FOLFOX activity in a rare case of metastatic colonic adenocarcinoma of the tongue: a case report

Abstract

Background

Adenocarcinomas of the oral cavity are rare neoplasms, and only four cases of primary colonic adenocarcinoma of the tongue have ever been described in literature. Very few information about chemotherapy sensitiveness of this type of neoplasia is available, with only one regimen that showed some activity in a metastatic patient.

Case presentation

We describe the case of a patient bearing a metastatic colonic adenocarcinoma of the tongue submitted to a first-line chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX regimen). After chemotherapy the patient obtained the complete disappearance of the primitive neoplasia located in the body of the tongue, and a tumor size reduction > 50% of liver and lung metastases.

Conclusions

This case demonstrated the activity of the combination of oxaliplatin and 5-fluorouracil in this very rare neoplasia. The FOLFOX regimen might be considered either in advanced and especially in the neoadjuvant setting, when the reduction of the primary tumor is highly needed.

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Genetic correction of serum AFP level improves risk prediction of primary hepatocellular carcinoma in the Dongfeng–Tongji cohort study

Cancer Medicine, EarlyView.


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Efficacy of two types of palliative sedation therapy defined using intervention protocols: proportional vs. deep sedation

Abstract

Purpose

This study investigated the effect of two types of palliative sedation defined using intervention protocols: proportional and deep sedation.

Methods

We retrospectively analyzed prospectively recorded data of consecutive cancer patients who received the continuous infusion of midazolam in a palliative care unit. Attending physicians chose the sedation protocol based on each patient's wish, symptom severity, prognosis, and refractoriness of suffering. The primary endpoint was a treatment goal achievement at 4 h: in proportional sedation, the achievement of symptom relief (Support Team Assessment Schedule (STAS) ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale (RASS) ≤ 0) and in deep sedation, the achievement of deep sedation (RASS ≤ − 4). Secondary endpoints included mean scores of STAS and RASS, deep sedation as a result, and adverse events.

Results

Among 398 patients who died during the period, 32 received proportional and 18 received deep sedation. The treatment goal achievement rate was 68.8% (22/32, 95% confidence interval 52.7–84.9) in the proportional sedation group vs. 83.3% (15/18, 66.1–100) in the deep sedation group. STAS decreased from 3.8 to 0.8 with proportional sedation at 4 h vs. 3.7 to 0.3 with deep sedation; RASS decreased from + 1.2 to − 1.7 vs. + 1.4 to − 3.7, respectively. Deep sedation was needed as a result in 31.3% (10/32) of the proportional sedation group. No fatal events that were considered as probably or definitely related to the intervention occurred.

Conclusion

The two types of intervention protocol well reflected the treatment intention and expected outcomes. Further, large-scale cohort studies are promising.

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Predictors of analgesic efficacy of neurolytic celiac plexus block in patients with unresectable pancreatic cancer: the importance of timing

Abstract

Background

Neurolytic celiac plexus block (NCPB) is a safe and effective method for reducing abdominal cancer pain. However, the analgesic efficacy of NCPB is not always guaranteed. The aim of this retrospective study was to identify predictors for the analgesic efficacy of NCPB in patients with unresectable pancreatic cancer.

Methods

Patients with unresectable pancreatic cancer who underwent NCPB from 2006 to 2015 were enrolled. Good analgesia after NCPB was defined as ≥ 50% reduction in pain score at day 30. Patient demographics, cancer characteristics, and pain-related factors were evaluated using a logistic regression analysis to identify predictors for good analgesia after NCPB. Additionally, survival outcomes were compared between patients with poor and good analgesia after NCPB.

Results

A total of 112 patients satisfied the study protocol requirements. Forty-seven patients (41.9%) showed good analgesia after NCPB. Better performance status, lower serum CA 19-9 level, shorter pain duration, and lower opioid dose were observed in patients with good analgesia after NCPB. Good performance status (ECOG performance status 1 vs. 2 or 3, OR = 2.737, 95% CI = 1.149 to 6.518, P = 0.023) and low daily opioid use (< 150 vs. ≥ 150 mg, OR = 2.813, 95% CI = 1.159 to 6.831, P = 0.022) before NCPB were independent predictors of good analgesia after NCPB. The median survival was significantly lower for patients with poor analgesia after NCPB (68 vs. 150 days, P < 0.001).

Conclusion

NCPB should be offered early to selected patients to improve its analgesic efficacy in advance of deterioration from disease and pain in this population.

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Sexual health in patients with hematological malignancies: a neglected issue

Abstract

Current evidence, although limited, outlines that sexual dysfunction may represent a prominent part of the symptom burden experienced by the patients with hematologic malignancies (HM). However, despite their presumed negative effects on quality of life (QoL), sexual health is not typically considered in the QoL assessment of HM patients. In addition, very few studies have been conducted in this area. Therefore, it would be important to further investigate how newer drugs developed in recent years for patients with HM, including targeted therapies and impact on sexual health, and how this influence overall patients' QoL outcomes.

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The views of patients with metastatic prostate cancer towards physical activity: a qualitative exploration

Abstract

Purpose

Patients with metastatic cancer can experience debilitating symptoms, which may influence attitudes towards and engagement in physical activity. This study aimed to examine the attitudes of patients living with metastatic prostate cancer towards physical activity.

Materials and methods

Semi-structured interviews were completed with male patients living with metastatic prostate cancer. Interviews included eight questions related to patients' attitudes towards physical activity. Content analysis was conducted on the transcribed interview data. Twenty men with metastatic prostate cancer (mean age 71 ± 8.5 years; body mass index 30.19 ± 5.37 kg/cm²) and associated bone metastases (55% with > 2 regions affected) participated in the study.

Results

Men's views towards physical activity were coded into the following major themes: (1) barriers to physical activity, (2) benefits of physical activity, (3) a reduction in physical activity levels post diagnosis and (4) social support for physical activity. Symptoms of metastatic prostate cancer and treatment side effects including pain and fatigue negatively influenced activity participation. In addition, many generic barriers to physical activity were described such as bad weather and a lack of suitable facilities for exercising in rural areas.

Conclusion

Men living with metastatic prostate cancer have unique needs regarding physical activity related to symptoms of both their cancer and cancer treatment. There is a need to increase prompts that encourage those with metastatic prostate cancer to maintain/increase physical activity levels post diagnosis. Given the individualised needs of this patient group, referral to a cancer exercise specialist should be considered for prescription of tailored physical activity programmes.

Trial registration

Clinicaltrials.gov NLM Identifier: NCT02453139

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Chemotherapy-induced nausea and vomiting (CINV) in patients with advanced lung cancer during the first-line treatment: assessment by physicians, nurses, and patients from an Italian multicenter survey

Abstract

Purpose

Chemotherapy-induced nausea and vomiting (CINV) still represents a common side-effect of chemotherapy, and often, its perception differs between patients and healthcare professionals. The aim of this study was to evaluate the agreement on the perception of CINV and other items among clinicians, patients, and nurses.

Methods

This observational prospective study was part of an evaluation program promoted by the Women Against Lung Cancer in Europe (WALCE) Onlus. From August 2015 to February 2016, a survey was administered in 11 oncologic institutions to 188 stage IV lung cancer patients and to their oncologists and nurses during first-line chemotherapy. Our survey investigated 11 aspects: anxiety, mood, weakness, appetite, nausea, vomiting, pain, drowsiness, breath, general condition, and trust in treatments. These items were assessed through Numerical Rating Scale at four consecutive evaluations: at T0 (immediately prior to the first cycle), at T1 (immediately prior to the second cycle), at T2 (immediately prior to the third cycle), and at T3 (immediately prior to the fourth cycle). Clinician versus patient (CvP), nurse versus patient (NvP), and clinician versus nurse (CvN) agreements were estimated applying Weighted Cohen's kappa. A multivariate logistic model and generalized equation estimates were applied to evaluate factors possibly influencing CINV development.

Results

The incidence of patients reporting CINV varied from 40% at T0 to 71% at T3. Both CvP and NvP agreement on the investigated items were mainly moderate, slightly increasing over time, and becoming substantial for some items, in particular for NvP. Pre-chemotherapy anxiety in its mild, moderate, and severe manifestations, as well as mild, moderate, and severe anxiety experienced after chemotherapy start, exposed patients to a higher risk of anticipatory and acute/delayed CINV, respectively.

Conclusions

Despite clinical staff awareness of patients' status and perceptions, CINV still represents a clinical problem. This study confirms that particular attention should be paid to anxiety due to its key role in CINV development.

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Associations among physical symptoms, fear of cancer recurrence, and emotional well-being among Chinese American breast cancer survivors: a path model

Abstract

Purpose

Most existing studies on fear of cancer recurrence (FCR) are exploratory without theoretical underpinnings and have been conducted among non-Hispanic Whites. Based on theoretical models, we hypothesized that more physical symptoms (pain and fatigue) would be associated with higher FCR, which, in turn would be related to lower emotional well-being among Chinese American breast cancer survivors.

Methods

Participants were 77 Chinese American women who were diagnosed with breast cancer of stages 0–III. A cross-sectional path analysis was conducted with a bootstrapping method.

Results

The final model showed that indirect paths from pain interference to emotional well-being and from fatigue to emotional well-being via FCR were significant. That is, higher levels of pain interference and fatigue were associated with higher FCR, which was further related to lower emotional well-being.

Conclusions

To our best knowledge, this is the first theory-driven study that investigates FCR experiences among Chinese American breast cancer survivors. Our study might provide a more comprehensive understanding of FCR as it simultaneously shows predictors and a psychological consequence of FCR. Results need to be replicated in large, racially/ethnically diverse samples and longitudinal studies.

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Bismuth adjuvant and adverse effects of chemotherapy: issues with statistical analyses

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Vitamin “G”arden: a qualitative study exploring perception/s of horticultural therapy on a palliative care ward

Abstract

Purpose

In a palliative care setting, the preservation of quality of life is of particular importance. Horticultural therapy (HT) is reported as an excellent way to improve physical as well as psychological well-being, reduce levels of anxiety and depression, and promote social interaction. The use of horticultural interventions in palliative care has not yet been explored. The aim of this study was to explore the effects of HT in patients and team members on a palliative care ward.

Methods

This study was based on a qualitative methodology, comprising 20 semistructured interviews with 15 advanced cancer patients participating in HT and with 5 members of the palliative care team. Interviews were analyzed using NVivo 10 software based on thematic analysis.

Results

The results revealed the following themes: (1) well-being, (2) variation of clinical routine, (3) creation, and (4) building relationships. Patients experienced positive stimulation through HT, were distracted from daily clinical routines, enjoyed creative work, and were able to build relationships with other patients. HT was also welcomed by the members of the palliative care team. Thirty-six percent of the patients did not meet the inclusion criteria, and 45% could not participate in the second or third HT session.

Conclusions

Our study showed that the availability of HT was highly appreciated by the patients as well as by the palliative care team. Nevertheless, the dropout rate was high, and therefore, it might be more feasible to integrate green spaces into palliative care wards.

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Administrating docetaxel, doxorubicin, and cyclophosphamide as a neoadjuvant treatment may decrease lymphedema risk in breast cancer patients

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Diagnostic-driven antifungal approach in neutropenic patients at high risk for chronic disseminated candidiasis: preliminary observations on the role of 1,3-β-D-glucan antigenemia and multiphasic contrast-enhanced computed tomography

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Sleep disturbance among Chinese breast cancer survivors living in the USA

Abstract

Purpose

Emerging evidence suggests Chinese breast cancer survivors, a largely understudied population, are at increased risk of sleep disturbance which can have significant impacts on quality of life and other important outcomes. This study aims to describe sleep disturbance among Chinese breast cancer survivors and to examine demographic and clinical correlates as well as psychosocial correlates of sleep disturbance.

Methods

Data from 80 Chinese breast cancer survivors in the USA completed the Chinese version of the Pittsburgh Sleep Quality Index as well as measures of quality of life, depressive symptoms, and perceived stress. Participants also completed measures of demographic factors and acculturation.

Results

Two thirds (66%) of survivors experienced elevated sleep disturbance. Approximately half (49%) reported sleep efficiency, the percentage of time in bed that is spent asleep, that was below the recommended cutoff. Compared to those without sleep disturbance, those with sleep disturbance had worse quality of life, more depressive symptoms, and more perceived stress (ps ≤ .01).

Conclusions

This study is among the first to examine sleep disturbance among any Asian cancer population in the USA. Findings indicate Chinese breast cancer survivors may experience significant disparities in sleep disturbance relative to non-Hispanic Whites and suggest an urgent need for interventions to address sleep disturbance among Chinese breast cancer survivors.

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Transfusion practice patterns in patients with anemia receiving myelosuppressive chemotherapy for nonmyeloid cancer: results from a prospective observational study

Abstract

Purpose

The decision to prescribe packed red blood cell (PRBC) transfusions in patients with chemotherapy-induced anemia (CIA) includes assessment of clinical features such as the patient's cancer type and treatment regimen, severity of anemia symptoms, and presence of comorbidities. We examined contemporary transfusion practices in patients with nonmyeloid cancer and CIA.

Methods

Key inclusion criteria were age ≥ 18 years with nonmyeloid cancer, receiving first/second-line myelosuppressive chemotherapy, baseline hemoglobin (Hb) ≤ 10.0 g/dL, and planned to receive ≥ 1 PRBC transfusions. Exclusion criteria were receipt of erythropoiesis-stimulating agents within 8 weeks of screening and/or chronic renal insufficiency. Data were collected from patients' medical records, laboratory values, and physician/provider questionnaires. Proportion of patients for each clinical consideration leading to a decision to prescribe a PRBC transfusion and 95% exact binomial confidence intervals were determined.

Results

The study enrolled 154 patients at 18 sites in USA; 147 (95.5%) received a PRBC transfusion. Fatigue was the most common symptom affecting the decision to prescribe a PRBC transfusion (101 [69.2%] patients). Of the three reasons selected as primary considerations for prescribing a PRBC transfusion, anemia symptoms (106 [72.1%] patients) was the most frequently reported, followed by Hb value (37 [25.2%] patients) and medical history (4 [2.7%] patients).

Conclusions

In this study, the primary consideration for prescribing a PRBC transfusion was anemia symptoms in 72.1% of patients, with only 25.2% of patients prescribed a transfusion based exclusively on Hb value. Results indicate that clinical judgment and patient symptoms, not just Hb value, were used in decisions to prescribe PRBC transfusions.

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Stenotrophomonas maltophilia bacteremia and pneumonia at a tertiary-care oncology center: a review of 16 years

Abstract

Purpose

The aim of this study was to describe the clinical characteristics and antimicrobial patterns of Stenotrophomonas maltophilia bloodstream infections (BSI) and pneumonia episodes in patients with cancer.

Methods

Patients with S. maltophilia BSI or pneumonia admitted from 1 Jan. 2000 to 31 Dec. 2016 were identified at the Instituto Nacional de Cancerología (INCan), a tertiary-care oncology hospital in Mexico City.

Results

During the study period, there were 171 isolates identified. The mean age of the whole group was 46.9 ± 17.4 years; 99 (57.9%) were women. There were 95 BSI: 64 ambulatory catheter-related BSI (CRBSI), 20 nosocomial CRBSI, and 11 secondary BSI. Mortality was higher in nosocomial CRBSI (40%) vs. that in ambulatory CRBSI (7.8%) (p = 0.001). There were 76 pneumonia episodes; all were nosocomial acquired; 46 (60.5%) ventilator-associated. From all the group, nine strains (5.2%) were resistant to sulfamethoxazole/trimethoprim/(SMX/TMP). At the first month, 54 patients (31.6%) have died, 38 due to pneumonia (70%) and 16 due to BSI (30%, p < 0.001). Multivariate analysis showed that removal of central venous catheter was associated with a favorable outcome in patients with bacteremia. For patients with pneumonia, age ≥ 65 years and inappropriate antimicrobial treatment were risk factors associated with 30-day mortality.

Conclusions

S. maltophilia related with ambulatory CRBSI have a better prognosis than other sources of BSI. Older patients with pneumonia who do not receive appropriate antibiotics have higher mortality. SMX/TMP is still the antibiotic of choice.

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Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases

Abstract

Objective

The palliative treatment for cervico-thoracic spinal metastases is based on a three-dimensional conformal radiation therapy (3D-CRT). Digestive toxicities are common and cause a clinical impact frequently underestimated in patients. We performed a retrospective study of digestive side effects occurring after palliative 3D-CRT for cervico-thoracic spinal metastases.

Patients and methods

All patients receiving palliative 3D-CRT at Jean Bernard Center from January 2013 to December 2014 for spinal metastases between the 5th cervical vertebra (C5) and the 12th thoracic vertebra (T12) were eligible. Three-dimensional conformal RT was delivered by a linear accelerator (CLINAC, Varian). Premedication to prevent digestive toxicities was not used. Adverse events ("esophagitis" and "nausea and/or vomiting") were evaluated according to the NCI-CTCae (version 4).

Results

From January 2013 to December 2014, 128 patients met the study criteria. The median age was 68.6 years [31.8; 88.6]. Most patients (84.4%) received 30 Gy in 10 fractions. The median overall time of treatment was 13 days [3–33]. Forty patients (31.3%) suffered from grade ≥ 2 of "esophagitis" (35 grade 2 (27.4%) and 5 grade 3 (3.9%)). Eight patients (6.3%) suffered from grade ≥ 2 of "nausea and/or vomiting" (6 grade 2 (4.7%), 1 grade 3 (0.8%), and 1 grade 4 (0.8%)).

Conclusion

The high incidence of moderate to severe digestive toxicities after palliative 3D-CRT for cervico-thoracic spinal metastases led to consider static or dynamic intensity-modulated radiation therapy (IMRT) to reduce the dose to organ at risk (the esophagus and stomach). Dosimetric studies and implementation in the clinic should be the next steps.

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Influence of family on expected benefits of complementary and alternative medicine (CAM) in cancer patients

Abstract

Background

Cancer patients often use complementary and alternative medicine (CAM) based on recommendations from family. However, the relationship between family endorsement of CAM and the patient's expectation of its benefits has never been quantified.

Methods

Between 2010 and 2011, we conducted a cross-sectional survey study among patients with a diagnosis of cancer recruited from thoracic, breast, and gastrointestinal medical oncology clinics at a single academic cancer center. We performed multivariate linear regression analyses to evaluate the relationship between perceived family endorsement of and expected benefits from CAM, adjusting for covariates.

Results

Among the 962 participants, 303 (31.3%) reported family endorsement of CAM use. Younger patients and those who had college or higher education were more likely to report family endorsement (both p < 0.05). Patients with family support had expectation scores that were 15.9 higher than patients without family support (coefficient 15.9, 95% CI 13.5, 18.2, p < 0.001). Participants with family encouragement of CAM use were also more likely to expect CAM to cure their cancer (12 vs. 37%) and prolong their life (24 vs. 61%). These relationships remained highly significant after adjusting for covariates).

Conclusions

Family endorsement of CAM use is strongly associated with patient expectation of its clinical efficacy, including expectations for cure and improved survival. These findings underscore the importance of including family in counseling and education on CAM use in order to achieve realistic patient expectations, maximize benefits, and avoid potential medical adverse effects through herb-drug interactions or rejections of conventional care.

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An investigation into the nutritional status of patients receiving an Enhanced Recovery After Surgery (ERAS) protocol versus standard care following Oesophagectomy

Abstract

Purpose

Enhanced Recovery After Surgery (ERAS) protocols have been effectively expanded to various surgical specialities including oesophagectomy. Despite nutrition being a key component, actual nutrition outcomes and specific guidelines are lacking. This cohort comparison study aims to compare nutritional status and adherence during implementation of a standardised post-operative nutritional support protocol, as part of ERAS, compared to those who received usual care.

Methods

Two groups of patients undergoing resection of oesophageal cancer were studied. Group 1 (n = 17) underwent oesophagectomy between Oct 2014 and Nov 2016 during implementation of an ERAS protocol. Patients in group 2 (n = 16) underwent oesophagectomy between Jan 2011 and Dec 2012 prior to the implementation of ERAS. Demographic, nutritional status, dietary intake and adherence data were collected. Ordinal data was analysed using independent t tests, and categorical data using chi-square tests.

Results

There was no significant difference in nutrition status, dietary intake or length of stay following implementation of an ERAS protocol. Malnutrition remained prevalent in both groups at day 42 post surgery (n = 10, 83% usual care; and n = 9, 60% ERAS). A significant difference was demonstrated in adherence with earlier initiation of oral free fluids (p <0.008), transition to soft diet (p <0.004) and continuation of jejunostomy feeds on discharge (p <0.000) for the ERAS group.

Conclusion

A standardised post-operative nutrition protocol, within an ERAS framework, results in earlier transition to oral intake; however, malnutrition remains prevalent post surgery. Further large-scale studies are warranted to examine individualised decision-making regarding nutrition support within an ERAS protocol.

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Transfusion practices at end of life for hematopoietic stem cell transplant patients

Abstract

Purpose

Limited data exist regarding transfusion practices at end of life (EOL) for hematopoietic stem cell transplant (HSCT) patients. The purpose of this study was to examine red blood cell (RBC) and platelet transfusion practices in HSCT patients who enrolled or did not enroll in hospice.

Methods

This was a single-center, retrospective chart review in deceased HSCT patients. The primary objective was to determine the mean difference between the last transfusion and death in HSCT patients (n = 116) who enrolled or did not enroll in hospice.

Results

Sixteen (14%) and 100 (86%) patients were enrolled in hospice and not enrolled in hospice, respectively. Hospice patients observed a larger mean difference between death and last transfusion (45.9 ± 66.7 vs. 14.6 ± 48.1 days, p < 0.0001). A higher amount of platelet, but not RBC, transfusions occurred in patients not enrolled in hospice (p = 0.04). The last transfusion that occurred more than 96 h before death was observed in 12 (75%) and 22 (22%) in hospice and non-hospice patients, respectively. For HSCT patients not enrolled in hospice, 17 patients received a transfusion on the same day of death and 31 patients received the last transfusion 24 h before death.

Conclusions

Blood transfusion practices differed in HSCT patients enrolled and not enrolled in hospice. For most patients not enrolled in hospice, the last transfusion occurred 24 h before death. Future efforts should explore if limited access to blood products is a barrier to hospice enrollment for HSCT patients.

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Applying pre-participation exercise screening to breast cancer survivors: a cross-sectional study

Abstract

Purpose

Clinical guidelines recommend that breast cancer (BrCa) survivors be prescribed exercise. However, clinicians often do not prescribe exercise citing the presence of multiple health issues found among cancer survivors. No study has examined the proportion of BrCa survivors that can be prescribed a community/home-based unsupervised exercise program safely and independently, without further medical investigations or supervision.

Methods

Participants included BrCa survivors who received treatment at a university healthcare system between 2009 and 2014. We applied previously identified published guidelines for health conditions that may impede BrCa survivors from completing a community/home-based exercise program. Logistic regression models were used to quantify the magnitude of the association between demographic and clinical characteristics and the ability to perform community/home-based exercise.

Results

Among 667 BrCa survivors, 65 to 75% was classified as able to complete community/home-based exercise as recommended by the clinical guidelines. Older age, black race, treatment with chemotherapy, and treatment with radiation were associated with the potential need for further medical evaluation prior to starting exercise.

Conclusions

A large proportion of BrCa survivors can be prescribed community/home-based exercise program safely and independently, without further medical investigations or supervision. Future research will be needed to determine how to identify the subset of BrCa survivors that may benefit from medical evaluation prior to starting exercise in a manner that does not interrupt clinical oncology workflow. Approximately 35% of BrCa survivors may benefit from medical evaluation prior to starting community/home-based exercise.

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Convergent priorities and tensions: a qualitative study of the integration of complementary and alternative therapies with conventional cancer treatment

Abstract

Purpose

Demand for complementary and alternative medicine (CAM) is high among cancer patients. This, alongside growing evidence for the efficacy of some CAM therapies, is driving change within cancer centres, where evidence-based CAM therapies are increasingly provided alongside standard cancer treatments. In Australia, commitment to equitable access to healthcare is strong, and some cancer centres are now providing integrative services at no cost to the patient. This represents a significant shift in healthcare provision. This study aimed to examine health professional and patient dynamics in an integrated cancer service where CAM is provided at no cost to patients alongside standard cancer treatments. It specifically sought to understand what might drive or hinder further integration of CAM with standard treatment in the cancer context.

Methods

Qualitative interviews were undertaken with twenty key stakeholders—cancer patients, cancer nurses, and oncologists—who were delivering or receiving care in an Australian public hospital where acupuncture services are provided at no cost to patients alongside standard chemotherapy and radiation treatments.

Results

Findings point to key areas where the concerns and priorities of cancer patients, cancer nurses, and oncologists converge and diverge in ways that reflect core personal and professional interests regarding patient care needs, the evidence base for CAM efficacy and safety, and rising healthcare costs.

Conclusions

Understanding points of convergence and divergence could assist clinicians and service providers in negotiating ways forward for integrative cancer services.

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Subjective and psychological well‐being in Parkinson's Disease: A systematic review

Acta Neurologica Scandinavica, EarlyView.


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Frontal sinus schwannoma

Publication date: Available online 25 April 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J. Petersen, L. Gilain, A. Coutu, N. Saroul
IntroductionNasal sinus schwannomas are rare tumors, particularly in the frontal sinus.Case reportThe authors report the case of a woman with left frontal sinus schwannoma discovered in a context of frontal sinusitis with orbital and ocular complications. The surgical procedure consisted of endonasal tumor resection and external drainage.DiscussionThe pathogenesis of frontal sinus schwannomas remains unclear. These tumors can present with a wide range of clinical and radiological signs, making them difficult to diagnosis. Surgical resection of these tumors is also complex.



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Sarcomatoid pilomatrix carcinoma

Journal of Cutaneous Pathology, EarlyView.


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A Clinical Study of Effect of Hyperpyrexia on Otoacoustic Emissions in Children

Abstract

Various degrees of sensory neural hearing loss can be seen in the progression of some hereditary periodic fever syndromes. Otoacoustic emission testing can help to establish the inner ear involvement at an early period of a periodic fever with a risk of hearing loss (Abdul Kadir et al. in J Int Adv Otol 9(2.79):08–11, 2014). Sensorineural hearing loss is the common most complication of bacterial meningitis in childhood (Richardson in Pediatrics 102(6):1364–1368, 1998). When present from birth, or acquired in the pre-school years, hearing loss of any degree, even mild hearing loss, interferes with speech and language development. In addition to obvious communication deficits, the consequences of hearing loss in children and adults include psychosocial problems, such as frustration, irritability, anxiety, the tendency to withdraw from social interactions, and even depression (Dhar and Hall in Otoacoustic emissions: principles, procedures, and protocols, Plural Publishing, San Diego, 2011). OAE are acoustic signals emitted from cochlea to the middle ear and into the external ear where they are recorded. Evoked OAE are undetectable when deafness is above 30–35 dB Sound pressure level (Biswas in Clinical audio-vestibulometry for otologists and neurologists, Bhalani Publishing House, Mumbai, 1995). OAEs permit early detection of inner ear abnormalities associated with a wide variety of diseases and disorders, including Alport syndrome etc. With early detection, the serious consequences of hearing loss can sometimes be prevented. With proper identification and diagnosis of hearing impairment, timely and effective management for the same can be taken. Data for this study was collected from children (5–14 years) attending the Department of Otorhinolaryngology and Paediatrics Out-patient departments in P.E.S.I.M.S.R, Kuppam. Among the study population 43 (57.3%) were male and 32 (42.7%) were females showing the slight male preponderance. study was done on children with temperature > 1000 F, children with temperature were screened with OAE, and OAE was recorded in same children once fever has subsided and results were compared. This is a new study where we compared same group of children with fever and once fever has subsided. In most other studies, study group was compared to the healthy control group. In our study, children with fever having abnormal FDP values at f1were 9, they reverted back to base line once fever has subsided. This shows that there is no much damage to inner ear at lower frequencies. Almost 47 abnormal FDP values at f2 reverted back to normal. At higher frequencies (f3 and f4), there is no much change in abnormal FDPs with fever and after fever has subsided, this shows that there is more damage to inner ear at higher frequencies. This study demonstrated that hyperpyrexia causes hearing loss in children with fever probably due to cochlear involvement. We conclude that OAE can be used as a screening tool in detecting hearing loss among children because the technique is simple, reproducible, not expensive, not time consuming also effectively narrows down the children with high chances of hearing loss thereby effectively improves the chances of early diagnosis and hence children can be rehabilitated early, making a marked change in their future.

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Unexpected Response Profiles Seen in Hepatitis C Virus-Infected Patients Treated with Sofosbuvir Plus Ribavirin: Five Case Reports

Viral Immunology, Ahead of Print.


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Coexistence of glandular papilloma and sclerosing pneumocytoma in the bronchiole

Pathology International, EarlyView.


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Impact of clinical trial participation on survival in patients with castration-resistant prostate cancer: a multi-center analysis

Abstract

Background

Clinical trial (CT) participation may confer access to new, potentially active agents before their general availability. This study aimed to investigate the potential survival benefit of participation in investigational CTs of novel hormonal, chemotherapeutic, and radiopharmaceutical agents in patients with castration-resistant prostate cancer (CRPC).

Methods

This multi-center, retrospective analysis included 299 consecutive patients with newly diagnosed, non-metastatic or metastatic CRPC between September 2009 and March 2017. Of these, 65 (21.7%) patients participated in CTs pertaining to systemic treatment targeting CRPC and 234 (78.3%) patients received pre-established, standard systemic treatment outside of a CT setting. The survival advantage of CT participation regarding cancer-specific survival (CSS) was investigated.

Results

An Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at CRPC diagnosis was found in a lower proportion CT participants than in non-participants (4.6% vs. 14.9%; p = 0.033). During the median follow-up period of 16.0 months, CT participants exhibited significantly higher 2-year CSS survival rates (61.3% vs. 42.4%; p = 0.003) than did non-participants. Multivariate analysis identified prostate-specific antigen and alkaline phosphatase levels at CRPC onset, Gleason score ≥ 8, ECOG PS ≥2, less number of docetaxel cycles administered, and non-participation in CTs as independent predictors for a lower risk of CSS.

Conclusions

Patients diagnosed with CRPC who participated in CTs exhibited longer CSS durations than non-participants who received pre-established, standard systemic therapy outside of a CT setting. Our findings imply that CT participation is associated with CSS, and that CT participation should be offered to patients with CRPC whenever indicated.

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Bevacizumab biosimilars: scientific justification for extrapolation of indications

Future Oncology, Ahead of Print.


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Present role and future perspectives of interventional radiology in the treatment of painful bone lesions

Future Oncology, Ahead of Print.


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Difference in prostate cancer incidence around sixty years: effects of age and metabolic diseases

Cancer Medicine, EarlyView.


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Multicenter analysis of stereotactic radiotherapy of the resection cavity in patients with brain metastases

Cancer Medicine, EarlyView.


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Adherence to Brain Trauma Foundation Guidelines for Management of Traumatic Brain Injury Patients and its Effect on Outcomes: Systematic Review

Journal of Neurotrauma, Ahead of Print.


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Development of full sweet, umami, and bitter taste responsiveness requires Regulator of G protein Signaling-21 (RGS21)

Abstract

The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21 -- a GPCR signaling negative regulator -- should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.

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Adherence to Brain Trauma Foundation Guidelines for Management of Traumatic Brain Injury Patients and its Effect on Outcomes: Systematic Review

Journal of Neurotrauma, Ahead of Print.


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Inhibiting IL-2 signaling and the regulatory T-cell pathway using computationally designed peptides

Summary

Background Increased serum levels of soluble interleukin-2 (IL-2) receptor alpha (sIL-2Rα) are an indicator of poor prognosis in patients with B-cell non-Hodgkin lymphoma (NHL). By binding to IL-2, sIL-2Rα upregulates Foxp3 expression and induces the development of regulatory T (T_reg) cells. Methods To inhibit the binding of IL-2 to sIL-2Rα with the goal of suppressing the induction of Foxp3 and decreasing T_reg cell numbers, we developed peptides by structure-based computational design to disrupt the interaction between IL-2 and sIL-2Rα. Each peptide was screened using an enzyme-linked immunosorbent assay (ELISA), and 10 of 22 peptides showed variable capacity to inhibit IL-2/sIL-2Rα binding. Results We identified a lead candidate peptide, CMD178, which consistently reduced the expression of Foxp3 and STAT5 induced by IL-2/sIL-2Rα signaling. Furthermore, production of cytokines (IL-2/interferon gamma [IFN-γ]) and granules (perforin/granzyme B) was preserved in CD8⁺ T cells co-cultured with IL-2–stimulated CD4⁺ T cells that had been pretreated with CMD178 compared to CD8⁺ cells co-cultured with untreated IL-2–stimulated CD4⁺ T cells where it was inhibited. Conclusions We conclude that structure-based peptide design can be used to identify novel peptide inhibitors that block IL-2/sIL-2Rα signaling and inhibit T_reg cell development. We anticipate that these peptides will have therapeutic potential in B-cell NHL and other malignancies.

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Quantitative dynamic susceptibility contrast perfusion-weighted imaging-guided customized gamma knife re-irradiation of recurrent high-grade gliomas

Abstract

Introduction

Treatment of recurrent high-grade gliomas (rHGG) has always been challenging. This study aimed to explore the treatment effect of quantitative dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI)-guided gamma knife radiosurgery (GKRS) on rHGG.

Methods

Between April 2014 and July 2016, 26 consecutive patients were treated by quantitative DSC-PWI-guided GKRS as salvage treatment for rHGG. The gross tumor volume (GTV) was defined as the high perfusion area on absolute cerebral blood volume maps, with a cutoff value of 22 ml/100 g. The clinical target volume (CTV) encompassed the GTV by 3 mm. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan–Meier method. Prognostic factors were tested by the log-rank (Mantel–Cox) test.

Results

With a median follow-up of 32 months, the median PFS after GKRS was 8 months (95% CI [6, 12]); the 1- and 2-year survival rates were 30.8 and 11.5%, respectively. The median OS was 25.5 months (95% CI [18, 40]); the 1- and 2-year survival rates were 96.2 and 57.7%, respectively. Pathology grade and CTV were identified as prognostic factors for PFS. However, none of the parameters tested were independent prognostic factors for OS among these selected patients. No severe radiotoxicity was observed among all patients.

Conclusions

Quantitative DSC-PWI-guided GKRS is feasible for the treatment of rHGG and that these outcomes remain to be validated. Despite this, we think that carefully selected patients can benefit from this treatment method.

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Inventory of methane emissions from livestock in China from 1980 to 2013

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Jiashuo Yu, Shushi Peng, Jinfeng Chang, Philippe Ciais, Patrice Dumas, Xin Lin, Shilong Piao
Livestock is the largest anthropogenic methane (CH4) source at the global scale. Previous inventories of this source for China were based on the accounting of livestock populations and constant emission factors (EFs) per head. Here, we re-evaluate how livestock CH4 emissions have changed from China over the last three decades, considering increasing population, body weight and milk production per head which cause EF to change with time, and decreasing average life span (ALS) of livestock. Our results show that annual CH4 emissions by livestock have increased from 4.5 to 11.8 Tg CH4 yr⁻¹ over the period 1980–2013. The increasing trend in emissions (0.25 Tg CH4 yr⁻²) over this period is ∼12% larger than that if using constant EFs and ALS. The increasing livestock population, production per head and decreasing ALS contributed +91%, +28% and −19% to the increase in CH4 emissions from livestock, respectively. This implies that the temporal changes in EF and ALS of livestock cannot be overlooked in inventories, especially in countries like China where livestock production systems are experiencing rapid transformations.



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Homologous series of n-alkanes (C19-C35), fatty acids (C12-C32) and n-alcohols (C8-C30) in atmospheric aerosols from central Alaska: Molecular distributions, seasonality and source indices

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Suresh K.R. Boreddy, Md. Mozammel Haque, Kimitaka Kawamura, Pingqing Fu, Yongwon Kim
To better understand the molecular distributions, seasonality and source indices of organic aerosols in central Alaska, we measured homologous series of n-alkanes (C19-C35), fatty acids (C12-C32) and n-alcohols (C8-C30) in total suspended aerosols collected during June 2008 to 2009 using a gas chromatography/mass spectrometry (GC-MS). The whole sampling period was divided as warm (early May to late September; summer) and cold (late September to early May; winter) periods. Molecular distribution was characterized in both periods by the predominance of C25 for n-alkanes and C24:0 for fatty acids. However, we noticed a difference in molecular distribution of n-alcohols between warm and cold periods, which was characterized by the predominance of C22 in warm season while C26 in cold period. Except for fatty acids, n-alkanes and n-alcohols showed higher concentrations in warm period than in cold period. We found significantly higher ratios of C18:1/C18:0 in warm period than those in cold period, suggesting the fresh biogenic and aged anthropogenic aerosols in warm and cold periods, respectively. This inference was consistent with significantly higher ratios of WSOC/OC, a proxy for photochemical aging, in cold period. Based on the carbon preference index (CPI), average chain length (ACL), low-to-high molecular weight (LMW/HMW) ratios, wax n-alkanes (%WNA) and estimated fossil fuel concentrations, we demonstrate that higher plant waxes, biomass burning from wildfires are two important sources in warm period while combustion derived anthropogenic emissions are major sources in cold period in central Alaska. This finding was further supported by higher ratios of nss-K⁺/elemental carbon (EC) and methanesulfonate (MSA⁻)/EC ratios in warm period.



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A cool-temperate young larch plantation as a net methane source - A 4-year continuous hyperbolic relaxed eddy accumulation and chamber measurements

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Masahito Ueyama, Kota Yoshikawa, Kentaro Takagi
Upland forests are thought to be methane (CH4) sinks due to oxidation by methanotrophs in aerobic soils. However, CH4 budget for upland forests are not well quantified at the ecosystem scale, when possible CH4 sources, such as small wet areas, exists in the ecosystem. Here, we quantified CH4 fluxes in a cool-temperate larch plantation based on four-year continuous measurements using the hyperbolic relaxed eddy accumulation (HREA) method and dynamic closed chambers with a laser-based analyzer. After filling data gaps for half-hourly data using machine-learning-based regressions, we found that the forest acted as a net CH4 source at the canopy scale: 30 ± 11 mg CH4 m⁻² yr⁻¹ in 2014, 56 ± 8 mg CH4 m⁻² yr⁻¹ in 2015, 154 ± 5 mg CH4 m⁻² yr⁻¹ in 2016, and 132 ± 6 mg CH4 m⁻² yr⁻¹ in 2017. Hotspot emissions from the edge of the pond could strongly contribute to the canopy-scale emissions. The magnitude of the hotspot emissions was 10–100 times greater than the order of the canopy-scale and chamber-based CH4 fluxes at the dry soils. The high temperatures with wet conditions stimulated the hotspot emissions, and thus induced canopy-scale CH4 emissions in the summer. Understanding and modeling the dynamics of hotspot emissions are important for quantifying CH4 budgets of upland forests. Micrometeorological measurements at various forests are required for revisiting CH4 budget of upland forests.



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Real world vehicle fleet emission factors: Seasonal and diurnal variations in traffic related air pollutants

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Jonathan M. Wang, Cheol-Heon Jeong, Naomi Zimmerman, Robert M. Healy, Greg J. Evans
Temporal variations of vehicle emissions are affected by various compounding factors in the real world. The focus of this study is to determine the effects of ambient conditions and post-tailpipe changes on traffic emissions measured in the near-road region. Emission factors allowed for the isolation of the traffic signal and accounted for effects of local meteorology and dilution. Five month-long measurement campaigns were conducted at an urban near-road site that exhibited a broad range of ambient conditions with temperatures ranging between −18 and +30 °C. Particle number emission factors were 2.0× higher in the winter relative to the summer, which was attributed to changes in particles post-tailpipe. Conversely, toluene emissions were 2.5× higher in the summer relative to the winter, attributed to changes in fuel composition. Diurnal trends of emission factors showed substantial increases in emissions during the morning rush hour for black carbon (1.9×), particle number (2.4×), and particle-bound polycyclic aromatic hydrocarbons (3.0×), affected by fleet make-up. In contrast, particle number emission factors were highest midday with mean values 3.7× higher than at night. This midday increase was attributed to particle formation or growth from local traffic emissions and showed different wind direction dependence than regional events.



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Small-scale variations in ozone concentration in low mountains

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Isao Kanda, Shinji Wakamatsu
In a relatively low mountain area adjacent to Matsuyama city in Japan, ozone concentration variations were studied at spatial scales of O(10)∼O(103) m. Walking mobile measurements were complemented by vertical profiling, wind measurements, and passive sampling. The broad-scale distribution at O(102)∼O(103) m was found to depend on time of day, atmospheric stability, and geography in ways consistent with previous studies. Well-defined areas of low ozone concentrations O(10) m in width were found at several locations. No distinctive features of these locations were immediately discernible, but detailed examination of the temporal variations coupled with the wind field suggested that the distribution of the low-ozone areas was determined by subtle differences in the terrain topography.



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An international survey on hybrid imaging: do technology advances preempt our training and education efforts?

Abstract

Background

Hybrid PET/CT and PET/MRI are increasingly important technologies in the evaluation of malignancy and require cooperation between radiologists and specialists in molecular imaging. The aim of our study was to probe the mindsets of radiological and nuclear medicine professionals in regard to current hybrid imaging practice and to assess relevant training aspirations and perceived shortfalls, particularly amongst young professionals. In this context, we initiated an international survey on "Hybrid Imaging Training".

Methods

An online survey was prepared on-line and launched on October-2, 2016. It was composed of 17 multiple-choice and open questions regarding the professional background, a perspective on hybrid imaging training efforts and lessons to be learned from disparate craft groups. The survey ran for 2 weeks. We report total responses per category and individual free-text responses.

Results

In total, 248 responses were collected with a mean age of all responders of (41 ± 11) y. Overall, 36% were within the target age range of (20–35) y. Across all responders, the majority (72%) commented on there being too few hybrid imaging experts in their country, whereas only 1% said that there were too many. Three quarters of the responders were in favour of a curriculum allowing sub-specialisation in hybrid imaging. With respect to reporting of hybrid imaging, confidence increased with age. The average rating across all responders on the level of cooperation among the two specialties suggested a low overall level of satisfaction. However, the survey feedback indicated the local (on-site) cooperation being somewhat better than the perceived cooperation between the relevant associations on a European level.

Conclusion

We consider these results to represent an appropriate cross-section of professional opinions of imaging experts across different demographic and hierarchical levels. Collectively they provide evidence supporting a need to address current shortfalls in developing hybrid imaging expertise through national educational plans, and, thus, contribute to helping improve patient care.

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Amphotericin B suppresses M2 phenotypes and B7-H1 expression in macrophages to prevent Raji cell proliferation

Abstract

Background

Macrophages in the tumor microenvironment play a critical role in tumorigenesis and anti-cancer drug resistance. Burkitt's lymphoma (BL) is a B-cell non-Hodgkin's lymphoma with dense macrophage infiltration. However, the role for macrophages in BL remains largely unknown.

Methods

B7-H1, a transmembrane glycoprotein in the B7 family, suppresses T cell activation and proliferation and induces the apoptosis of activated T cells. The expression of B7-H1 in BL clinical tissues was determined by streptavidin-peroxidase immunohistochemistry. The mutual regulation between macrophages and BL Raji cells was investigated in a co-culture system. The cell proliferation and cell cycle distribution of Raji cells were determined using BrdU staining coupled with flow cytometry. CD163, CD204 and B7-H1 expression was assessed by flow cytometry and Western blot. Cell invasion was analyzed by Transwell assay. The expression of cytokines was detected by quantitative RT-PCR. Immunofluorescence and allogeneic T-cell proliferation assays were used to compare the expression of B7-H1, p-STAT6, or p-STAT3 and CD3+ T cell proliferation treated with or without amphotericin B.

Results

B7-H1 was highly expressed in tumor infiltration macrophages in most clinical BL tissues. In vitro, Raji cells synthesized IL-4, IL-6, IL-10 and IL-13 to induce CD163, CD204 and B7-H1 expression in co-cultured macrophages, which in turn promoted Raji cell proliferation and invasion. Interestingly, antifungal agent amphotericin B not only inhibited STAT6 phosphorylation to suppress the M2 polarization of macrophages, but also promoted CD3+ T cell proliferation by regulating B7-H1 protein expression in macrophages.

Conclusion

Amphotericin B might represent a novel immunotherapeutic approach to treat patients with BL.

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A high-content screening of anti-cancer compounds suggests the multiple tyrosine kinase inhibitor ponatinib for repurposing in neuroblastoma therapy

Novel druggable targets have been discovered in neuroblastoma (NB), paving the way for more effective treatments. However, children with high-risk NB still show high mortality rates prompting for a search of novel therapeutic options. Here, we aimed at repurposing FDA-approved drugs for NB treatment by performing a high-content screening of a 349 anti-cancer compounds library. In the primary screening we employed three NB cell lines, grown as 3D multicellular spheroids, which were treated with 10 μM of the library compounds for 72 hours. The viability of 3D spheroids was evaluated using a high-content imaging approach, resulting in a primary hit list of 193 compounds. We selected 60 FDA-approved molecules and prioritized drugs with multi-target activity, discarding those already in use for NB treatment or enrolled in NB clinical trials. Hence, 20 drugs were further tested for their efficacy in inhibiting NB cell viability, both in 2D and 3D models. Dose-response curves were then supplemented with the data on side-effects, therapeutic index and molecular targets, suggesting two multiple tyrosine kinase inhibitors, ponatinib and axitinib, as promising candidates for repositioning in NB. Indeed, both drugs showed induction of cell cycle block and apoptosis, as well as inhibition of colony formation. However, only ponatinib consistently affected migration and inhibited invasion of NB cells. Finally, ponatinib also proved effective inhibition of tumor growth in orthotopic NB mice, providing the rationale for its repurposing in NB therapy.

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Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla®, T-DM1), an antibody-drug conjugate that is comprised of trastuzumab covalently linked to the anti-mitotic agent DM1 through a stable linker, was designed to selectively deliver DM1 to HER2-overexpressing tumor cells. T-DM1 is approved for the treatment of patients with HER2-positive metastatic breast cancer following progression on trastuzumab and a taxane. Despite the improvement in clinical outcome, many patients who initially respond to T-DM1 treatment eventually develop progressive disease. The mechanisms that contribute to T-DM1 resistance are not fully understood. To this end, we developed T-DM1-resistant in vitro models to examine the mechanisms of acquired T-DM1 resistance. We demonstrate that decreased HER2 and up-regulation of MDR1 contribute to T-DM1 resistance in KPL-4 T-DM1 resistant cells. In contrast, both loss of SLC46A3 and PTEN deficiency play a role in conferring resistance in BT-474M1 T-DM1 resistant cells. Our data suggest that these two cell lines acquire resistance through distinct mechanisms. Furthermore, we show that the KPL-4 T-DM1 resistance can be overcome by treatment with an inhibitor of MDR1, whereas a PI3K inhibitor can rescue PTEN loss-induced resistance in T-DM1-resistant BT-474M1 cells. Our results provide a rationale for developing therapeutic strategies to enhance T-DM1 clinical efficacy by combining T-DM1 and other inhibitors that target signaling transduction or resistance pathways.

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Molecular Profile of Advanced Thyroid Carcinomas by Next-Generation Sequencing: Characterizing tumors beyond diagnosis for targeted therapy

Next generation sequencing (NGS) for molecular diagnostics allows simultaneous testing of activating oncogenes and tumor suppressor mutations in multiple signal pathways. Extended mutational profiling of advanced thyroid cancers may enhance considerations for targeted therapies. We analyzed clinically derived molecular profiling of 216 patients with advanced thyroid carcinoma using NGS (Ion Torrent Personal Genome Machine) from 4/2012-2/2014. We examined substitutions and small indels in 46/50 cancer-related genes using Ampliseq Cancer Hotspot panel in respect to tumor diagnosis and clinical correlations. Mutations were common in advanced thyroid carcinomas 154 (71%) predominately in targetable MAPK pathway (146/216, 68%), and several PI3K/AKT pathway (8, 4%; 6 as co-mutations). BRAF V600E mutation associated with papillary (94/139, 68%), poorly differentiated (4/39, 10%) and anaplastic (3/12, 25%) carcinomas. NRAS mutations occurred in follicular (5/12, 40%) and poorly differentiated thyroid carcinoma (12/39, 31%). Tumor suppressor mutations (16, 7%) occurred predominantly in TP53 in Hurthle cell (2/5, 40%, the only mutation), in anaplastic (3/12, 25%), and poorly differentiated thyroid carcinoma (4/39, 10%) some co-mutations and in papillary thyroid carcinoma (5/139, 4%) always a co-mutation. Kaplan-Meier analysis showed patients with poorly differentiated thyroid carcinoma containing activating mutations who received targeted therapeutics showed improved survival compared to similarly treated patients without mutations in targetable pathways (p=0.02). In conclusion, MAPK pathway is the predominant target for therapy in advance thyroid carcinomas; adding NGS enables the identification of co-mutations associated with resistance (PI3K/AKT). Within poorly differentiated thyroid carcinoma, the molecular profile may hold prognostic value in the era of targeted therapy.

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Improving the in vivo efficacy of an anti-Tac (CD25) immunotoxin by Pseudomonas exotoxin A domain II engineering

Tac (CD25) is expressed on multiple hematological malignancies and is a target for cancer therapies. LMB-2 is an extremely active anti-Tac recombinant immunotoxin composed of an Fv that binds to Tac and a 38kDa fragment of Pseudomonas exotoxin A (PE38). While LMB-2 has shown high cytotoxicity towards Tac-expressing cancer cells in clinical trials, its efficacy was hampered by the formation of anti-drug antibodies against the immunogenic bacterial toxin and by dose-limiting off-target toxicity. To reduce toxin immunogenicity and non-specific toxicity, we introduced six point mutations into domain III that were previously shown to reduce T cell immunogenicity and deleted domain II from the toxin, leaving only the 11aa furin cleavage site which is required for cytotoxic activity. While this strategy has been successfully implemented for mesothelin and CD22 targeting immunotoxins, we found that removal of domain II significantly lowered the cytotoxic activity of αTac immunotoxins. To restore cytotoxic activity in the absence of PE domain II, we implemented a combined rational design and screening approach to isolate highly active domain II deleted toxin variants. The domain II deleted variant with the highest activity contained an engineered disulfide-bridged furin cleavage site designed to mimic its native conformation within domain II. We found that this approach restored five-fold of the cytotoxic activity and dramatically improved the maximum tolerated dose. Both of these improvements led to significantly increased anti-tumor efficacy in vivo. We conclude that the next generation anti-Tac immunotoxin is an improved candidate for targeting Tac expressing malignancies.

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ASTX660, a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP, potently induces TNF-{alpha} dependent apoptosis in cancer cell lines and inhibits tumor growth

Due to their roles in the evasion of apoptosis, Inhibitor of Apoptosis Proteins (IAPs) are considered attractive targets for anti-cancer therapy. Antagonists of these proteins have the potential to switch pro-survival signaling pathways in cancer cells towards cell death. Various SMAC-peptidomimetics with inherent cIAP selectivity have been tested clinically and demonstrated minimal single agent efficacy. ASTX660 is a potent, non-peptidomimetic, antagonist of cIAP1/2 and XIAP, discovered using fragment-based drug design. The antagonism of XIAP and cIAP1 by ASTX660 was demonstrated on purified proteins, cells and in vivo in xenograft models. The compound binds to the isolated BIR3 domains of both XIAP and cIAP1 with nanomolar potencies. In cells and xenograft tissue direct antagonism of XIAP was demonstrated by measuring its displacement from caspase-9 or SMAC. Compound-induced proteasomal degradation of cIAP1 and 2, resulting in downstream effects of NIK stabilization and activation of non-canonical NF-B signaling, demonstrated cIAP1/2 antagonism. Treatment with ASTX660 led to TNF-α-dependent induction of apoptosis in various cancer cell lines in vitro, while dosing in mice bearing breast and melanoma tumor xenografts inhibited tumor growth. ASTX660 is currently being tested in a phase 1-2 clinical trial (NCT02503423) and we propose that its antagonism of cIAP1/2 and XIAP may offer improved efficacy over first-generation antagonists that are more cIAP1/2 selective.

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Selective targeting and eradication of LGR5+ CSCs using RSPO conjugated doxorubicin liposomes

Cancer stem cells (CSCs) that may account for only a small fraction of tumor mass were found to play crucial roles during tumor initiating, progression and metastasis. However, they are usually difficult to be treated and notoriously resilient to drug eradication. In this study we aimed at the Wnt signaling characteristic of cancer stem cells and designed a liposomal drug delivery system to target CSCs. Liposomes decorated with RSPO1 on the surface were constructed for specific interactions with the Wnt pathway co-receptor LGR5. Doxorubicin carried by the RSPO1-liposomes was more effective at lower concentrations than the same drug loaded in PEG-liposomes. More importantly, we showed using a Patient Derived Xerograft (PDX) tumor model where LGR5+ CSCs co-existed with LGR5- cells, the RSPO1-liposomes were able to access more CSC cells and deliver the drug specifically and efficiently. Such a focused effect in eradicating LGR5+ cells led to massive tumor tissue necrosis and growth inhibition even when only a fraction of the conventional drug dose was used. These data clearly demonstrated the advantages of CSC targeted drug delivery and would support the development of such approaches as a new cancer treatment strategy.

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Tumor-independent host secretomes induced by angiogenesis and immune-checkpoint inhibitors

The levels of various circulating blood proteins can change in response to cancer therapy. Monitoring therapy-induced secretomes (TIS) may have use as biomarkers for establishing optimal biological effect (such as dosing) or identifying sources of toxicity and drug resistance. While TIS can derive from tumor cells directly, non-tumor 'host' treatment responses can also impact systemic secretory programs. For targeted inhibitors of the tumor microenvironment, including antiangiogenic and immune-checkpoint therapies, host TIS could explain unexpected collateral 'side-effects' of treatment. Here we describe a comparative transcriptomic and proteomic analysis of host TIS in tissues and plasma from cancer-free mice treated with antibody and receptor tyrosine kinase inhibitors (RTKIs) of the VEGF, cMet/ALK, and PD-1 pathways. We found that all cancer therapies elicit TIS independent of tumor growth, with systemic secretory gene change intensity higher in RTKIs compared to antibodies. Our results show that host TIS signatures differ between drug target, drug class, and dose. Notably, protein and gene host TIS signatures were not always predictive for each other, suggesting limitations to transcriptomic-only approaches to clinical biomarker development for circulating proteins. Together, these are the first studies to assess and compare 'off-target' host secretory effects of VEGF and PD-1 pathway inhibition that occur independent of tumor stage or tumor response to therapy. Testing treatment impact on normal tissues to establish host-mediated TIS signatures (or 'therasomes') may be important for identifying disease agnostic biomarkers to predict benefits (or limitations) of drug combinatory approaches.

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Relationship between motion sickness susceptibility and vestibulo-ocular reflex gain and phase.

Related Articles

Relationship between motion sickness susceptibility and vestibulo-ocular reflex gain and phase.

J Vestib Res. 2018 Apr 18;:

Authors: Clément G, Reschke MF

Abstract
BACKGROUND: It has been proposed that individual susceptibility to motion sickness is related to the vestibulo-ocular reflex (VOR) through the activation of the velocity storage mechanism.
OBJECTIVE: We investigated whether motion sickness level was related to the gain and phase of the VOR.
METHODS: VOR gain and phase were measured in 214 subjects while they rotated in yaw at 0.01 Hz, 0.02 Hz, 0.04 Hz, 0.08 Hz, and 0.16 Hz in darkness, and results were compared to the severity of symptoms the subjects experienced during subsequent tests to provoke motion sickness. These tests included cross-coupled angular accelerations, sudden stops in light or in dark, off-vertical axis rotation, and parabolic flight. The subjects were grouped according to the motion sickness level reached during these tests (none, low, medium, or high).
RESULTS: No correlation was found between the horizontal VOR gain and motion sickness level. However, for the subjects with high motion sickness level, the VOR phase lead was significantly lower during rotation at frequencies ranging from 0.04 Hz to 0.16 Hz (i.e. the VOR time constant was longer) than the other motion sickness groups.
CONCLUSION: These results support the theory that the longer the time constant for velocity storage, the more severe the motion sickness.

PMID: 29689763 [PubMed - as supplied by publisher]

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Seroimmunity to Hepatitis B Virus in Children With Inflammatory Bowel Disease: Effects of Booster Vaccination

No abstract available

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Safety of Appetite Manipulation in Children with Feeding Disorders Admitted to an Inpatient Feeding Program

Objective: Appetite manipulation can be effective in weaning children off gastrostomy tube feeding dependence but can cause dehydration, hypoglycaemia, and ketone body production, which is anorexigenic. As the safety of this approach has not been described, our aim was to describe adverse events observed when weaning children from G-tube dependence using our appetite manipulation protocol. Methods: This was a retrospective study of prospectively collected data of patients who completed our inpatient tube-weaning protocol. Daily safety parameters included twice-daily urine specific gravities and urine ketones and fasting capillary blood glucose. Graded clinical interventions to manage adverse events were collected. Results: A total of 143 children with a mean age of 4.8 ± 2.4 years were seen in the inpatient feeding program of which 74 (51.7%) were male. The children were hospitalized 10.1 ± 2.5 days with the vast majority being discharged between days 11 and 14. Overall, 78.2% of patients experienced at least 1 adverse event: urine specific gravity >1.020 was seen in 60.5%, ketonuria in 48.9%, and hypoglycemia (≤60 mg/dL) in 13.4%. Only 2 children had blood glucose levels

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Induced Pluripotent Stem Cell-Derived Hepatocytes and Precision Medicine in Human Liver Disease

Liver-like human cells can be generated from human skin by converting fibroblasts to "induced pluripotent stem cells" (iPSCs), then differentiating the iPSCs into "induced hepatocytes". Although still primarily used as a research tool, emerging applications involving iPSC-derived induced hepatocytes have exciting and provocative clinical and translational potential. This review provides a brief summary of the current status of this field and obstacles that must be overcome before this novel tool will enable precision medicine-based approaches to human liver disease.

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Clear Liquid Versus Low-fibre Diet in Bowel Cleansing for Colonoscopy in Children: A Randomized Trial

Objectives: In light of a paucity of data on the role of diet in colonoscopy preparation in paediatric population, the present study was designed to compare the effectiveness of clear liquid and low-fibre diets for breakfast and lunch on the day preceding colonoscopy in children. Methods: This prospective, randomised trial was conducted at the Department of Paediatric Gastroenterology and Nutrition in Warsaw, Poland. Eligible patients, referred for colonoscopies, were 6 to 18 years old. Patients were randomly divided into 2 groups: the first received a clear liquid diet and the second a low-fibre diet on the day before colonoscopy. In the afternoon, all participants were asked to drink polyethylene glycol with electrolytes at a dose of 66 mL/kg to a maximum of 4 L. The effectiveness of bowel cleansing was measured using the Boston Bowel Preparation Scale (BBPS). The preparation tolerance was assessed by parents and children using a visual analogue scale. Adverse effects were reported. Results: In total, 184 patients were enrolled. Of those, 96 received the clear liquid diet and 88—the low-fibre diet. The mean age of both groups was 15 years. There were no differences between the 2 study groups in age, weight, and sex, as well as in total BBPS score (BBPS ≥ 5 96.6% vs 95.1%, P = 0.5). The frequency of adverse effects was similar in both groups; nausea was the most common (P = 0.8). Conclusions: Clear liquid and low-fibre diets administered to children the day before colonoscopy demonstrated similar bowel cleansing effectiveness.

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The 2017 Shwachman Award

No abstract available

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Randomized Controlled Clinical Trial on Value of Domperidone in Functional Abdominal Pain in Children

Objectives: The aim of the study was to evaluate the therapeutic effect of domperidone on children with abdominal pain predominant functional gastrointestinal disorders (AP-FGIDs). Methods: One hundred children (aged 5–12 years) fulfilling Rome III criteria for AP-FGIDs were randomized into 8 weeks of domperidone or placebo treatment. Primary outcomes defined were cure and patient-reported general improvement. Secondary outcomes were reduction in the severity of abdominal pain and increase in gastric motility. Patients were followed up for 6 months. Results: Eighty-nine (42 in placebo group, 47 in domperidone group) completed the trial at 8 weeks. Seventy-nine completed the 6-month follow-up. When primary outcomes were assessed at 8 weeks, 37 (74%) in the domperidone group and 25 (50%) in the placebo group showed patient-reported general improvement (P = 0.013), whereas no significant difference was observed in cure (22 [44%] vs 14 [28%] P = 0.09). At 6-month follow-up 30 (60%) in the domperidone group and 19 (38%) in the placebo group reported cure (P = 0.028), whereas 44 (88%) in the domperidone group and 33 (66%) in the placebo group showed patient-reported general improvement (P = 0.009). When assessing secondary outcomes at 8 weeks, the domperidone group reported significant reduction in the severity of abdominal pain (54.1% vs 24.7%, P  = 0.008) and an increase in the antral motility index (27.5% vs 7.2%, P = 0.029). None of the patients reported intervention-related adverse effects. Conclusions: Domperidone may be a safe and effective therapeutic modality to achieve a lasting remission of symptoms in children with AP-FGIDs.

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Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial

Objective: A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. Methods: In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. Results: A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI −0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (−3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. Conclusions: All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

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Family Health-related Quality of Life in Pediatric Cyclic Vomiting Syndrome

Objective: The aim of the study was to evaluate the relationship of disease characteristics and child anxiety symptoms to family health-related quality of life (FHRQoL) in youth with cyclic vomiting syndrome (CVS). Methods: Forty-two parents of youth ages 8 to 18 years diagnosed with CVS completed the Family Impact Module of the PedsQL, a measure of the impact of the child's illness on the family. We evaluated the relationship of disease characteristics and child and parent proxy reports of anxiety symptoms on the Screen for Childhood Anxiety and Related Emotional Disorders to FHRQoL. Results: Parent report of child anxiety symptoms and missed school days (mean = 11.93, standard deviation = 14.62) were the strongest predictors of FHRQoL (r2 = 0.33, df = 1.39, F = 8.51, P = 0.006). Other disease characteristics, including frequency, duration, chronicity of CVS episodes, and delay in initial CVS diagnosis were not significantly associated with the FHRQoL total score. Child anxiety symptoms by either parent and/or child report were associated with subscales of the FHRQoL, including family physical functioning, family communication, and family daily activities. Conclusions: HRQoL for the families assessed in this study was associated with anxiety symptoms to a greater extent than disease characteristics, indexing the importance of a biopsychosocial approach to CVS management. Screening for anxiety symptoms and support for school absences due to illness are indicated to help lessen the impact of CVS on the family as a whole.

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Esophageal Squamous Cell Papillomatosis Arising in Focal Dermal Hypoplasia in a 3-Year-Old Girl

No abstract available

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Trends of Magnet Ingestion in Children, an Ironic Attraction

Background and Objectives: Ingestion of rare earth magnets is a serious ongoing hazard for pediatric patients. Our study aims to investigate whether 2012 Consumer Product Safety Commission (CPSC) policy action, in coordination with efforts from consumer and physician advocacy groups, decreased the incidence of magnet ingestions in children in the United States since 2012. Methods: Data from the National Electronic Injury Surveillance System (NEISS) was used to evaluate trends in emergency department (ED) encounters with pediatric patients (

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Should Giant Cell Hepatitis With Autoimmune Haemolythic Anaemia Be Considered a Paediatric Autoimmune Liver Disease?

No abstract available

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Choice of Endoscopic Procedure in Children With Clinically Suspected Gastrointestinal Graft-versus-host Disease

Objectives: Gastrointestinal graft-versus-host disease (GI-GVHD) is a potentially life-threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI-GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. Optimal extent of endoscopy in children is, however, presently unknown. Therefore, we aimed to evaluate whether biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI-GVHD and relevant differential diagnoses. Methods: Retrospective multicenter study based on histopathological re-evaluation of biopsies and hospital record data, collected from children with suspected GI-GVHD. Results: Forty-four children with 51 endoscopic occasions (81 procedures) were included. Thirty-nine of 51 (76.5%) were diagnosed as GI-GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity, that is, simultaneous detection of a differential diagnosis and GI-GVHD, was observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and esophagogastroduodenal areas. Sensitivity for detection of GI-GVHD in biopsies collected from rectosigmoid-ileocolonic-, rectosigmoid-, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter 2 were merged. The difference, nondetected GI-GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (P = 0.03). Conclusions: Biopsies collected from the rectosigmoid area solely were not optimal for detection of pediatric GI-GVHD. When biopsy sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity for GI-GVHD was, however, equally high as for ileocolonoscopy or full upper and lower endoscopy.

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Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys With Nonalcoholic Fatty Liver Disease

Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. Methods: We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with P value 5% were considered potentially significant. Results: Evaluated subjects had a median age of 12.0 years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH, and definite NASH were 23%, 53%, and 22%, respectively. The GWAS identified 10 SNPs that were associated with BMI z score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). Conclusions: This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.

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High Incidence of Proteinuria in Children With Chronic Intestinal Failure Under Long-term Parenteral Nutrition

Long-term home parenteral nutrition (LTPN) in children with chronic intestinal failure (CIF) is associated with renal complications such as fluid and electrolyte imbalances, nephrocalcinosis, nephrolithiasis, and chronic kidney disease (CKD). The etiology of CIF-associated nephropathy is multifactorial. The aim of this study was to evaluate renal involvement under LTPN. In this study, 50 patients with CIF, median age 4.2 years (1.4–9.3; 23 girls) were included. Kidney involvement was a frequent finding in this study. CKD was present in 30% of patients without correlation with LTPN duration. Glomerular proteinuria was found in the majority of patients (76%), an important long-term risk factor for the progression of CKD. Increased urinary α-1 microglobulin was significantly associated with duration (years) of LTPN and was increased in patients with CKD.

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A sustainable model for cochlear implantation in the developing world: perspectives from the Indian subcontinent

Purpose of review The overall prevalence of deafness in India is 0.2%, but the prevalence in the southern state of Tamil Nadu is much higher (around 0.6%) because of consanguinity. Especially in India, establishing cochlear implantation as a treatment modality for hearing loss has been a daunting task, but in the last decade, the cochlear implantation program has emerged as an unqualified success in many states, with over 20 000 cochlear implantations done till date. Several states are sponsoring free implants to children under the age of 6 years and below poverty line. Recent findings Nearly 3000 cochlear implantations have been performed in Tamil Nadu under the Chief Minister's Comprehensive Health Insurance Scheme, with the goal to have a 'deafness free Tamil Nadu' by 2025. This scheme covers nearly 40 million people in rural areas. Valuable lessons have been learnt from this social experiment. One of the cornerstones of this scheme is the method to deliver habilitation via satellite centers in rural areas at the doorstep of the patient. The outcomes in peripheral centers were found to be statistically similar to those in the main center and correlated well with duration of habilitation. Summary Opening up satellite centers for habilitation across the state of Tamil Nadu has greatly helped to improve the attendance and outcomes. The Indian model has been hugely successful and has helped start similar cochlear implantation programs in neighboring countries such as Nepal, Sri Lanka and Bangladesh. Correspondence to Prof. Mohan Kameswaran, Department of Neurotology and Auditory Implants, Madras ENT Research Foundation, No. 1, First Cross Street, Off. Second Main Road, Raja Annamalai Puram, Chennai 600028, Tamil Nadu, India. Tel: +91 44 24311411x412x413x414x415; fax: +91 4424311416; e-mail: merfmk30@yahoo.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition, Published online: 26 April 2018; doi:10.1038/s41416-018-0072-3

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

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Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma

Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma

Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma, Published online: 26 April 2018; doi:10.1038/s41416-018-0076-z

Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma

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Cutaneous neurofibromas in the genomics era: current understanding and open questions

Cutaneous neurofibromas in the genomics era: current understanding and open questions

Cutaneous neurofibromas in the genomics era: current understanding and open questions, Published online: 26 April 2018; doi:10.1038/s41416-018-0073-2

Cutaneous neurofibromas in the genomics era: current understanding and open questions

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Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers, Published online: 26 April 2018; doi:10.1038/s41416-018-0068-z

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

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Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer, Published online: 26 April 2018; doi:10.1038/s41416-018-0078-x

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

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Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients, Published online: 26 April 2018; doi:10.1038/s41416-018-0074-1

Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients

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Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer, Published online: 26 April 2018; doi:10.1038/s41416-018-0085-y

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

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A sustainable model for cochlear implantation in the developing world: perspectives from the Indian subcontinent

Purpose of review The overall prevalence of deafness in India is 0.2%, but the prevalence in the southern state of Tamil Nadu is much higher (around 0.6%) because of consanguinity. Especially in India, establishing cochlear implantation as a treatment modality for hearing loss has been a daunting task, but in the last decade, the cochlear implantation program has emerged as an unqualified success in many states, with over 20 000 cochlear implantations done till date. Several states are sponsoring free implants to children under the age of 6 years and below poverty line. Recent findings Nearly 3000 cochlear implantations have been performed in Tamil Nadu under the Chief Minister's Comprehensive Health Insurance Scheme, with the goal to have a 'deafness free Tamil Nadu' by 2025. This scheme covers nearly 40 million people in rural areas. Valuable lessons have been learnt from this social experiment. One of the cornerstones of this scheme is the method to deliver habilitation via satellite centers in rural areas at the doorstep of the patient. The outcomes in peripheral centers were found to be statistically similar to those in the main center and correlated well with duration of habilitation. Summary Opening up satellite centers for habilitation across the state of Tamil Nadu has greatly helped to improve the attendance and outcomes. The Indian model has been hugely successful and has helped start similar cochlear implantation programs in neighboring countries such as Nepal, Sri Lanka and Bangladesh. Correspondence to Prof. Mohan Kameswaran, Department of Neurotology and Auditory Implants, Madras ENT Research Foundation, No. 1, First Cross Street, Off. Second Main Road, Raja Annamalai Puram, Chennai 600028, Tamil Nadu, India. Tel: +91 44 24311411x412x413x414x415; fax: +91 4424311416; e-mail: merfmk30@yahoo.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling

J reconstr Microsurg
DOI: 10.1055/s-0038-1642023

Objective This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling. Methods Chronic nerve compression was created in streptozotocin (STZ)-induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed. Results Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions. Conclusion Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN.
[...]

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

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