) and 1.14 (95% CI 1.09–1.19) per z-score, respectively. Children who were persistently taller or heavier than average, had increased risk of colon cancer. Similarly, growing taller or gaining more weight than average was positively associated with colon cancer. No associations were observed between BMI or height and rectal cancer. Childhood BMI and height, along with above average change during childhood are significantly and positively associated with adult colon cancers, but not with rectal cancer, suggesting different etiologies.

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Activity Demands During Multi-Directional Team Sports: A Systematic Review

Abstract

Background

Late-stage rehabilitation programs often incorporate 'sport-specific' demands, but may not optimally simulate the in-game volume or intensity of such activities as sprinting, cutting, jumping, and lateral movement.

Objective

The aim of this review was to characterize, quantify, and compare straight-line running and multi-directional demands during sport competition.

Data Sources

A systematic review of PubMed, CINAHL, SPORTDiscus, and Cochrane Central Register of Controlled Trials databases was conducted.

Study Eligibility Criteria

Studies that reported time-motion analysis data on straight-line running, accelerations/decelerations, activity changes, jumping, cutting, or lateral movement over the course of an entire competition in a multi-directional sport (soccer, basketball, lacrosse, handball, field hockey, futsal, volleyball) were included.

Study Appraisal and Synthesis Methods

Data was organized based on sport, age level, and sex and descriptive statistics of the frequency, intensity, time, and volume of the characteristics of running and multi-directional demands were extracted from each study.

Results

Eighty-one studies were included in the review (n = 47 soccer, n = 11 basketball, n = 9 handball, n = 7 field hockey, n = 3 futsal, n = 4 volleyball). Variability of sport demand data was found across sports, sexes, and age levels. Specifically, soccer and field hockey demanded the most volume of running, while basketball required the highest ratio of high-intensity running to sprinting. Athletes change activity between 500 and 3000 times over the course of a competition, or once every 2–4 s. Studies of soccer reported the most frequent cutting (up to 800 per game), while studies of basketball reported the highest frequency of lateral movement (up to 450 per game). Basketball (42–56 per game), handball (up to 90 per game), and volleyball (up to 35 per game) were found to require the most jumping.

Limitations

These data may provide an incomplete view of an athlete's straight-line running load, considering that only competition and not practice data was provided.

Conclusions

Considerable variability exists in the demands of straight-line running and multi-directional demands across sports, competition levels, and sexes, indicating the need for sports medicine clinicians to design future rehabilitation programs with improved specificity (including the type of activity and dosage) to these demands.

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Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients

Abstract

Purpose

Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients.

Methods

This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000–2009 from National Health Insurance Program database.

Results

A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61–0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72–0.91) and matched populations (0.86; 0.78–0.95).

Conclusion

This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

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Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life

Abstract

As colorectal cancers have a long latency period, their origins may lie early in life. Therefore childhood body mass index (BMI; kg/m²) and height may be associated with adult colorectal cancer. Using a cohort design, 257,623 children from The Copenhagen School Health Records Register born from 1930 to 1972 with measured heights and weights at ages 7 to 13 years were followed for adult colon and rectal adenocarcinomas by linkage to the Danish Cancer Registry. Hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by Cox proportional hazard regressions. During follow-up, 2676 colon and 1681 rectal adenocarcinomas were diagnosed. No sex differences were observed in the associations between child BMI or height and adult colon or rectal cancers. Childhood BMI and height were positively associated with colon cancer; at age 13 years the HRs were 1.09 (95% CI 1.04–1.14) and 1.14 (95% CI 1.09–1.19) per z-score, respectively. Children who were persistently taller or heavier than average, had increased risk of colon cancer. Similarly, growing taller or gaining more weight than average was positively associated with colon cancer. No associations were observed between BMI or height and rectal cancer. Childhood BMI and height, along with above average change during childhood are significantly and positively associated with adult colon cancers, but not with rectal cancer, suggesting different etiologies.

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Accelerated Long-Term Forgetting Is Not Epilepsy Specific: Evidence from Childhood Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Mediating burden and stress over time: Caregivers of patients with primary brain tumor

Abstract

There is a growing literature on the effects of cancer caregiving on the well-being of informal family caregivers. However, there has been little longitudinal research on caregivers of patients with the complex, rapidly-changing disease of primary malignant brain tumor (PBT).

Objective

Our objective was to model longitudinal relationships between caregiver burden, social support, and distress within caregivers of patients with PBT.

Methods

Caregiver participants were recruited from a neuro-oncology clinic. Caregiver questionnaire data, including socio-demographics, social support, depression, anxiety, and caregiving burden, were collected at four time points (diagnosis, +4, +8, and +12 months). Using the stress process model as a guide, we hypothesized that early burden would predict later depression and anxiety and this would be mediated by social support.

Results

Using data from 147 participants, we found support for the stress process model in caregivers of patients with PBT. Greater burden at diagnosis was associated with lower social support at 4 months and lower social support was related to higher depression and anxiety at 8 months, as well as to changes in anxiety between 8 and 12 months.

Conclusion

We found evidence of the stress process model in caregivers of PBT patients unfolding over the course of a year after diagnosis. Our findings emphasize the potential importance of early programs for caregivers to ensure low initial levels of burden, which may have a positive effect on social support, depression, and anxiety.

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Mineralization-defects are comparable in fluorotic impacted human teeth and fluorotic mouse incisors

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Rozita Jalali, Franck Guy, Samaneh Ghazanfari, Don Lyaruu, Leo van Ruijven, Pamela DenBesten, Stefania Martignon, Gina Castiblanco, Antonius L.J.J. Bronckers
ObjectiveFluoride excess of 0.05–0.07mgF/kgbw/day in water or food additives like salt is the principal cause of endemic dental fluorosis. How fluoride causes these defects is not clear yet. Recent studies in rodents suggest that development of enamel fluorosis is associated with insufficient neutralization of protons released during the formation of hypermineralized lines.DesignHere we examined whether hypermineralization could also be assessed by MicroCT in developing molar enamel of humans exposed to fluoride.ResultMicro-CT analysis of hypomineralized enamel from human fluorotic molars graded by the Thylstrup–Fejerskov (TF) Index as III–IV showed weak hypermineralized lines and hypermineralized patches not seen in TF-I/II grade enamel. The mesio-distal sides of these molar teeth were significantly smaller (∼18%, p=0.02) than in TF-I/II teeth.ConclusionThe patterns of changes observed in human fluorotic teeth were similar to those in fluorotic rodent incisors. The data are consistent with the hypothesis that also in developing human teeth fluoride-stimulated local acidification of enamel could be a mechanism for developing fluorotic enamel.



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Cervical mass as the first clinical manifestation of unsuspected metastatic seminoma

The authors reported a case of a 27‐year‐old man with a nontender left neck mass that had grown quite rapidly within few weeks. FNAB and CT were not consistent to establish the definite diagnosis. After excisional biopsy, the histopathological examination and the immunohistochemical study of the specimen revealed a cervical metastasis of seminoma. The patient was treated with chemotherapy with a complete clinical remission. This uncommon case-report can represent a great diagnostic and therapeutic challenge and should be considered in the differential diagnosis of every cervical masses occurring in young males patients.

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Does CT help in predicting preepiglottic space invasion in laryngeal carcinoma?

Evaluating preepiglottic space involvement in laryngeal cancer by CT may lead misinterpretation. We sought to understand the causes of misinterpretation in evaluating the preepiglottic space by CT and assessed the effects of misinterpretation in treatment plans of patients with laryngeal squamous cell carcinomas.

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Correlation of soft palate length with velum obstruction and severity of obstructive sleep apnea syndrome

Our aim in this study was to analyze whether soft palate length and velum obstruction during sleep are correlated and to determine the effects of related parameters on obstructive sleep apnea syndrome (OSAS) severity. We used computed tomography to measure soft palate length and drug-induced sleep endoscopy (DISE) to evaluate velum obstruction severity. Patients also underwent polysomnography (PSG) for evaluation of OSAS severity.

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Clinical course of incidental parathyroidectomy: Single center experience

Thyroidectomy is a very common surgical procedure. Regardless of surgeon experience, incidental parathyroidectomy is a complication of thyroidectomy. The aim of this study was to identify the clinical course of incidental parathyroidectomies after thyroidectomy.

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Disruption of frontal-parietal connectivity during conscious sedation by propofol administration.

The sedative state is a transitional state from wakefulness to general anesthesia. However, little is understood regarding the mechanism of conscious sedation, different from general anesthesia while maintaining wakefulness. In this study, we aimed to investigate changes in functional connectivity of the parietal-frontal network, implicated in wakefulness during conscious sedation induced by propofol infusion. The electroencephalography was obtained at the frontal and parietal areas of adult volunteers who maintain wakefulness during low-dose propofol infusion (1.5 mg/kg/h) over 1 h. Spectral Granger causality (GC) ([delta], [theta], [alpha], [beta], and [gamma] frequency bands) and time-domain GC were calculated during each stage of awake (before propofol administration), sedation, and recovery (after discontinuation of propofol). We also calculated the phase-locking index and compared it with GC during each stage. A decrease in GC from the frontal to parietal areas was observed particularly in the low-frequency bands during propofol administration. Contrary to the GC changes in the frontoparietal direction, GC from the parietal to frontal areas was increased in the high-frequency bands during propofol administration and significantly decreased after discontinuation of propofol. In summary, we showed that frontal-parietal neural networks were significantly changed differently by the frequency of the brain rhythm and the directions of connections during sedation by propofol administration. Our result suggests that the alteration of brain interaction may induce sedative state lying between awake and general anesthesia. (C) 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Accelerated Long-Term Forgetting Is Not Epilepsy Specific: Evidence from Childhood Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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In Response.

No abstract available

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In Response: Concerns With Rate of Rise of Carbon Dioxide During Apnea With Buccal Oxygenation.

No abstract available

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The Subtleties of Language as a Reason for Failure to Follow Preoperative Fasting Guidelines: The Differences Between Restricting, Allowing, and Encouraging.

No abstract available

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Core Temperature Monitoring in Obstetric Spinal Anesthesia Using an Ingestible Telemetric Sensor.

BACKGROUND: Perioperative hypothermia may affect maternal and neonatal outcomes after obstetric spinal anesthesia. Core temperature is often poorly monitored during spinal anesthesia, due to the lack of an accurate noninvasive core temperature monitor. The aim of this study was to describe core temperature changes and temperature recovery during spinal anesthesia for elective cesarean delivery. We expected that obstetric spinal anesthesia would be associated with a clinically relevant thermoregulatory insult (core temperature decrease >1.0[degrees]C). METHODS: A descriptive study was conducted in 28 women. An ingestible telemetric temperature sensor was used to record core temperature over time (measured every 10 seconds). The primary outcome was the maximum core temperature decrease after spinal anesthetic injection. The secondary outcomes were lowest absolute core temperature, time to lowest temperature, time to recovery of core temperature, hypothermic exposure (degree-hours below 37.0[degrees]C), and the time-weighted hypothermic exposure (median number of degrees below 37.0[degrees]C per hour). Basic descriptive statistics, median spline smooth, and integration of the area below the 37.0[degrees]C line of the temperature-over-time curve were utilized to analyze the data. RESULTS: Intestinal temperature decreased by a mean (standard deviation) of 1.30[degrees]C (0.31); 99% confidence interval (CI), 1.14 to 1.46 after spinal anesthetic injection. The median (interquartile range [IQR]) time to temperature nadir was 0.96 (0.73-1.32) hours (95% CI, 0.88-1.22). Fourteen of the 28 participants experienced intestinal temperatures below 36.0[degrees]C after spinal injection. Temperature was monitored for a minimum of 8 hours after spinal injection. In 8 of 28 participants, intestinal temperature did not recover to baseline during the monitored period. A median (IQR) of 4.59 (3.38-5.92) hours (95% CI, 3.45-5.90) was required for recovery to baseline intestinal temperature in the remaining 20 patients. Participants experienced a median (IQR) of 1.97 (1.00-2.68) degree-hours of hypothermic exposure (95% CI, 1.23-2.45). The median (IQR) number of degrees below 37.0[degrees]C per hour was 0.45 (0.35-0.60) (95% CI, 0.36-0.58). CONCLUSIONS: During cesarean delivery under spinal anesthesia, women experienced a rapid decrease in core temperature. Using an intestinal telemetric sensor, the perioperative thermal insult and recovery were documented with high resolution. Fifty percent of participants in this study became hypothermic. Although the surgical procedure is typically of short duration, women undergoing spinal anesthesia for cesarean delivery experience significant hypothermic exposure and compromised thermoregulation for several hours. (C) 2017 International Anesthesia Research Society

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Reducing Mortality in Acute Kidney Injury.

No abstract available

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Necrotic mucosal CD30-positive ulcer on the oral mucosa: a self-healing lymphoma

We report the case of a peripheral mucosal lymphoma that developed in the oral cavity and had a self-limiting course.

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Postoperative complications after head and neck operations that require free tissue transfer- prevalence, morbidity, and cost

To understand and reduce the impact of postoperative complications, we studied 568 patients who had had operations over 72 months in our hospital. Multivariate analysis indicated that factors indicative of coexisting conditions (including activated systemic inflammation) and the complexity of the operation are primary determinants of postoperative complications. The enhanced recovery after surgery (ERAS) care pathway did not have an effect on their occurrence or severity. Systematic study of patients' toleration of major head and neck operations is required, as optimal perioperative care pathways remain elusive.

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Hearing Health USA and Belsono Partner to Remove Stigma of Hearing Aids

​Two national hearing heath center networks, Hearing Health USA and Belsono Hearing Centers, are partnering for the #FlauntYourHearingAids campaign to encourage an open dialogue about hearing loss and hearing aid use by showing that anyone can be affected but not limited by hearing loss. The campaign will feature a combination of visual materials and informational articles highlighting people doing amazing things while wearing their hearing aids. From now until the end of September, hearing aid users are invited to submit photos of themselves or their loved ones flaunting their hearing aids for a chance to be featured on the two companies' website and social media pages. Those interested in participating can submit their photos on Twitter, Facebook, and Instagram with the hashtag #FlauntYourHearingAids, or upload them to the websites of Hearing Health USA and Belsono (http://bit.ly/2vW4nok; http://bit.ly/2vVElRW). 

Published: 8/11/2017 12:10:00 PM

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Validation study of accelerometer in measuring some sleep parameters in adults

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Validation study of accelerometer in measuring some sleep parameters in adults

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A Limited Submuscular Direct-to-Implant Technique Utilizing AlloMax

Background: This study evaluates a novel limited submuscular direct-to-implant technique utilizing AlloMax where only the upper few centimeters of the implant is covered by the pectoralis, whereas the majority of the implant including the middle and lower poles are covered by acellular dermal matrix. Methods: The pectoralis muscle is released off its inferior and inferior-medial origins and allowed to retract superiorly. Two sheets of AlloMax (6 × 16 cm) are sutured together and secured to the inframammary fold, serratus fascia, and the superiorly retracted pectoralis. Thirty-seven breasts in 19 consecutive patients with follow-up at 6 months were reviewed. Results: Nineteen consecutive patients with 37 reconstructed breasts were studied. Average age was 50 years, average BMI was 24.3. Ptosis ranged from grade 0–III, and average cup size was B (range, A–DDD). Early minor complications included 1 seroma, 3 minor postoperative hematomas managed conservatively, and 3 minor wound healing problems. Three breasts experienced mastectomy skin flap necrosis and were managed with local excision. There were no cases of postoperative infection, red breast, grade III/IV capsular contractures, or implant loss. A single patient complained of animation postoperatively. One patient desired fat grafting for rippling. Conclusions: The limited submuscular direct-to-implant technique utilizing AlloMax appears to be safe with a low complication rate at 6 months. This technique minimizes the action of the pectoralis on the implant, reducing animation deformities but still providing muscle coverage of the upper limit of the implant. Visible rippling is reduced, and a vascularized bed remains for fat grafting of the upper pole if required.

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The Supra-Inframammary Fold Approach to Breast Augmentation: Avoiding a Double Bubble

Background: The inframammary incision for breast augmentation is commonly made at or below the existing inframammary fold (IMF) in an effort to keep the scar in the crease. In recent studies, surgeons inferiorly relocate the IMF, center the implant at nipple level, and attempt to secure the new IMF with sutures. The fascial attachments (also called ligaments) holding the IMF are released, risking a bottoming-out deformity or a double bubble. Methods: This retrospective study evaluated 160 consecutive women undergoing primary subpectoral breast augmentation. An incision was made 0.5–1.0 cm above the IMF. Dissection proceeded directly to the pectoralis margin, preserving IMF fascial attachments. The pectoralis origin was released from the lower sternum. Surveys were administered to obtain patient-reported outcome data. Ninety-eight patients (61%) participated. Results: Implants often appear high on the chest at early follow-up appointments but gradually settle. One patient (0.6%) developed a double bubble. No reoperations were needed for implant malposition. One patient had a mild animation deformity. There were no cases of symmastia. The mean result rating was 9.1/10. Four percent of surveyed patients found their implants too high; 8% found them too low. Ninety-two patients (94%) reported that their scars were well-hidden. Ninety-six women (98%) said that they would redo the surgery. Conclusions: A supra-IMF approach anticipates the normal descent of implants after augmentation. Scars remain hidden both in standing and supine positions. This method reduces the short-term risk of reoperation for implant malposition or a double bubble.

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Palliative external beam radiotherapy for the treatment of tumor bleeding in inoperable advanced gastric cancer

Abstract

Background

To assess the outcomes and prognostic factors associated with palliative external beam radiotherapy (EBRT), administered to patients with advanced gastric cancer.

Methods

Forty-two patients with bleeding gastric tumors that received EBRT for palliation were analyzed. The response to EBRT was assessed by the palliation of tumor bleeding. Patients were classified as either responders, or non-responders to EBRT. The prognostic utility of clinical and dosimetric variables was examined in a multivariate logistic regression model. The optimal dose cutoff to classify the two groups was determined with receiver operating characteristic analysis.

Results

The palliation of gastric tumor bleeding after EBRT was achieved in 29 patients (69.0%). The time to resolve tumor bleeding ranged from 1 to 84 days (median, 15 days). The median duration of palliation was 14.9 weeks. The median EBRT dose was 40 Gy in responders vs. 21 Gy in non-responders, with the difference being significant (p < 0.001). The biologically effective dose (using α/β = 10, BED₁₀) for responders was significantly higher than the BED₁₀ for non-responders (median 48 Gy vs. 26.4 Gy, p < 0.001), and the optimal cut off value to separate the two groups was 36 Gy (p < 0.001). The absence of distant metastasis and the use of concurrent chemotherapy generally showed a better EBRT response (p = 0.079 and p = 0.079, respectively). In the multivariate analysis, BED₁₀ ≥ 36 Gy was the most significant factor associated with EBRT response (p = 0.001). Overall survival (OS) and re-bleeding-free survival was median 12.6 weeks and 14.9 weeks. The responders to EBRT showed superior OS (16.6 vs. 5.1 months, p < 0.001). Neither acute nor chronic toxicities of grade 3 or higher were observed.

Conclusions

EBRT is an effective method for treating tumor bleeding in advanced gastric cancer, and does not induce severe toxicity.

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Beliefs and perceptions that impair cleft care treatment in Madagascar: A qualitative study during humanitarian mission

Nirina Adrien Jean Vivier Mandrano, Yasuyoshi Tosa, Tomoaki Kuroki, Nobuhiro Sato, Shinya Yoshimoto

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):149-153

Context: During humanitarian cleft care mission in developing countries, a considerable noncompliance of the patient remains evident despite the provided medical support. According to the literature, social background and beliefs are some of the factors that hamper cleft management in these areas. Aims: In this study, we investigated on these impairments for a better approach to cleft care in Madagascar. Settings and Design: This is a qualitative study conducted in Clinic Ave Maria, Antsirabe, Madagascar, which interviewed parents and patients. Subjects and Methods: One adult patient and nineteen parents of a patient with cleft lip and palate (CLP) were interviewed for a qualitative study. An open-ended, closed-ended semistructured interview was conducted. Results: Analysis of the interview result and a literature discussion were performed. The most believed cause of cleft lip was supernatural forces, diet, and a curse, leading to a strong self-blame and shame inside the community. Thus, CLP is thought to be a supernatural disease, which cannot be totally healed by injection and surgery. A belief leads to a delay, denial of medical care, and/or ignorance and rejection of new explanations. Conclusions: Social background and beliefs of our Malagasy community have a considerable impact on how the patients perceive cleft deformity. These perceptions strongly influence the patient's compliance to medical care. Considering education as a part of the treatment plan during a humanitarian mission can modify the patient's attitude and improve their motivation to a better treatment outcome.

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Pathologic anatomy of the soft palate, part 2: The soft tissue lever arm, pathology, and surgical correction

Michael H Carstens

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):83-108

Pathologic anatomy of the soft palate, part 2: The soft tissue lever arm, pathology, and reconstruction. In part two, we consider the soft tissue components of the soft palate: Epithelium, fascia, muscles, arterial supply, and innervation. These velar tissues constitute a functional "lever arm" for control of speech and swallowing. Fascia and peripheral nerves arise neural crest originating from rhombomeres 2–7. Muscles arise from paraxial mesoderm (PAM) of somitomeres 4, 6, and 7. Lateral plate mesoderm lying outside of PAM provides the building blocks of the circulatory system. Neurovascular analysis discloses the soft palate to have three developmental zones with distinct sources of neurovascular supply. Emphasis is placed on the anterior third of the palatine aponeurosis; this critical structure determines where the levator complex will insert. The basic field defect of soft palate clefts arises from insufficiency of the lesser palatine neurovascular pedicle affecting the posterior palatine shelf and anterior 1/3 of the palatine aponeurosis. This leads to forward displacement of the levator complex and pathologic insertion onto the bony margin of the cleft site. Soft-tissue disruption will then be presented in terms of the simple genetic loop between bone morphogenetic protein 4 (BMP-4) and Sonic hedgehog. The migration of soluble factors such as BMP-4 from their origin with developing bone to the free border of the epithelium permitting fusion of adjacent structures.

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Tongue harmatoma in association with cleft palate: Case report

Uwakwe Cosmas Mba, Ifeanyi Igwilo Onah

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):168-169

Tongue hamartoma is not a common congenital disorder. Common associations include cardiac defects and limb anomalies such as polydactyly and syndactyly. Its association with cleft palate is unusual and as such only very few cases have been reported. A 15-month-old girl who presented to us with a mass on the tongue in association with cleft of the soft palate is presented. She had cleft palate repair and incisional biopsy of the mass. Initial histology was lipoma. The mass was excised a year later and histology confirmed lipomatous harmatoma.

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Impact of educational and socioeconomic status of parents on healthcare access in cleft patients

Divya Narain Upadhyaya, Guru Prasad Reddy, Raj Kumar Mishra, Arun Kumar Singh

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):109-113

Introduction: There is a wide disparity in the access to treatment facilities between developed and developing countries in cleft lip and palate (CLP) management. Factors ranging from poverty and illiteracy to paucity of healthcare services affect the patient accessing these services. Objective: Information regarding the socioeconomic and educational status of the parents of CLP patients admitted in a tertiary centre in Northern India was collected and analyzed to find any correlation between the above and the age of child at the first presentation to the hospital. Methods: Data were collected from parents of 200 consecutive patients of CLP presenting for surgery. The data set included variables such as age and sex of the child, age and literary status of the parents, household income, distance to the hospital from home, and the source of information that made them visit the hospital. Results and Conclusion: There was significant association between the age of first presentation and the literary status of the mother and father (P = −0.005 and 0.02, respectively), socioeconomic status of the family (P = −0.02), and the distance from the hospital. Other observations, though impressive, were not statistically significant. This proves the impact of socioeconomic and literary status of parents on availing access to healthcare services for their children.

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Morbidity associated with anterior iliac crest harvesting for osseous reconstruction of alveolar clefts

Abhilasha Yadav, Anuj Jain, Rohan Deshpande, Rajiv Borle, Suhas Jajoo, Apeksha Yadav

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):158-163

Introduction: The anterior iliac crest is considered the best site for harvesting autogenous bone graft for reconstruction of alveolar cleft since decades. As it is with the other sites of autogenous bone graft harvesting, anterior iliac crest also results in postoperative morbidity. The purpose of this study is to assess the associated postoperative morbidity with anterior iliac crest harvesting in the treatment of individual with alveolar clefts. Patients and Methods: A total of 92 patients with alveolar clefts were treated with autogenous bone grafting harvested from the anterior iliac crest in the duration from January 2009 to December 2014. Postoperatively, on day 1, day 7, 1st month, 3rd month, and 6th month, morbidity was assessed in these patients with postoperative pain, gait disturbance, sensory disturbance, and scarring being the parameters of assessment. Results: Postoperative pain was a complaint of all the patients on day 1 which reduced to 3.26% of patients on day 7 and after 1 month revealed no patients was experiencing pain. On day 1, 69.57% of patients and 97.83% of patients complained of sensory and gait disturbances, respectively. These numbers decreased to 6.52% and 8.7%, respectively, on day 7th, further decreasing to 2.17% and 1.09%, respectively, after 1 month. None of the patients had gait and sensory disturbances after 3 months. On scar evaluation, only one patient had a hypertrophic scar at the end of 6 months postoperatively. None of the parameters were statistically significant on completion of the 1st, 3rd, and 6th month. Conclusion: Anterior iliac crest can still be continued to be considered a first option for harvesting autogenous bone graft for rehabilitation of patients with alveolar clefts as it is well tolerated by them. It has low morbidity which allows early resumption of normal activities and has a reasonable esthetic outcome.

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Effect of palatoplasty on hearing ability of nonsyndromic cleft palate patients: A prospective clinical study

Anuj Jain, Abhilasha Yadav, Nitin Bhola, Pranali Nimonkar, Rajiv Borle

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):114-119

Introduction: Cleft palate patients suffer from many comorbidities, otitis media with effusion being one of them. There is a universal consensus regarding the presence of hearing impairment in such patients. However, there are different schools of thought regarding the effect of palatal repair on hearing ability. Hence, this study was conducted to find out the effect of palatoplasty on hearing ability of children with cleft palate. Patients and Methods: Seventy-five patients with cleft palate underwent palatoplasty and were subjected to otoscopy and brainstem evoked response audiometry, preoperatively, 1 month postoperatively and 6 months postoperatively. The otoscopy and audiometry findings were statistically analyzed using Chi-square test and students unpaired t-test. Results: Ninety-two percent of patients had hearing impairment with majority of them belonging to age group <3 years. The study showed a male preponderance. Statistical analysis revealed that there was no significant difference between the preoperative and 1 month postoperative outcomes of otoscopy and audiometry. However, the values show a statistically significant improvement 6 months postoperatively. Conclusion: There is a marked association between hearing impairment and cleft palate. Moreover, this impaired hearing improves after palatoplasty in due course of time.

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Newer training tool in cleft lip and palate surgery

Karoon Agrawal

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):81-82



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Velopharyngeal dysfunction of neurogenic origin: Evaluating the use of gel implant injection augmentation

Khurram Khan, Michael Cadier

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):120-124

Objectives: Velopharyngeal dysfunction (VPD) secondary to neuromuscular pathology is well recognized. Surgical treatment in these patients using palatoplasty or conventional sphincteric and posterior flap-based pharyngoplasty is often contraindicated as they may further weaken or aggravate already impaired musculature. We report a small case series of patients who underwent successful long-term treatment for VPD of neurogenic origin using an injectable gel polymer to augment the posterior pharyngeal wall. Design: Three patients in whom a neuromuscular condition had led to the development of VPD underwent augmentation pharyngoplasty. Speech was compared pre- and post-operatively examining hypernasality, nasal emission, and nasalance scores and patient self-evaluation of outcome. Results: All three patients had improvement in parameters measured following pharyngeal injection augmentation. One patient noticed deterioration in speech intelligibility following initial injection into the velum: the implant polymer was easily removed and later reinjected in the posterior pharynx with good effect. Conclusions: The use of gel polymer injection pharyngoplasty in the treatment of neurogenic VPD was safe, simple, well tolerated, and easily reversible. However, due to recent severe complications reported from fat augmentation pharyngoplasty, we would not recommend its routine usage.

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Autologous alveolar bone graft integration based on the Bergland scale in patients with primary lip and palate cleft: Experience in a third level hospital in Mexico City

Araceli Perez-Gonzalez, Kenji Shinji-Pérez, Alberto Theurel-Cuevas, Yusef Jimenez-Murat, Jorge Raúl Carrillo-Córdova

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):154-157

Introduction: Alveolar bone graft surgery is of crucial importance in the cleft lip and palate patient. Adequate integration of the bone promotes dentition and esthetic of the face. The aim of this study is to evaluate the integration of the bone graft in patients with primary palate cleft. Patients and Methods: We made a retrospective analysis of medical records and plain X-ray films of 37 patients undergoing bone graft surgery in a tertiary care center. To assess the integration rate, we used the Bergland scale. Integration of alveolar bone graft evaluated with orthopantomography and relation between sex and the type of alveolar cleft surgery in the bone integration. Results: About 65% of the patients in our series were male (24). There was no statistical difference between the age, sex, and diagnosis. Mean age of the patients was 10.2 years. Successful integration (Bergland scale I and II) was achieved in 49% of the patients (Grade I: 30% and Grade II: 19%). Unfavorable integration (Bergland scale III and IV) was demonstrated in 51% of the patients, (Grade III: 43% and Grade IV: 8%). We found no difference between the integration rate and the type of alveolar graft surgery (primary, conventional secondary, and late secondary). Conclusions: Using the Bergland scale, we demonstrated 49% successful integration of the alveolar bone analyzed by two experts. Age has no impact on the integration rates in these groups of patients.

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Studying the impact of cleft of lip and palate among adults using the international classification of functioning, disability and health framework

Sri Ram M Reddy, B Subramaniyan, Roopa Nagarajan

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):125-137

Objectives: The study was conducted to document the impact of the cleft of lip and palate among adults using International Classification of Functioning, Disability and Health (ICF) framework. Design: This was a cross-sectional study. Participants: A total of 32 adults with cleft lip and palate (CLP) and a matched control group of 32 adults without CLP (non-CLP [NCLP]) were included in the study. Methods: To identify a set of items from ICF framework that is relevant to adults with CLP (ICF-CLP item set) from the components of activity participation and environmental factors. Two expert teams were involved in the selection of the final set of items from both the components. Then, the item set (ICF-CLP item set) was developed in Tamil. ICF-CLP item set in Tamil was piloted on 32 adults with repaired CLP and a matched control group of adults without CLP (NCLP) group by self-administering method. Results: There was a significant difference (P = 0.000) between CLP and NCLP group, in both the components –activity participation and environmental factors. In the item-wise comparison, individuals with CLP had a greater limitation in activity, restriction in participation in the domains of communication, maintaining interpersonal interactions and relationships, employment, and major life areas. In environmental factors, the domains of support, relationship, health services, education training systems and policies, attitudes of authorities, and strangers were projected as barriers by individuals with CLP. Conclusion: This study helps us in understanding the overall impact of the cleft of lip and palate among adults in the components of activity participation and environmental factors using the ICF framework. On the other hand, the ICF-CLP item set developed is clinically relevant in identifying conditions which limit activities/participation and serve as barriers/facilitators in their environments both in CLP population as well as in normal individuals.

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Prosthodontic rehabilitation of velopharyngeal insufficiency with definitive obturator

Puja Hazari, Sunil Kumar Mishra, Amit Khare

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):164-167

Velopharyngeal insufficiency resulted from the defect in soft palate due to acquired or congenital reasons, which cause incomplete closure of the palatopharyngeal sphincter. The individual with such defect faces problem in eating, speaking, breathing as well as faces psychological trauma in society. This article presents a case report of a patient with congenital velopharyngeal defect. A definitive cast partial prosthesis with a hollow acrylic bulb obturator was planned for the patient. This case report presents a modified impression technique for making definitive obturator along with cast partial denture for better retention and stabilization of the prosthesis. The prosthesis increases the acceptance as it prevents the hypernasality; improve mastication and speech of the patient.

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Effectiveness of a training program for community-based resource workers on cleft lip and palate and cleft speech

Subha Shunmugam, B Subramaniyan, Roopa Nagarajan, Savitha Vadakkanthara Hariharan

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):138-148

Objective: This study evaluated the training module which was developed for resource workers in the community, to impart knowledge about cleft lip and/or palate (CLP) and skill to identify error patterns in speech of individuals with CLP. Design: This was a cross-sectional study. Method: This study is a part of an ongoing community based rehabilitation project conducted in a rural district of South India. A total of 47 resource workers belonging to a rural district served as participants of this study. Pre and post training measures were compared to examine the effectiveness of the training program. Knowledge about CLP and ability to identify error patterns in speech of individuals with CLP by the resource workers were measured pre and post training to examine the effectiveness of the training program. Results: There was a statistically significant improvement in the resource workers' knowledge about CLP. Resource workers were able to identify the abnormal productions but were inconsistent in categorizing the specific error patterns. Conclusions: The post training results revealed improvement in the resource worker's understanding of CLP and ability to identify speech patterns in individuals with CLP. It can be inferred that with periodic retraining, resource workers can be trained to identify speech error patterns in individuals with CLP. Trained resource workers could probably be used to provide speech services under the supervision of speech-language pathologist (SLP) in places where SLPs are not available locally to provide direct therapy.

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Developing a new scissor for cleft surgery: The cleft palate dissection scissor

Till Wagner

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(2):170-171



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Technique of Laparoscopic Hysterectomy and Pelvic Lymphadenectomy for Endometrial Cancer

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Breast Cancer Immunotherapy: Facts and Hopes

Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of PD-1/PD-L1 antagonists in small numbers of metastatic breast cancer patients. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of TILs. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple negative breast cancer (TNBC), suggesting these agents may transform the lives of responding patients. Current clinical efforts are focused on developing immunotherapy combinations that convert non-responders to responders, deepen those responses that do occur, and surmount acquired resistance to immunotherapy. Identifying biomarkers that can predict the potential for response to single agent immunotherapy, identify the best immunotherapy combinations for a particular patient, and guide salvage immunotherapy in patients with progressive disease are high priorities for clinical development. Smart clinical trials testing rational immunotherapy combinations that include robust biomarker evaluations will accelerate clinical progress, moving us closer to effective immunotherapy for almost all breast cancer patients.

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Simultaneous targeting of two distinct epitopes on MET effectively inhibits MET- and HGF-driven tumor growth by multiple mechanisms

Increased MET activity is linked with poor prognosis and outcome in several human cancers currently lacking targeted therapies. Here we report on the characterization of Sym015, an antibody mixture composed of two humanized IgG1 antibodies against non-overlapping epitopes of MET. Sym015 was selected by high-throughput screening searching for antibody mixtures with superior growth inhibitory activity against MET-dependent cell lines. Synergistic inhibitory activity of the antibodies comprising Sym015 was observed in several cancer cell lines harboring amplified MET locus and was confirmed in vivo. Sym015 was found to exert its activity via multiple mechanisms. It disrupted interaction of MET with the HGF ligand and prompted activity-independent internalization and degradation of the receptor. In addition, Sym015 induced high levels of CDC and ADCC in vitro. The importance of these effector functions was confirmed in vivo using an Fc-effector-function attenuated version of Sym015. The enhanced effect of the two antibodies in Sym015 on both MET degradation and CDC and ADCC is predicted to render Sym015 superior to single antibodies targeting MET. Our results demonstrate strong potential for use of Sym015 as a therapeutic antibody mixture for treatment of MET-driven tumors. Sym015 is currently being tested in a phase I dose escalation clinical trial (NCT02648724)

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The combination of metformin and valproic acid induces synergistic apoptosis in the presence of p53 and androgen signaling in prostate cancer

We investigated the potential of combining the hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA), which act via different biochemical pathways, to provide enhanced anti-tumor responses in prostate cancer. Prostate cancer cell lines (LNCaP and PC-3), normal prostate epithelial cells (PrEC), and patient-derived prostate tumor explants were treated with MET and/or VPA. Proliferation and apoptosis were assessed. The role of p53 in response to MET+VPA was assessed in cell lines using RNA interference in LNCaP (p53⁺) and ectopic expression of p53 in PC-3 (p53^-). The role of the androgen receptor (AR) was investigated using the AR antagonist, Enzalutamide. The combination of MET and VPA synergistically inhibited proliferation in LNCaP and PC-3, with no significant effect in PrEC. LNCaP, but not PC-3, demonstrated synergistic intrinsic apoptosis in response to MET+VPA. Knock-down of p53 in LNCaP (p53⁺, AR⁺) reduced the synergistic apoptotic response as did inhibition of AR. Ectopic expression of p53 in PC-3 (p53^-, AR^-) increased apoptosis in response to MET+VPA. In patient-derived prostate tumor explants, MET+VPA also induced a significant decrease in proliferation and an increase in apoptosis in tumor cells. In conclusion, we demonstrate that MET+VPA can synergistically kill more prostate cancer cells than either drug alone. The response is dependent on the presence of p53 and AR signaling which have critical roles in prostate carcinogenesis. Further in vivo/ex vivo pre-clinical studies are required to determine the relative efficacy of MET+VPA as a potential treatment for prostate cancer.

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TDP1 is critical for the repair of DNA breaks induced by sapacitabine, a nucleoside also targeting ATM- and BRCA-deficient tumors

2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes beta-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes non-phosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage. We show that cells lacking TDP1 (avian TDP1-/- DT40 cells and human TDP1 KO TSCER2 and HCT116 cells) exhibit marked hypersensitivity to CNDAC. We also identified BRCA1, FANCD2 and PCNA in the DNA repair pathways to CNDAC. Comparing CNDAC with the chemically related arabinosyl nucleoside analog, cytosine arabinoside (cytarabine, AraC) and the topoisomerase I inhibitor camptothecin (CPT), which both generate 3'-end blocking DNA lesions that are also repaired by TDP1, we found that inactivation of BRCA2 renders cells hypersensitive to CNDAC and CPT but not to AraC. By contrast, cells lacking PARP1 were only hypersensitive to CPT but not to CNDAC or AraC. Examination of TDP1 expression in the cancer cell line databases (CCLE, GDSC, NCI-60) and human cancers (TCGA) revealed a broad range of expression of TDP1, which was correlated with PARP1 expression, TDP1 gene copy number and promoter methylation. Thus, the present study identifies the importance of TDP1 as a novel determinant of response to CNDAC across various cancer types (especially non-small cell lung cancers), and demonstrates the differential involvement of BRCA2, PARP1 and TDP1 in the cellular responses to CNDAC, AraC and CPT.

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Exploiting radiation-induced signaling to increase the susceptibility of resistant cancer cells to targeted drugs: AKT and mTOR inhibitors as an example

Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival. Analysis of "The Cancer Genome Atlas" (TCGA) database disclosed a significant overexpression of AKT1, AKT2, and MTOR genes in human prostate cancer samples compared with normal prostate gland tissue. Multifractionated radiation of 3D-cultured prostate cancer cell lines with a dose of 2 Gy/day as a clinically relevant schedule resulted in an increased protein phosphorylation and enhanced protein-protein interaction between AKT and mTOR, while gene expression of AKT, MTOR, and related kinases was not altered by radiation. Similar results were found in a xenograft model of prostate cancer. Pharmacological inhibition of mTOR/AKT signaling after activation by multifractionated radiation was more effective than treatment prior to radiotherapy. Taken together, our findings provide a proof-of-concept that targeting signaling molecules after activation by radiotherapy may be a novel and promising treatment strategy for cancers treated with multifractionated radiation regimens such as prostate cancer to increase the sensitivity of tumor cells to molecular targeted drugs.

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MicroRNA-720 regulates E-cadherin-{alpha}E-catenin complex and promotes renal cell carcinoma.

MicroRNAs are implicated in regulating cancer progression and metastasis. Here we show that miR-720 is positively associated with renal cell carcinoma (RCC). Elevated levels of miR-720 were observed in a panel of RCC cell lines and clinical tissues compared to non-malignant cell line and normal samples. Loss of miR-720 function inhibited proliferation, migration and invasion and induced apoptosis in RCC cell lines in vitro and repressed tumor growth in xenograft mouse model. Conversely, gain of miR-720 function in non-malignant HK-2 cells induced pro-cancerous characteristics. Silencing of miR-720 caused a marked induction in the levels of endogenous αE-catenin and E-cadherin protein levels in anti720 transfected cells compared to control. Whereas, miR-720 overexpression in RCC cell lines reduced activity of a luciferase reporter gene fused to the wild-type αE-catenin or E-cadherin 3' UTR compared to non-specific 3' UTR control indicating that αE-catenin-E-cadherin complex is a direct and functional target of miR-720 in RCC. We also observed attenuation of β-Catenin, CD44 and Akt expression in RCC cells transfected with miR-720 inhibitor compared to control. Further, miR-720 exhibited clinical significance in RCC. Expression of miR-720 significantly distinguished malignant from normal samples. Elevated miR-720 levels positively correlated with higher Fuhrman grade, pathological stage and poor overall survival of RCC patients. These findings uncover a new regulatory network in RCC involving metastasis-promoting miR-720 that directly targets expression of key metastasis-suppressing proteins E-cadherin and αE-catenin complex. These results suggest that therapeutic regulation of miR-720 may provide an opportunity to regulate EMT and metastasis in RCC.

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A Systematic Review of Patient-Reported Outcomes for Surgically Amenable Epiphora.

Purpose: In evaluating epiphora and its management, the bottom line for all stakeholders is whether an intervention confers any real benefit on quality of life. A review was conducted to identify and appraise patient-reported outcome measures (PROMs) in surgically amenable epiphora. Methods: A systematic search was conducted of studies relating to surgical intervention for epiphora. Patient-reported outcome measures were identified and assessed against standard criteria. Results: Of 30,544 identified articles, 227 were eligible for data extraction. Of these, 69% reported a PROM as the primary outcome. PROMs identified included single-item symptom scores (48% of primary outcome PROMs), single-item reports of improvement (30%), the Glasgow Benefit Inventory (3%), Lacrimal Symptom Questionnaire (0.5%), Nasolacrimal Duct Obstruction Symptom Score (0.5%), Ocular Surface Disease Index (0.5%), Visual Function Questionnaire-25, the Short Form-36 Health Survey, and 3 other symptom scores. None were developed through consultation with the target population, and there was inadequate testing of content validity. The strengths and limitations of each PROM are presented, with regard to interpretation, responsiveness, reliability, and validity. Discussion: The importance of robust and psychometrically sound PROMs is essential if the under-reporting of quality of life improvement in patients treated for epiphora is to change. Recommendations for the use of each identified PROM are discussed. Conclusions: Several PROMs have been used in the recent literature to evaluate patients undergoing surgery to treat epiphora. Assessed against standard criteria, no PROM has proven to be both psychometrically robust and clinically meaningful for use in this population. Future PROM development should be guided by this standard framework. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Recognition and Management of Acute Dacryocystic Retention.

Purpose: Acute noninfectious dacryocystic retention is an under-recognized condition heralded by painful lacrimal sac swelling, obstruction, and epiphora. This longitudinal chart review aimed to estimate the incidence of this condition in an urban Australian population, while further defining the signs and symptoms of the disease and options for management. Methods: We retrospectively reviewed the charts of 1,593 consecutive patients presenting with acquired nasolacrimal duct obstruction and epiphora between 1990 and 2015. The records of patients with acute dacryocystic retention were analyzed for age, gender, clinical features, and management. Results: Of all patients presenting with nasolacrimal duct obstruction, 20 were found to have acute dacryocystic retention. The mean age was 42.2 +/- 9.3. There was an equal distribution of laterality, and only 2 cases (10%) were bilateral. There was a statistically significant female predominance, and most patients presented reporting 2 to 3 previous episodes. At presentation, 30% of patients reported spontaneous passage of a dacryolith. Despite this, 70% of affected patients required surgical management, with a 64% incidence of stones noted at the time of dacryocystorhinostomy. Conclusions: Acute dacryocystic retention is an uncommon, but even less frequently identified condition, most common in middle-aged women. Improved understanding of this condition and its natural history is likely to enhance patient counseling and avoid ineffective use of antibiotics in affected patients. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Clinical Outcomes in Children With Orbital Cellulitis and Radiographic Globe Tenting.

Purpose: Axial displacement of the globe with tenting centered on the optic nerve-globe junction is a predictor of visual loss in adults. The purpose of this study was to determine the visual outcomes of children with orbital cellulitis and globe tenting. Methods: The records of 46 consecutive children with orbital cellulitis at a single tertiary children's hospital were reviewed retrospectively. Initial and final visual acuities were available for 34 of 46 patients (74%). Globe tenting was defined by an angle of 130[degrees] or less at the optic nerve-globe junction as derived from sagittal CT or MRI. Visual acuities of 4 children with globe tenting (mean age, 10.3 +/- 3.3 years) were compared with those of 30 children without globe tenting (mean age, 10.8 +/- 3.5 years). Final logarithm of the minimum angle of resolution visual acuities were analyzed. Results: The mean posterior globe angle was 124.5[degrees] +/- 8.0[degrees] in patients with globe tenting, compared with 145.6[degrees] +/- 7.4[degrees] in the affected eye of the patients without globe tenting (p = 0.002). Final visual acuity was logarithm of the minimum angle of resolution = 0 following treatment in patients with globe tenting and logarithm of the minimum angle of resolution = 0.02 in patients without tenting (p = 0.70). Discussion: We propose that the increased elastic compliance of the optic nerve sheath and sclera in children may contribute to better visual outcomes. Conclusions: Pediatric orbital cellulitis with globe tenting may not lead to devastating vision loss as previously seen in adults. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Safety Comparison of Laryngeal Mask Use With Endotracheal Intubation in Patients Undergoing Dacryocystorhinostomy Surgery.

Purpose: This study will determine the safety of laryngeal mask airway (LMA) compared with endotracheal tube (ETT) in patients undergoing general anesthesia for dacryocystorhinostomy (DCR) surgery. Methods: In this retrospective cohort study, intraoperative and postoperative outcomes of patients who underwent DCR at UAB Callahan Eye Hospital using either LMA or ETT were compared. Results: Over a period of 52 months, 429 patients underwent external DCR surgery. An ETT was used in 37 patients and LMA in 392 patients. Baseline patient characteristics and anesthetic management were similar. No documented cases of blood or gastric aspiration occurred in the total cohort. Our study confirmed the findings of others that there is less cardiovascular lability on LMA placement than with ETT intubation.1 A 30% increase in heart rate from baseline after intubation (ETT 10.8%, LMA 1.8%; p = 0.010) and after incision (ETT 8.1%, LMA 1.8%; p = 0.047) occurred more frequently in the ETT group. Airway management with an LMA was also less difficult compared with an ETT (ETT 5.7%, LMA 0.5%; p = 0.035). Conclusions: The use of an LMA for airway control is safe and effective in patients undergoing general anesthesia for DCR surgery. No events of aspiration occurred with LMA use. Heart rate increase was significantly less in the LMA group. In our opinion, use of an LMA for airway control during DCR surgery is superior to use of an ETT. Airway protection, improved hemodynamics, and less difficulty in placement of the laryngeal airway device are all validated by this study. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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ESPGHAN Distinguished Service Award 2017 to Professor Olivier Goulet.

No abstract available

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Successful Use of Sirolimus in Children With Large Mesenteric Lymphatic Lesions.

No abstract available

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Response to Letter to the Editor: Bile Acid Replacement in Bile Acid Synthesis Defects.

No abstract available

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Letter regarding “Effect of laser on pain relief and wound healing of recurrent aphthous stomatitis: a systematic review”

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Redirect Health Offers Affordable Healthcare Alternative to Drive Forward Small Businesses

Redirect Health makes healthcare a smart advantage for businesses, allowing them to easily and affordably recruit and retain employees in a way their competitors cannot. They believe America is driven forward by small businesses – the people who work for them, and the families who rely on them to be successful.

Today, the healthcare experience isn't always that great. In fact, it can be downright daunting and overwhelming to navigate. Getting the care they need when they want it is getting more and more difficult. The mission of Redirect Health is to help employers create healthcare plans that are affordable, comply with Obamacare and take great care of their people.

The American Sleep and Breathing Academy (ASBA) CEO, David Gergen, said Redirect Health saved his business thousands of dollars. With over 80 employees at Gergen's Sleep Appliance Lab and Gergen's Orthodontic Lab, his health care costs were reduced by over half of what they were prior. In turn, he spread the news and many dentists are now turning to Redirect Health for their healthcare solutions.

To learn more about Redirect Health, visit RedirectHealth.com

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Hyaluronan-mediated mononuclear leukocyte binding to gingival fibroblasts

Abstract

Objectives

Binding of mononuclear leukocytes to hyaluronan cable structures is a well-known pathomechanism in several chronic inflammatory diseases, but has not yet described for chronic oral inflammations. The aim of this study was to evaluate if and how binding of mononuclear leukocytes to pathologic hyaluronan cable structures can be induced in human gingival fibroblasts.

Material and methods

Experiments were performed with human gingival fibroblasts and peripheral blood mononuclear cells (PBMCs) from three healthy blood donors. Gingival fibroblasts were stimulated with (1) tunicamycin, (2) polyinosinic/polycytidylic acid (Poly:IC), and (3) lipopolysaccharides (LPS) to simulate (1) ER stress and (2) viral and (3) bacterial infections, respectively. Fibroblasts were then co-incubated with PBMCs, and the number of bound and fluorescently labeled PBMCs was assessed using a fluorescence reader and microscopy. For data analysis, a linear mixed model was used.

Results

Hyaluronan-mediated binding of PBMCs to gingival fibroblasts was increased by tunicamycin and Poly(I:C) but not by LPS. Hyaluronidase treatment and co-incubation with hyaluronan transport inhibitors reduced this binding.

Conclusions

Results suggest that hyaluronan-mediated binding of blood cells might play a role in oral inflammations. A potential superior role of viruses needs to be confirmed in further clinical studies.

Clinical relevance

The linkage between pathological hyaluronan matrices and oral infections opens up potential applications of hyaluronan transport inhibitors in the treatment of chronic oral inflammations.

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Anticancer drugs and the regulation of Hedgehog genes GLI1 and PTCH1, a comparative study in nonmelanoma skin cancer cell lines.

Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin cancer for their therapeutic potential in localized, enhanced topical treatment of SCC and BCC. Cytotoxicity profiles for vismodegib, 5-fluorouracil (5-FU), methotrexate (MTX), cisplatin, bleomycin, and vorinostat were established in terms of half maximal inhibitory concentration values in a panel of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines. The impact of treatment on the regulation of Hedgehog pathway target genes (GLI1 and PTCH1), measured by real-time PCR, was compared between UWBCC1 and HaCaT. Varying cell line sensitivity profiles to the examined anticancer drugs were observed. Generally, 24-h drug exposure was sufficient to reduce cell viability. We found that 5-FU, MTX, and cisplatin significantly downregulated the expression of two genes controlled by the Hedgehog pathway (

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Hyaluronan-mediated mononuclear leukocyte binding to gingival fibroblasts

Abstract

Objectives

Binding of mononuclear leukocytes to hyaluronan cable structures is a well-known pathomechanism in several chronic inflammatory diseases, but has not yet described for chronic oral inflammations. The aim of this study was to evaluate if and how binding of mononuclear leukocytes to pathologic hyaluronan cable structures can be induced in human gingival fibroblasts.

Material and methods

Experiments were performed with human gingival fibroblasts and peripheral blood mononuclear cells (PBMCs) from three healthy blood donors. Gingival fibroblasts were stimulated with (1) tunicamycin, (2) polyinosinic/polycytidylic acid (Poly:IC), and (3) lipopolysaccharides (LPS) to simulate (1) ER stress and (2) viral and (3) bacterial infections, respectively. Fibroblasts were then co-incubated with PBMCs, and the number of bound and fluorescently labeled PBMCs was assessed using a fluorescence reader and microscopy. For data analysis, a linear mixed model was used.

Results

Hyaluronan-mediated binding of PBMCs to gingival fibroblasts was increased by tunicamycin and Poly(I:C) but not by LPS. Hyaluronidase treatment and co-incubation with hyaluronan transport inhibitors reduced this binding.

Conclusions

Results suggest that hyaluronan-mediated binding of blood cells might play a role in oral inflammations. A potential superior role of viruses needs to be confirmed in further clinical studies.

Clinical relevance

The linkage between pathological hyaluronan matrices and oral infections opens up potential applications of hyaluronan transport inhibitors in the treatment of chronic oral inflammations.

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Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials

Elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the...

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Randomized controlled trial of EndoWrist-enabled robotic versus human laparoendoscopic single-site access surgery (LESS) in the porcine model

Abstract

Introduction

A robotic laparoendoscopic single-site access surgery (R-LESS) platform that incorporates the EndoWrist function of robotic instruments may provide better triangulation and retraction during LESS. The aim of the study is to assess if R-LESS is feasible with standard robotic instruments via a single incision and whether the approach could reduce the difficulty of the procedure and confer additional benefits over conventional LESS.

Methods

This was a prospective randomized controlled study investigating the workload performance, efficacy, and risks of performing R-LESS when compared with human LESS (H-LESS) in a survival porcine model for cholecystectomy and gastrojejunostomy. The primary outcome is the NASA task load index. Secondary outcomes included the difficulty of the procedures, procedural time, morbidities, and mortalities.

Results

Twenty-four cholecystectomies and gastrojejunostomies using the R-LESS or H-LESS approach (12:12) were performed. None of the swine suffered from procedural adverse events and none of the procedures required conversion. In both the cholecystectomy and gastrojejunostomy groups, R-LESS was associated with significantly lower NASA task load index (P < 0.001) and reduced difficulties in various steps of the procedures. No differences in the overall procedure times of the two procedures were observed (P = 0.315).

Conclusion

The R-LESS approach significantly reduced the workload and difficulties of LESS cholecystectomies and gastrojejunostomies. A dedicated single-site platform that could reduce instrument clashing while retaining the EndoWrist function is eagerly awaited.

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Advances in closed-loop deep brain stimulation devices

Millions of patients around the world are affected by neurological and psychiatric disorders. Deep brain stimulation (DBS) is a device-based therapy that could have fewer side-effects and higher efficiencies i...

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Dermoid Cyst of the Prepontine Cistern and Meckel's Cave: Illustrative Case and Systematic Review

J Neurol Surg B
DOI: 10.1055/s-0037-1604332

Objective Dermoid cysts are benign, congenital malformations that account for ∼0.5% of intracranial neoplasms. The authors describe a 42-year-old female with a prepontine dermoid cyst who underwent apparent gross total resection (GTR) but experienced cyst recurrence. To date, very few cases of prepontine dermoid cysts have been reported. The prevalent region where these cysts are located can be difficult to determine. In addition, the authors systematically review the literature to characterize the clinical presentation, anatomical distribution, and surgical outcomes of intracranial dermoid cysts. Design Systematic review. Setting/Participants PubMed, Web of Science, and Scopus databases. Main Outcome Measures Extent of resection, symptom improvement, and recurrence rates. Results A total of 69 patients with intracranial dermoid cysts were identified. Three (4.3%) intracranial dermoid cysts were located in the prepontine cistern. The average age of patients was 33.3 years. The most common presenting symptoms were headache (52.2%) and visual disturbances (33.3%). Intracranial dermoid cysts were distributed similarly throughout the anterior, middle, and posterior cranial fossae (29.0%, 36.2%, and 29.0%, respectively). GTR was achieved in 42.0% of cases. Thirty-four (49.3%) patients experienced symptom resolution. Recurrence rate was 5.8% at a mean follow-up of 2.1 years. Conclusions Intracranial dermoid cysts most often present as headaches and visual disturbances. Intracranial dermoid cysts were found in the anterior, middle, and posterior cranial fossae at similar frequencies but with clear predilections for the Sylvian fissure, sellar region, and cerebellar vermis. Outcomes following surgical excision of intracranial dermoid cysts are generally favorable despite moderate rates of GTR.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Focal Increased Tc-99m MDP Uptake in the Nutrient Foramen of the Femoral Diaphysis on Bone SPECT/CT

Abstract

We present images of an 83-year-old female with a history of osteoporosis and bilateral total knee replacement arthroplasty, referred for bone scintigraphy and single-photon emission computed tomography (SPECT)/computed tomography (CT), owing to left knee pain. No trauma to, or intense exercise of, the knee was reported. The bone scan and SPECT/CT revealed a focally increased Tc-99m methylene diphosphonate (MDP) uptake in the medial cortex of the left femoral diaphysis with matched linear radiolucency on CT images. This was misinterpreted as atypical femoral stress fracture; however, focal stress reaction injury to the nutrient foramen was confirmed on contrast-enhanced magnetic resonance imaging.

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How do red and infrared low-level lasers affect folliculogenesis cycle in rat’s ovary tissue in comparison with clomiphene under in vivo condition

Abstract

Folliculogenesis is a cycle that produces the majority of oocyte. Any disruption to this cycle leads to ovulation diseases, like polycystic ovarian syndrome (PCOS). Treatments include drugs and surgery; lasers have also been used complementarily. Meanwhile, still there is no definite treatment for PCOS. This study investigated the photo-bio stimulation effect of near-infrared and red low-level laser on producing follicles and compared the result with result of using common drug, clomiphene. Therefore, the aim of this study was to propose the use of lasers autonomously treatment. So, there was one question: how do lasers affect folliculogenesis cycle in rat's ovary tissue? In this study, 28 rats were assigned to four groups as follows: control (CT), clomiphene drug (D), red laser (RL), and near-infrared laser (NIRL). Afterwards, 14 rats of RL and NIRL groups received laser on the first 2 days of estrous cycle, each 6 days, for 48 days. During treatment period, each rat received energy density of 5 J/cm². Seven rats in D group received clomiphene. After the experiment, lasers' effects at two wavelengths of 630 and 810 nm groups have been investigated and compared with clomiphene and CT groups. Producing different follicles to complement folliculogenesis cycle increased in NIRL and RL groups, but this increase was significant only in the NIRL group. This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS.

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Dysphagia and Speech-Language Pathology Involvement Following Chemical Ingestion Injury: A Review of 44 Cases Admitted to a Quaternary Australian Hospital (2008–2012)

Purpose

This study aimed to explore the clinical characteristics of an adult chemical ingestion population and examine the course of return to oral intake post injury and speech-language pathologist (SLP) involvement during the initial acute-care admission.

Method

A retrospective chart review of adults admitted to a quaternary hospital for the treatment of an acute chemical ingestion injury between 2008 and 2012 was conducted.

Results

Forty-four adults (23 men, 21 women) were identified as receiving treatment for ingestion injury, of whom 18 (40.91%) required altered oral intake. Of those requiring altered oral intake, 50% were referred to SLPs. Individuals requiring altered oral intake were significantly (p < .05) older, more likely to be men, and present with more severe injuries requiring longer ICU and hospital admissions following intentional chemical ingestions than those who were able to commence a normal oral diet without any alteration or nonoral supplementation. By discharge, 15.91% (n = 7) of the total cohort had not resumed normal oral intake.

Conclusions

Return to oral intake post chemical ingestion injury can be protracted and complex. Referrals to SLPs were limited. These data may aid prognostic insight as well as provide (a) collateral information to assist discharge planning and follow-up and (b) background for evaluating the potential for SLP involvement.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJSLP-16-0075/2648978/Dysphagia-and-SpeechLanguage-Pathology-Involvement

First US Transgender Surgery, Psychiatry Fellowships

In answer to growing treatment disparities and lack of knowledge by clinicians, the Mount Sinai Health System has launched two first-of-their-kind transgender medical fellowships.
Medscape Medical News

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Opioid Prescribing Behavior After Elective Surgery Varies Widely

Reuters Health Information

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Optimaler Resektionsrand für die brusterhaltende Operation und Ganzbrustbestrahlung beim duktalen Carcinoma in situ

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Feasibility and diagnostic accuracy of point-of-care handheld echocardiography in acute ischemic stroke patients – a pilot study

Standard echocardiography (SE) is an essential part of the routine diagnostic work-up after ischemic stroke (IS) and also serves for research purposes. However, access to SE is often limited. We aimed to asses...

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Erosión ósea del canal carotídeo. Síndrome de Gradénigo

Publication date: Available online 10 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Aina Brunet-Garcia, M. Virginia Barrios-Crispi, Marta Faubel-Serra




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Evaluación de la capacidad formativa del libro del residente de Otorrinolaringología español (FORMIR) como portafolio electrónico

Publication date: Available online 10 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Juan Manuel Maza Solano, Gustavo Benavente Bermudo, Francisco José Estrada Molina, Jesús Ambrosiani Fernández, Serafín Sánchez Gómez
Introducción y objetivosEvaluar la capacidad formativa del libro del residente español como portafolio electrónico para alcanzar los objetivos de aprendizaje de los MIR de Otorrinolaringología (ORL).MétodosSe realizó una investigación cualitativa multimétodo de características tranversal, temporal y de orientación retrospectiva sobre los MIR de ORL mediante un cuestionario estructurado y una entrevista semiestructurada, sobre la aplicación informática web FORMIR.ResultadosParticiparon el 56,5% de los MIR de ORL de alguno de los 63 hospitales españoles acreditados para impartir formación en ORL entre 2009 y 2012. Los resultados obtenidos demostraron que los MIR de ORL que utilizaban el portafolio electrónico eran capaces de autoguiar mejor su aprendizaje, conocían mejor sus objetivos de aprendizaje, cumplían más eficientemente el programa de formación, identificaban más claramente las causas de sus carencias en el aprendizaje y consideraban que FORMIR como portafolio electrónico constituía una herramienta formativa idónea para sustituir al libro del residente en formato papel.ConclusionesLos MIR de ORL apreciaban de forma muy relevante las prestaciones formativas de FORMIR como portafolio electrónico, especialmente su interfaz, el feedback numérico y automático sobre la adquisición de competencias, su capacidad de almacenamiento de evidencias y su capacidad de visualizarse como logbook de la Unión Europea de Médicos Especialistas o como un curriculum vitae estándar. Este feedback automático facilita el aprendizaje autoguiado. Todo esto hace de FORMIR una herramienta formativa y evaluativa que supera las prestaciones y aceptación de instrumentos similares puestos a disposición de los residentes, que no dudan en proponerlo como el libro del residente más idóneo para facilitar su formación especializada.Backgroundand objectives We have evaluated the training capacity of the Spanish resident training book as an electronic portfolio to achieve the learning objectives of otorhinolaryngology (ENT) residents.MethodsA multi-method qualitative investigation with transversal characteristics, temporal and retrospective guidance was performed on Spanish ENT residents using a structured questionnaire, a semi-structured interview, and a computer application on the FORMIR website.ResultsA 56.5% of ENT-residents specialising in one of the 63 accredited Spanish hospitals between 2009-2012 participated in the study. The results obtained show that the ENT residents who used the e-portfolio were better able to implement self-guided study, were more aware of their learning objectives, fulfilled the training programme more efficiently, identified the causes of learning gaps more clearly, and considered FORMIR in e-portfolio format to be an ideal training tool to replace the resident training book in paper format.ConclusionsThe ENT residents greatly appreciated the training benefits of FORMIR as an e-portfolio, especially its simple and intuitive interface, the ease and comfort with which they could record their activities, the automatic and numeric feedback on the acquisition of their competencies (which facilitates self-guided learning), its storage capacity for evidence, and its ability to be used as UEMS logbook as well as a standard curriculum vitae. All these features make FORMIR a training and evaluation tool that outperforms similar instruments available to ENT residents. They do not hesitate to identify it as the ideal resident training book for facilitating their specialised training.



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Arteria lusoria: A rare cause of tracheal compression

Publication date: Available online 10 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Ana Nóbrega-Pinto, Isabel Carvalho, Cecília Almeida-Sousa




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Seudotumor inflamatorio subglótico en un niño de 3 años

Publication date: Available online 10 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Javier Cervera Escario, Sara Sirvent Cerdá, Saturnino Santos Santos, Adolfo Sequeiros González




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Primary tuberculosis of the nasal septum: The non-ulcerated form presenting as septal thickening

Publication date: Available online 10 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Neeraj Aggarwal, Mainak Dutta, Ramanuj Sinha




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Neurocognitive sparing of desktop microbeam irradiation

Normal tissue toxicity is the dose-limiting side effect of radiotherapy. Spatial fractionation irradiation techniques, like microbeam radiotherapy (MRT), have shown promising results in sparing the normal brai...

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New study reports benefits of dental therapists’ care

In the first long-term study of dental therapist utilization, University of Washington researchers have found that greater access to the therapists' services in Alaska resulted in more use of preventive dental services and fewer extractions among adults and children.

The post New study reports benefits of dental therapists' care appeared first on UW School of Dentistry.

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Prospective Evaluation of the Relationship Between Mechanical Stability and Response to Palliative Radiotherapy for Symptomatic Spinal Metastases

AbstractBackground.A substantial number of patients with spinal metastases experience no treatment effect from palliative radiotherapy. Mechanical spinal instability, due to metastatic disease, could be associated with failed pain control following radiotherapy. This study investigates the relationship between the degree of spinal instability, as defined by the Spinal Instability Neoplastic Score (SINS), and response to radiotherapy in patients with symptomatic spinal metastases in a multi‐institutional cohort.Methods and Materials.The SINS of 155 patients with painful thoracic, lumbar, or lumbosacral metastases from two tertiary hospitals was calculated using images from radiotherapy planning CT scans. Patient‐reported pain response, available for 124 patients, was prospectively assessed. Pain response was categorized, according to international guidelines, as complete, partial, indeterminate, or progression of pain. The association between SINS and pain response was estimated by multivariable logistic regression analysis, correcting for predetermined clinical variables.Results.Of the 124 patients, 16 patients experienced a complete response and 65 patients experienced a partial response. Spinal Instability Neoplastic Score was associated with a complete pain response (adjusted odds‐radio [ORadj] 0.78; 95% confidence interval [CI] 0.62–0.98), but not with an overall pain response (ORadj 0.94; 95% CI 0.81–1.10).Conclusions.A lower SINS, indicating spinal stability, is associated with a complete pain response to radiotherapy. This supports the hypothesis that pain resulting from mechanical spinal instability responds less well to radiotherapy compared with pain from local tumor activity. No association could be determined between SINS and an overall pain response, which might indicate that this referral tool is not yet optimal for prediction of treatment outcome.Implications for Practice.Patients with stable painful spinal metastases, as indicated by a Spinal Instability Neoplastic Score (SINS) of 6 or lower, can effectively be treated with palliative external beam radiotherapy. The majority of patients with (impending) spinal instability, as indicated by a SINS score of 7 or higher, will achieve a (partial) response after palliative radiotherapy; however, some patients might require surgical intervention. Therefore, it is recommended to refer patients with a SINS score of 7 or higher to a spine surgeon to evaluate the need for surgical intervention.

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Robert L. Comis: In Memoriam

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Curative, Life‐Extending, and Palliative Chemotherapy: New Outcomes Need New Names

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Data Linkage to Improve Geriatric Oncology Research: A Feasibility Study

AbstractOlder adults (aged 65 years and older) diagnosed with cancer account for most cancer‐related morbidity and mortality in the United States but are often underrepresented on clinical trials. Recent attention from a variety of professional, research, regulatory, and patient advocacy groups has centered on data linkage and data sharing as a means to capture patient information and outcomes outside of clinical trials to accelerate progress in the fight against cancer. The development of a more robust observational research data infrastructure would help to address gaps in the evidence base regarding optimal approaches to treating cancer among the growing and complex population of older adults. To demonstrate the feasibility of building such a resource, we linked information from a sample of older adults with cancer in North Carolina using three distinct, but complementary, data sources: (a) the Carolina Senior Registry, (b) the North Carolina Central Cancer Registry, and (c) North Carolina fee‐for‐service Medicare claims data. A description of the linkage process, metrics, and characteristics of the final cohort is reported. This study highlights the potential for data linkage to improve the characterization of health status among older adults with cancer and the possibility to conduct passive follow‐up for outcomes of interest over time. Extensions of these linkage efforts in partnership with other institutions will enhance our ability to generate evidence that can inform the management of older adults with cancer.

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Prolonged Pemetrexed Infusion Plus Gemcitabine in Refractory Metastatic Colorectal Cancer: Preclinical Rationale and Phase II Study Results

AbstractLessons Learned. Difficulties in translating in vitro results into clinical practice are inevitable.Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged.Background.We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48‐hour wash‐out and then gemcitabine. This combination was then advanced to a phase II clinical trial.Methods.Patients with metastatic colorectal cancer in progression after standard treatment were included in the study. Adequate bone marrow reserve, normal hepatic and renal function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 were required. Treatment consisted of an 8‐hour intravenous infusion of pemetrexed 150 mg/m2 on day 1 and a 30‐minute intravenous infusion of gemcitabine 1,000 mg/m2 on day 3 of each cycle, repeated every 14 days.Results.Fourteen patients were enrolled onto the study (first step). No objective responses were seen, and evidence of stable disease was observed in only one of the 12 evaluable patients. The most important grade 3–4 side effects were hematological toxicity (neutropenia 64.2%, thrombocytopenia 71.4%, anemia 28.7%), fatigue (50.0%), and stomatitis (21.5%). Median overall survival and time to progression were 5.8 months (95% confidence interval [CI]: 3.9–7.1) and 2.1 months (95% CI: 1.7–2.8), respectively.Conclusion.The experimental pemetrexed‐gemcitabine combination proved to be inactive and moderately toxic.

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Health Care Resource Utilization and Associated Costs Among Metastatic Cutaneous Melanoma Patients Treated with Ipilimumab (INTUITION Study)

AbstractBackground.There are limited real‐world data on health care resource utilization (HCRU) among advanced melanoma patients. The objective of this study was to describe HCRU and health care costs associated with the management of advanced melanoma patients receiving ipilimumab.Methods.This retrospective multinational, observational study included advanced melanoma patients from Australia, Germany, Italy, and Spain who had received at least 1 dose of ipilimumab. Data extracted from medical charts included inpatient admissions, outpatient visits, surgical procedures, laboratory investigations, radiation therapy, imaging studies, and concomitant medications. Cost estimates were based on unit costs from country‐specific standard reimbursement sources. Subgroup analyses were performed for BRAF mutation status and ipilimumab refractory patients, who had disease progression within 24 weeks of their last dose of ipilimumab.Results.Mean age of 362 enrolled patients was 60.6 years (standard deviation [SD] 14.4). During a median follow‐up period of 30.2 weeks, 57% of patients were admitted to hospital and 16% underwent surgery. Health care resource utilization rates varied substantially across countries and were highest in Germany. Concomitant medications to treat adverse events were commonly used. Subgroup analyses showed higher utilization rates among ipilimumab refractory and BRAF mutant patients. Mean weekly total costs associated with HCRU were lower in the pre‐progression period (€107; 95% confidence interval (CI): 79–145) than in the post‐progression period (€216; 95% CI: 180–259).Conclusion.Health care resource utilization pattern and associated costs among patients treated with ipilimumab varied greatly among countries and between pre‐ and post‐progression periods. There is a high economic burden associated with ipilimumab refractory melanoma.Implications for Practice.Metastatic melanoma patients treated with the anti‐CTLA‐4 inhibitor ipilimumab have a high utilization of various types of health care services, such as inpatient hospital stays or doctor visits. There are differences across countries regarding patterns of health care utilization and economic burden of the disease. Health care services are used more frequently after patients experience progression of their disease. The study highlights that better therapies leading to durable response in patients with metastatic melanoma have the potential to decrease health care costs and patient burden in terms of hospitalizations and other health care services.

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