OtoRhinoLaryngology News: 10/19/17

Πέμπτη 19 Οκτωβρίου 2017

Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric glial cell-derived nerve growth factor

Abstract

Background

Altered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic hypersensitivity via peripheral up-regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC-derived NGF is still unknown.

Methods

CRL-2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co-expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL-2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined.

Key Results

Transcriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB-treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB-treated rats. Meanwhile, a 2.1-fold increase in co-expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition.

Conclusions & Inferences

Butyrate-EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS-like animal model.

Our study illustrated that butyrate promoted the secretion of NGF from enteric glial cells (EGCs) and contributed to visceral hypersensitivity in rats. The results clarified the potential unignorable source of NGF from EGC and highlighted the important role of EGC in pathogenesis of irritable bowel syndrome (IBS).

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Association of imbalance of effector T cells and regulatory cells with the severity of asthma and allergic rhinitis in children

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High adherence to subcutaneous immunotherapy in a real-life study from a large tertiary medical center

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Hereditary angioneurotic edema … a disease has been described

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Interleukin 31 and skin diseases: A systematic review

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Management of adverse reactions to biologic agents

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Evaluation of beclomethasone dipropionate (80 and 160 micrograms/day) delivered via a breath-actuated inhaler for persistent asthma

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Indicators of poorly controlled asthma and health-related quality of life among school-age children in the United States

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Health-related quality of life in Danish children with hereditary angioedema

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Health-related quality of life in relation to disease activity in adults with hereditary angioedema in Sweden

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Efficacy of recombinant human C1 esterase inhibitor for the treatment of severe hereditary angioedema attacks

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Recombinant human C1 esterase inhibitor for acute hereditary angioedema attacks with upper airway involvement

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The role of intravenous access during oral food challenges in food protein‐induced enterocolitis syndrome

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For the Patient

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Use of Probiotics and Oral Health

Abstract

Purpose of Review

The purpose of this study is to critically assess recent studies concerning the use of probiotics to control periodontal diseases, dental caries and halitosis (oral malodour).

Recent Findings

Clinical studies have shown that probiotics when allied to conventional periodontal treatment can ameliorate microbial dysbiosis and produce significant improvement in clinical indicators of disease. However, this effect is often not maintained by the host after the end of probiotic use. Current probiotics also show limited effects in treating caries and halitosis. Novel approaches based up on replacement therapy and using highly abundant health-associated oral species, including nitrate-reducing bacteria, have been proposed to improve persistence of probiotic strains and maintain oral health benefits.

Summary

Probiotics have potential in the management of multifactorial diseases such as the periodontal diseases and caries, by more effectively addressing the host-microbial interface to restore homeostasis that may not be achieved with conventional treatments.

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Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case

[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patient...

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Long-term outcomes of endoscopic submucosal dissection in comparison to surgery in undifferentiated-type intramucosal gastric cancer using propensity score analysis

Abstract

Background

The treatment of intramucosal early gastric cancer with undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal dissection (ESD) is controversial. This study aimed to compare the clinical and oncologic long-term outcomes of ESD and surgery for UD-EGCs.

Methods

A prospectively collected database of patients who underwent ESD or surgery between January 2006 and December 2012 was established. Patients who diagnosed with UD-EGC and satisfied the expanded indications of ESD were included. Clinical data from 111 patients treated with ESD and 382 patients underwent surgery were analyzed, and 1–1 propensity score-matched 81 pairs of patients were also compared.

Results

In both groups, two-thirds of the UD-EGCs had signet ring cell (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After propensity score-matched, case-matching covariates were not significantly different between the groups. Disease-free survival (DFS) was significantly shorter in the ESD group, but overall survival (OS) was not different between the two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According to histologic type, OS of SRC histology was not different between the group, both in overall comparison and propensity score-matched analysis (P = 0.286 and P = 0.210). On the other hands, OS of poorly differentiated adenocarcinoma was significantly shorter in ESD group in overall comparison (P = 0.007), but was not as so in propensity score-matched analysis (P = 0.088).

Conclusions

ESD might be a complementary option for the treatment of UD-EGCs, especially in those with SRC-type histology based on strict expanded indications. Nonetheless, close endoscopic surveillance is required because of a high incidence of intragastric recurrence.

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Validation of the VBLaST pattern cutting task: a learning curve study

Abstract

Background

Mastery of laparoscopic skills is essential in surgical practice and requires considerable time and effort to achieve. The Virtual Basic Laparoscopic Skill Trainer (VBLaST-PC^©) is a virtual simulator that was developed as a computerized version of the pattern cutting (PC) task in the Fundamentals of Laparoscopic Surgery (FLS) system. To establish convergent validity for the VBLaST-PC^©, we assessed trainees' learning curves using the cumulative summation (CUSUM) method and compared them with those on the FLS.

Methods

Twenty-four medical students were randomly assigned to an FLS training group, a VBLaST training group, or a control group. Fifteen training sessions, 30 min in duration per session per day, were conducted over 3 weeks. All subjects completed pretest, posttest, and retention test (2 weeks after posttest) on both the FLS and VBLaST^© simulators. Performance data, including time, error, FLS score, learning rate, learning plateau, and CUSUM score, were analyzed.

Results

The learning curve for all trained subjects demonstrated increasing performance and a performance plateau. CUSUM analyses showed that five of the seven subjects reached the intermediate proficiency level but none reached the expert proficiency level after 150 practice trials. Performance was significantly improved after simulation training, but only in the assigned simulator. No significant decay of skills after 2 weeks of disuse was observed. Control subjects did not show any learning on the FLS simulator, but improved continually in the VBLaST simulator.

Conclusions

Although VBLaST^©- and FLS-trained subjects demonstrated similar learning rates and plateaus, the majority of subjects required more than 150 trials to achieve proficiency. Trained subjects demonstrated improved performance in only the assigned simulator, indicating specificity of training. The virtual simulator may provide better opportunities for learning, especially with limited training exposure.

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Robotic ventral hernia repair is not superior to laparoscopic: a national database review

Abstract

Background

Minimally invasive surgery (MIS) use for ventral hernia repair has increased over the last decade. Whether outcomes are improved by robotic assistance remains a subject of debate. The aim of this study is to evaluate outcomes (including cost, complications, length of stay (LOS), and pain medication utilization) in patients who underwent an open (OVHR), laparoscopic (LVHR), or robotic (RVHR) ventral hernia repair (VHR).

Methods

The Vizient database was queried using ICD-9 procedure and diagnosis codes for patients who underwent VHR from January 2013 to September 2015. Complications, 30-day readmission, mortality, LOS, cost, and intra-hospital opiate utilization were analyzed using IBM SPSS v.23.0.0.0. Median tests with post hoc pairwise comparisons, Fischer's exact, and Pearson's chi-squared test with Bonferroni correction were applied where appropriate, with α = 0.05.

Results

46,799 patients (OVHR: N = 39,505, LVHR: N = 6829, RVHR: N = 465) met the criteria and patients in each group had similar demographics (Table 1). OVHR was associated with significant increased overall complications, 30-day readmission, LOS, and postoperative pain use compared to RVHR or LVHR. OVHR had higher mortality and postoperative infection rates than LVHR. RVHR had significantly higher rates of complications and postoperative infections compared to LVHR, although there was no difference in mortality, 30-day readmission, LOS, and postoperative pain medication use. Mean direct cost of surgery was significantly higher for RVHR, followed by OVHR and LVHR.

Conclusions

Overall patient outcomes were improved in the LVHR and RVHR groups compared to the open approach. However, RVHR patients did not have significant improvement compared with the LVHR group in either short-term outcomes or opiate medication used. While RVHR surgery was the most expensive modality, OVHR was also significantly costlier than LVHR, which was the least expensive. Long-term data on recurrence could not be evaluated and should be studied to determine the role of robotic surgery in VHR and recurrence rates.

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Long-term clinical outcomes after intrathoracic stomach surgery: a decade of longitudinal follow-up

Abstract

Background

A subset of patients with large paraesophageal hernias have more than 75% of the stomach herniated above the diaphragm; such cases are referred to as intrathoracic stomach (ITS). Herein, we report longitudinal symptomatic outcomes over a decade after surgical ITS repair in a large patient cohort.

Methods

Patients who underwent surgical treatment for ITS from 01/2004 to 05/2016 were studied. Preoperative and follow-up data were prospectively collected. Patients completed a standardized symptom questionnaire 1 year postoperatively and at 2-year intervals thereafter.

Results

In total, 235 patients were reviewed. The mean age was 70.0 ± 11.6 years; 174 patients (74.0%) were women. Surgical procedures included 7 transthoracic repairs and 228 transabdominal repairs (222 laparoscopic, 2 open, 4 laparoscopic-to-open conversions). Anti-reflux procedures were performed in 173 patients (73.6%). 33 patients (14.0%) had mesh reinforcement of hiatal closure; 11 (4.7%) underwent Collis gastroplasty. Follow-up symptom questionnaires at 1, 3, 5, 7, 9, and 11 years were available for 81, 48, 47, 30, 33, and 38% of patients, respectively. Significant and lasting symptom improvement was reported at all follow-up time points. Mean satisfaction scores of 9.3, 9.1, 9.3, 9.0, 9.5, and 9.8 on a 1–10 scale were recorded at the aforementioned intervals.

Conclusions

Long-term clinical outcomes confirm that laparoscopic ITS repair is safe and durable, and is associated with a high degree of patient satisfaction and symptom resolution.

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A Systematic review and meta-analysis of the efficacy and safety of video-assisted anal fistula treatment (VAAFT)

Abstract

Background

Video-assisted anal fistula treatment (VAAFT) is a novel, minimally invasive technique for the treatment of fistula-in-ano (FIA). This review aimed to search the literature for the outcome of VAAFT regarding the recurrence and complication rates of the technique.

Methods

A systematic literature search was conducted in compliance with the PRISMA screening guidelines. PubMed/MEDLINE and Scopus were searched for articles reporting the outcomes of VAAFT procedure from inception through April 2017. The main outcomes were patients' characteristics, technical aspects, operation time, recurrence, and complication rates.

Results

Eleven studies (n = 788 patients) were included. The mean age of the patients was 39.5 years. 66.5% of patients had high or complex FIA and 18.4% underwent previous fistula surgery. The internal opening of the fistula was detected in 85.7% of patients. The mean operation time was 42 ± 14.2 min. The weighed mean rate of detection of internal opening was 93.3%. Recurrence occurred in 112 (14.2%) patients after a median follow-up of 9 months. Recurrence rates varied according to method of closure of internal opening from 15.3% after using staplers, 17.7% after suturing, to 25% after advancement flap. The weighted mean recurrence rate across the studies was 17.7%. The weighted mean complication rate was 4.8%.

Conclusion

VAAFT may be considered an effective diagnostic tool and a safe method for the treatment of complex and high FIA attaining satisfactory outcome and acceptably low complications. Recurrence after VAAFT may be related to previous fistula surgery and the method of closure of the internal opening.

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Determinants of variability in management of acute calculous cholecystitis

Abstract

Background

While evidence supports early compared to delayed cholecystectomy as optimal management of acute calculous cholecystitis (ACC), significant variability in practice remains. The purpose of this study was to identify variables associated with early cholecystectomy, to target opportunities to improve adherence to best practices.

Methods

Adult patients admitted to surgical units with ACC at two hospitals in a university hospital network between June 2010 and January 2015 were reviewed. Patients with concurrent pancreatitis, cholangitis or severe ACC (with organ system failure) were excluded. Early cholecystectomy was defined as surgery performed during same admission and within 7 days of presentation. Non-operative management was defined as admission for ACC treated conservatively, with or without eventual delayed cholecystectomy. The primary outcome was early cholecystectomy versus initial non-operative management; secondary outcomes included time to cholecystectomy, complications, and total hospital length of stay (LOS).

Results

A total of 374 patients were included. Two hundred and forty six patients (66%) underwent early cholecystectomy, 60 (16%) were treated non-operatively and had delayed cholecystectomy, and 68 (18%) were only treated non-operatively. Median time to OR from initial presentation was 38 h [22–63] for early cholecystectomy patients and 69 days [29–116] for the non-operative patients who had delayed cholecystectomy. When comparing both groups, early cholecystectomy patients were younger and were treated more often at site 1. There were no differences in complications during hospitalization, but early cholecystectomy patients had a lower median total LOS (3 [2–5] vs. 5 [4–9], p < 0.001), and they had fewer gallstone-related events after discharge (1 vs. 18%, p < 0.001). On multiple logistic regression analysis, lower age, hospital site and lower risk of concurrent choledocholithiasis were all significantly associated with early cholecystectomy (p < 0.05).

Conclusion

Our data supports early cholecystectomy as best practice in management of ACC with no differences in complications during hospitalization, shorter median LOS and fewer gallstone-related events compared to non-operative management. We identified patient and institutional factors associated with early cholecystectomy. This suggests that multiple strategies will be necessary to promote adherence to best practices in the management of ACC within our institution.

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The feasibility of laparoscopic rectal resection in patients undergoing reoperation after transanal endoscopic microsurgery (TEM)

Abstract

Background

The success of transanal endoscopic microsurgery (TEM) for early rectal cancer depends on proper indications and strict patient selection. When unfavorable pathologic features are identified after TEM operation, total mesorectal excision is recommended to minimize the risk of recurrence. In this study, data were collected in a retrospective series of patients to determine the results of laparoscopic reoperation after TEM.

Methods

All patients underwent an accurate rectal-digital examination and clinical tumor staging by transanal endosonography, CT, and/or MRI. The histologic examination included an evaluation of the free margins, depth of tumor infiltration according to International Union Against Cancer guidelines, degree of tumor differentiation, and the presence of lymphovascular and perineural invasion. When a high-risk tumor was identified, reoperation was performed within 6 weeks from TEM. The patients were divided into two groups according to the procedure performed: laparoscopic anterior resection (LAR) or laparoscopic abdominal perineal amputation (LAPR).

Results

Sixty-eight patients (5.3%) underwent reoperation: 38 underwent LAR and 30 underwent LAPR. The mean operative time was 148.24 min (± 35.8, p = 0.62). Meanwhile, the mean distance of the TEM scar from the anal verge differed statistically between the two groups (p = 0.003) and was statistically correlated with abdominal perineal amputation (p = 0.0001) in multivariate analysis. Conversion to open surgery was required in 6 patients (15.7%) in the LAR group and 3 patients (10%) in the LAPR group (p = 0.38). The histologic examination revealed residual cancer cells in 3 cases (3 pT2N0) and 1 case (1 pT3N0), respectively, and lymph node metastases in 4 cases. No residual neoplasms were detected in the remaining 60 cases (88.3%). After a mean follow-up of 108 months, the overall disease-free survival was 98% (95% CI 88–99%).

Conclusions

In our experience, reoperation after TEM using a laparoscopic approach is feasible and safe, with low conversion rates and optimal postoperative results.

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Endoscopic treatment of leaks after laparoscopic sleeve gastrectomy using MEGA esophageal covered stents

Abstract

Background

Sleeve gastrectomy has become one of the main bariatric procedures over the last few years. This can be explained by the relative simplicity and high effectiveness of this method. Yet, it causes complications as any other method. Staple line leaks are the most frequent ones. According to different sources, this complication may occur with 0–7% frequency. Until 2013, surgery was the only effective treatment method for this complication. However, reoperations considerably increased treatment cost and patient morbidity. The aim of this study is to present the possibilities of endoscopic treatment of leaks after laparoscopic sleeve gastrectomy.

Methods

From 2014 to 2016 14, cases of leaks following sleeve gastrectomy were diagnosed in our Department in Łódź. All of them were treated with MEGA stent in order to cover the leak site. Due to severe peritonitis, 3 patients had to undergo surgery prior to implantation of the prosthesis. Another patient underwent an unsuccessful attempt of leak closing via OTSC method prior to implantation of the prosthesis. Patients were nourished from the 3rd day after the surgery. On average, prostheses were removed on the 34th day after the implantation.

Results

The leak was fully sealed in 13 out of 14 cases. In 10 cases the leak was fully healed. There were 2 cases of patients' deaths: the result of a multi-organ failure in one case and early esophageal perforation in the other one. The overall success rate was 90.9%.

Conclusion

Sealing leaks occurring after sleeve gastrectomy with MEGA stents represent an effective method and should become the technique of choice.

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Comparison of two new techniques for the management of malignant central airway obstruction: argon plasma coagulation with mechanical tumor resection versus cryorecanalization

Abstract

Background

The development of central airway obstruction during malignant diseases is an important cause of morbidity and mortality. Endobronchial therapies can decrease the patient's symptoms and improve quality of life. Here, we compare airway recanalization methods: argon plasma coagulation with mechanical tumor resection (APC + MTR) and cryorecanalization (CR efficiency, complications, restenosis rate, and time to restenosis) in patients with malignant exophytic endobronchial airway obstruction.

Methods

A total of 89 patients were included who were admitted to our hospital between 2005 and 2012. The data were analyzed retrospectively. Initially, a CR procedure was performed in 52 patients using rigid bronchoscopy under general anesthesia; the APC + MTR procedure was performed in 37 patients with malignant airway obstruction.

Results

The airway patency rate with APC + MTR was 97.3% (n = 36) and CR was 80.8% (n = 42). The APC + MTR procedure was more effective than CR for recanalization of malignant endobronchial exophytic airway obstruction. Additionally, the achievement rate of airway patency with APC + MTR was significantly higher in tumors with distal bronchial involvement. There was no statistically significant difference between groups in terms of complications, restenosis rate, and time to restenosis.

Conclusions

The APC + MTR procedure is preferred over CR to introduce and maintain airway patency in patients with malignancy-related endobronchial exophytic airway obstruction.

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Robotic single-site versus multiport laparoscopic cholecystectomy: a case-matched analysis of short- and long-term costs

Abstract

Background

Multiport laparoscopy is the gold-standard approach for cholecystectomy, and single-port laparoscopy has been developed to further reduce its invasiveness. A specific robotic single-port platform (da Vinci single-site, Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2011, which could technically facilitate single-site cholecystectomy. Current data show its feasibility; however, detailed short- and long-term analyses of costs and comparisons relative to multiport laparoscopy are not available to date.

Methods

Patients who underwent robotic single-site cholecystectomy for benign, clinically noninflammatory disease between 2011 and 2015 were matched for disease, age, gender, BMI, ASA classification, diagnosis, and elapsed year of surgery to a cohort of multiport cholecystectomies. Demographic, perioperative, and long-term data were collected retrospectively and analyzed. Perioperative and long-term costs including re-operations due to the primary procedure until February 2017 were compared across both cohorts.

Results

99 patients who underwent robotic single-site cholecystectomy were matched to 99 patients with multiport cholecystectomy. A higher rate of outpatient procedures in the robotic cohort (31.3 vs. 17.2%, p = 0.0305) was found, and demographic parameters and perioperative clinical outcomes were similar. Perioperative costs were significantly higher for the robotic single-site patients (6158.0 vs. 4288.0 USD, p < 0.0001). With similar follow-up times of 59.0 and 58.9 months, respectively (p = 0.9552), significantly more patients of the robotic Single-Site cohort underwent follow-up surgery (7.1 vs. 0.0%, p = 0.0140), and follow-up costs were significantly higher for the robotic cohort (694.7 vs. 0.0 USD, p = 0.0145).

Conclusion

With similar early postoperative clinical results and a higher rate of re-operations, perioperative and long-term costs are significantly higher with robotic Single-Site cholecystectomy compared with multiport cholecystectomy. Considering the unclear clinical value of robotic single-site cholecystectomy and the significant short- and long-term costs, a call for further research and a debate as to who should bear the costs beyond the ones of the gold-standard treatment appear reasonable.

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Concomitant open ventral hernia repair: what is the financial impact of performing open ventral hernia with other abdominal procedures concomitantly?

Abstract

Background

Open ventral hernia repair (VHR) is often performed in conjunction with other abdominal procedures. Clinical outcomes and financial implications of VHR are becoming better understood; however, financial implications of concomitant VHR during other abdominal procedures are unknown. This study aimed to evaluate the financial implications of adding VHR to open abdominal procedures.

Methods

This IRB-approved study retrospectively reviewed hospital costs to 180-day post-discharge of standalone VHRs, isolated open abdominal surgeries (bowel resection or stoma closure, removal of infected mesh, hysterectomy or oophorectomy, panniculectomy or abdominoplasty, open appendectomy or cholecystectomy), performed at our institution from October 1, 2011 to September 30, 2014. The perioperative risk data were obtained from the local National Surgery Quality Improvement Program (NSQIP) database, and resource utilization data were obtained from the hospital cost accounting system.

Results

345 VHRs, 1389 open abdominal procedures as described, and 104 concomitant open abdominal and VHR cases were analyzed. The VHR-only group had lower ASA Class, shorter operative duration, and a higher percentage of hernias repaired via separation of components than the concomitant group (p < 0.001). The median hospital cost for VHR-alone was $12,900 (IQR: $9500–$20,700). There were significant increases to in-hospital costs when VHR was combined with removing an infected mesh (63%) or with bowel resections or stoma closures (0.7%). The addition of VHR did not cause a significant change in 180-day post-discharge costs for any of the procedures.

Conclusions

This study noted decreased costs when combining VHR with panniculectomy or abdominoplasty and hysterectomy or oophorectomy. For removal of infected mesh and bowel resection or stoma closure, waiting, when feasible, is recommended. Given the impending changes in financial reimbursements in healthcare in the United States, it is prudent that future studies evaluate further the clinical and fiscal benefit of concomitant procedures.

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Laparoscopy for primary cytoreduction with multivisceral resections in advanced ovarian cancer: prospective validation. “The times they are a-changin”?

Abstract

Background

Primary cytoreduction is the mainstay of treatment for advanced ovarian cancer (AOC). We developed and prospectively evaluated an algorithm to investigate the possible role of laparoscopic primary cytoreduction (LPC) in carefully selected patients, with AOC.

Methods

From June 2007 to July 2015, all patients with stage III–IV ovarian cancer and clinical conditions allowing aggressive surgery were candidate to primary cytoreduction with the aim of achieving residual tumor (RT) = 0. The possibility of attempting laparoscopic cytoreduction was carefully evaluated using strict selection criteria. The other patients were approached by abdominal primary cytoreduction (APC). At the end of LPC, an ultra-low pubic mini-laparotomy was performed to extract surgical specimens and to accomplish a laparoscopic hand-assisted exploration of the abdominal organs, in order to confirm complete excision of the disease.

Results

Of the included 66 patients, 21 were considered eligible for LPC; the remaining 45 underwent APC. Optimal cytoreduction (i.e., RT = 0) was obtained in 95 and 88.4% in the LPC and APC groups, respectively. No intra-operative complication and 4 (19%) early post-operative complications were observed among patients who received LPC. Patients who underwent APC had 17.8 and 46.7% intra- and early post-operative complications, respectively. Median time to initiation of chemotherapy was 15 (range, 10–30) days in the LPC group and 28 (20–35) days in the APC group. After a median follow-up of 51 months, 2-year disease-free survival was 76.2% in the LPC group and 73.4% in the APC group.

Conclusions

After strict selection, a group of patients with AOC may undergo LPC with extremely high rates of optimal cytoreduction, satisfactory perioperative morbidity, a short interval to chemotherapy, and encouraging survival outcomes.

Clinical trial registration NCT02980185

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How much pain relief do patients expect after cholecystectomy?

Abstract

Background

Cholecystectomy is a common operation, increasingly performed, in the USA, for "functional gall bladder disorder" (FGBD). Outcomes of these surgeries are uncertain. In planning a study of FGBD, we needed to define the best outcome measures.

Methods

We sought the opinions of patients (52 with FGBD and 100 with stones for comparison) coming to cholecystectomy. They were asked to respond in four ways about the minimum benefit they would count as "success."

Results

We found that most patients do not expect cholecystectomy to relieve their pain-related disability completely, regardless of the presence or absence of stones.

Conclusions

Future studies of the success of surgery should use patient-centered outcome assessments, such as PGIC (patient's global impression of change), in addition to objective measures of the impact of treatment on key symptoms, such as pain.

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Array-based sequencing of filaggrin gene for comprehensive detection of disease-associated variants

Publication date: Available online 19 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): X. F. Colin C. Wong, Simon L.I.J. Denil, Jia Nee Foo, Huijia Chen, Angeline Su Ling Tay, Rebecca L. Haines, Mark B.Y. Tang, W. H. Irwin McLean, Aileen Sandilands, Frances J.D. Smith, E. Birgitte Lane, Jianjun Liu, John E.A. Common

Teaser

Comprehensive sequencing of FLG is a challenging endeavour. We have developed a method using array-based amplicon PCR and NGS for a robust and cost efficient method to analyze this major atopic dermatitis risk factor.

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PLDT (planarian light/dark test): an invertebrate assay to quantify defensive responding and study anxiety-like effects

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Ashenafi Mebratu Zewde, Frances Yu, Sunil Nayak, Christopher Tallarida, Allen B. Reitz, Lynn G. Kirby, Scott M. Rawls
BackgroundPlanarians, like rodents, instinctively spend more time in dark versus light environments when given a choice. This behavioral phenomenon is called negative phototaxis, which may reflect defensive responding related to an anxiety-like phenotype.New methodWe propose a planarian light/dark test, designated PLDT, to predict anxiogenic- or anxiolytic-like effects. Experimentally, we placed a planarian at the midline of a Petri dish, containing test compound or water, that was split evenly into light and dark compartments and determined time spent in the light over 10min.ResultsA clinically-approved benzodiazepine agonist (clorazepate; 10μM) increased time spent in the light whereas an inverse benzodiazepine agonist (FG-7142; 1, 10μM) produced the opposite response. Fluoxetine (1μM) or ethanol (1%), as well as the 'bath salt' cathinone S-mephedrone (300μM), enhanced time spent in the light. Planarians exposed to predator (frog) odor spent more time in the dark.Comparison with existing methodsThe light/dark box (LDB) test in rodents is used to screen putative medications for possible anxiolytic and anxiogenic effects. Our results showing that time spent in the light by planarians is enhanced by common anxiety-relieving drugs (e.g. benzodiazepine agonist, ethanol, fluoxetine) and decreased by anxiogenic substances (e.g. predator odor, benzodiazepine inverse agonist) reveal directionally similar effects in the established (LDB) and new (PLDT) assays.ConclusionOur data identify the PLDT as a cost-effective, invertebrate assay for quantifying the effects of practically any water-soluble substance on defensive responding and for studying and teaching anxiety-like responses in a living organism.

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Vértigo posicional paroxístico benigno: criterios diagnósticos. Documento de consenso del Comité para la Clasificación de los Trastornos Vestibulares de la Bárány Society

Publication date: Available online 19 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Michael von Brevern, Pierre Bertholon, Thomas Brandt, Terry Fife, Takao Imai, Daniele Nuti, David Newman-Toker
Este artículo presenta los criterios diagnósticos para el vértigo posicional paroxístico benigno (VPPB) formulados por el Comité para la Clasificación de los Trastornos Vestibulares de la Bárány Society. La clasificación refleja el estado actual del conocimiento acerca de los aspectos clínicos y los mecanismos patogénicos del VPPB e incluye tanto los síndromes bien establecidos como los emergentes. Se presupone que el conocimiento progresivo de la enfermedad conducirá a un desarrollo adicional de esta clasificación.This article presents operational diagnostic criteria for benign paroxysmal positional vertigo (BPPV), formulated by the Committee for Classification of Vestibular Disorders of the Bárány Society. The classification reflects current knowledge of clinical aspects and pathomechanisms of BPPV and includes both established and emerging syndromes of BPPV. It is anticipated that growing understanding of the disease will lead to further development of this classification.

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Neuroma in Axillary Dissection Scar Bed Following Mastectomy

This case demonstrates the successful use of percutaneous core biopsy sampling to provide definitive diagnosis of traumatic neuroma, which is unusual in post-mastectomy patients.
Applied Radiology

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Clinicopathologic implications of CD8 + /Foxp3 + ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients

Abstract

Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3⁺, CD8⁺, PD-1⁺ and PD-L1⁺) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients. MiRNAs microarray and bioinformatical analysis were used to identify miRNAs potentially regulating PD-L1 expression, which were further validated by quantitative RT-PCR. miR-574-3p was identified to potentially regulate PD-L1 expression in chordoma, which inversely correlated with PD-L1. Positive PD-L1 expression on tumor cells was associated with advanced stages (P = 0.041) and TILs infiltration (P = 0.005), whereas decreased miR-574-3p level correlated with higher muscle invasion (P = 0.012), more severe tumor necrosis (P = 0.022) and poor patient survival. Importantly, a patient subgroup with PD-L1⁺/miR-574-3p^low chordoma phenotype was significantly associated with worse local recurrence-free survival (LRFS) (P = 0.026). PD-1⁺ TILs density was associated with surrounding muscle invasion (P = 0.014), and independently portended poor LRFS (P = 0.040), while PD-L1⁺ TILs showed tendencies of less aggressive clinical outcomes. Multivariate analysis of OS only found CD8⁺/Foxp3⁺ ratio to be independent prognostic factor (P = 0.022). These findings may be useful to stratify patients into prognostic groups and provide a rationale for the use of checkpoint blockade therapy, possibly by administering miR-574-3p mimics, in spinal chordoma.

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Correlation between the pain numeric rating scale and the 12-item WHO Disability Assessment Schedule 2.0 in patients with musculoskeletal pain.

Objective: The aim of this study was to assess the correlation between pain severity measured on a numeric rating scale and restrictions of functioning measured with the WHO Disability Assessment Schedule (WHODAS 2.0). Patients and methods: This was a cross-sectional study of 1207 patients with musculoskeletal pain conditions. Correlation was assessed using Spearman's and Pearson tests. Results: Although all the Spearman's rank correlations between WHODAS 2.0 items and pain severity were statistically significant, they were mostly weak, with only a few moderate associations for 'S2 household responsibilities', 'S8 washing', 'S9 dressing', and 'S12 day-to-day work'. The correlation between the WHODAS 2.0 total score and pain severity was also moderate: 0.41 [95% confidence interval (CI): 0.36-0.45] for average pain and 0.42 (95% CI: 0.37-0.46) for worst pain. The correlation between the WHODAS 2.0 total score and pain level was also assessed using Pearson's product-moment correlation, yielding figures that were similar to Spearman's correlation: 0.42 (P

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Clinicopathologic implications of CD8 + /Foxp3 + ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients

Abstract

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Clinicopathologic implications of CD8 + /Foxp3 + ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients

Abstract

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Symbol Grounding Without Direct Experience: Do Words Inherit Sensorimotor Activation From Purely Linguistic Context?

Abstract

Theories of embodied cognition assume that concepts are grounded in non-linguistic, sensorimotor experience. In support of this assumption, previous studies have shown that upwards response movements are faster than downwards movements after participants have been presented with words whose referents are typically located in the upper vertical space (and vice versa for downwards responses). This is taken as evidence that processing these words reactivates sensorimotor experiential traces. This congruency effect was also found for novel words, after participants learned these words as labels for novel objects that they encountered either in their upper or lower visual field. While this indicates that direct experience with a word's referent is sufficient to evoke said congruency effects, the present study investigates whether this direct experience is also a necessary condition. To this end, we conducted five experiments in which participants learned novel words from purely linguistic input: Novel words were presented in pairs with real up- or down-words (Experiment 1); they were presented in natural sentences where they replaced these real words (Experiment 2); they were presented as new labels for these real words (Experiment 3); and they were presented as labels for novel combined concepts based on these real words (Experiment 4 and 5). In all five experiments, we did not find any congruency effects elicited by the novel words; however, participants were always able to make correct explicit judgements about the vertical dimension associated to the novel words. These results suggest that direct experience is necessary for reactivating experiential traces, but this reactivation is not a necessary condition for understanding (in the sense of storing and accessing) the corresponding aspects of word meaning.

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Real Objects Can Impede Conditional Reasoning but Augmented Objects Do Not

Abstract

In this study, Knauff and Johnson-Laird's (2002) visual impedance hypothesis (i.e., mental representations with irrelevant visual detail can impede reasoning) is applied to the domain of external representations and diagrammatic reasoning. We show that the use of real objects and augmented real (AR) objects can control human interpretation and reasoning about conditionals. As participants made inferences (e.g., an invalid one from "if P then Q" to "P"), they also moved objects corresponding to premises. Participants who moved real objects made more invalid inferences than those who moved AR objects and those who did not manipulate objects (there was no significant difference between the last two groups). Our results showed that real objects impeded conditional reasoning, but AR objects did not. These findings are explained by the fact that real objects may over-specify a single state that exists, while AR objects suggest multiple possibilities.

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Semantic Information and the Syntax of Propositional Attitude Verbs

Abstract

Propositional attitude verbs, such as think and want, have long held interest for both theoretical linguists and language acquisitionists because their syntactic, semantic, and pragmatic properties display complex interactions that have proven difficult to fully capture from either perspective. This paper explores the granularity with which these verbs' semantic and pragmatic properties are recoverable from their syntactic distributions, using three behavioral experiments aimed at explicitly quantifying the relationship between these two sets of properties. Experiment 1 gathers a measure of 30 propositional attitude verbs' syntactic distributions using an acceptability judgment task. Experiments 2a and 2b gather measures of semantic similarity between those same verbs using a generalized semantic discrimination (triad or "odd man out") task and an ordinal (Likert) scale task, respectively. Two kinds of analyses are conducted on the data from these experiments. The first compares both the acceptability judgments and the semantic similarity judgments to previous classifications derived from the syntax and semantics literature. The second kind compares the acceptability judgments to the semantic similarity judgments directly. Through these comparisons, we show that there is quite fine-grained information about propositional attitude verbs' semantics carried in their syntactic distributions—whether one considers the sorts of discrete qualitative classifications that linguists traditionally work with or the sorts of continuous quantitative classifications that can be derived experimentally.

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Automated MicroSPECT/MicroCT Image Analysis of the Mouse Thyroid Gland

Thyroid , Vol. 0, No. 0.

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Role of Krüppel-Like Factor 4 in the Maintenance of Chemoresistance of Anaplastic Thyroid Cancer

Thyroid , Vol. 0, No. 0.

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Review of "Setting Performance Standards for Technical and Nontechnical Competence in General Surgery" by Szasz P, Bonrath EM, Louridas M, Fesco AB, Howe B, Fehr A, Ott M, Mack LA, Harris KA, Grantcharov TP in Ann Surg 266: 1-7, 2017 and "Beyond 'Measure Twice': New Performance Standards in Surgery" by Yule S in Ann Surg 266:8-9, 2017.

No abstract available

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13-93B3 Bioactive Glass: a New Scaffold for Transplantation of Stem Cell-Derived Chondrocytes.

Research using animal models gives human trials hope for recovery in many fields of regenerative medicine, although they are sometimes poor predictors for human experiences. Our goal was to investigate whether rat chondrocytes, differentiated from adipose-derived stem cells, could be transplanted using a new, easily shaped, bioactive glass scaffold, and to show the immunohistochemical results. Intraperitoneal and retroperitoneal adipose tissue was extracted from 6 male Wistar albino type rats. The fatty tissue samples were fragmented and incubated. Chondrogenic differentiation was carried out and collagen type II, bFGF, and Sox-9 immunohistochemical characterization analysis was performed. Differentiated chondrocytes were implanted on 13-93B3 bioactive glass scaffolds and transplanted into the right ears of the rats. As control, only the biomaterial was transplanted into the left ears of the rats. After 1 month, the rats were sacrificed and transplantation areas were examined immunohistochemically. Histological examination of control samples from the left ears revealed that the biomaterial was covered with connective tissue, its general structure was preserved, and resorption of the scaffold had started. In specimens from the right ears, the biomaterial was covered with connective tissue, its structure was preserved, cartilage cells were present around the biomaterial, and the presence of cartilage tissue was demonstrated immunohistochemically. In conclusion, 13-93B3 bioactive glass scaffold contributed to the formation of new collagen and the survival of chondrocytes, and is a promising new biomaterial that will prove very useful in regenerative medicine. (C) 2017 by Mutaz B. Habal, MD.

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Hemodynamic Changes in Paramedian Forehead Flap.

Paramedian forehead flap is a workhorse for nasal reconstruction. However, vascular complications may lead to flap failure. The purpose of this study was to evaluate the blood flow objectively and determine the hemodynamic changes in paramedian forehead flap with respect to influential factors of age, gender, and smoking. Thirty patients who had paramedian forehead flap were followed up prospectively between 2010 and 2013. The blood flow was assessed by resistance index using Color Duplex-Doppler Ultrasonography. Resistance index was measured at the proximal and distal ends of each flap on the postoperative first day, first week, and second week. All data were analyzed using SPSS 15.0 for Windows. Fifteen patients were female and the mean of age was 60.9 years. Our results demonstrated statistically significant differences with gradual decreases in resistance to blood flow, when the resistance index values at the proximal and distal ends of paramedian forehead flap were compared (P

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The Etiology of Neuronal Development in Craniosynostosis: A Working Hypothesis.

Craniosynostosis is one of the most common craniofacial conditions treated by neurologic and plastic surgeons. In addition to disfigurement, children with craniosynostosis experience significant cognitive dysfunction later in life. Surgery is performed in infancy to correct skull deformity; however, the field is at a crossroads regarding the best approach for correction. Since the cause of brain dysfunction in these patients has remained uncertain, the role and type of surgery might have in attenuating the later-observed cognitive deficits through impact on the brain has been unclear. Recently, however, advances in imaging such as event-related potentials, diffusion tensor imaging, and functional MRI, in conjunction with more robust clinical studies, are providing important insight into the potential etiologies of brain dysfunction in syndromic and nonsyndromic craniosynostosis patients. This review aims to outline the cause(s) of such brain dysfunction including the role extrinsic vault constriction might have on brain development and the current evidence for an intrinsic modular developmental error in brain development. Illuminating the cause of brain dysfunction will identify the role of surgery can play in improving observed functional deficits and thus direct optimal primary and adjuvant treatment. (C) 2017 by Mutaz B. Habal, MD.

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Hydatid Cyst of the Parotid Gland: A Rare Location.

Hydatid disease of the parotid gland is a very rare entity and may be easily overlooked in the diagnosis of parotid masses. Although Turkey remains an endemic area for echinococcosis, involvement of the parotid gland is extremely rare. A 26-year-old man presented with primary parotid gland mass without any other organ involvement. During the first surgery, the cyst was perforated accidentally and in a short time recurrence was occurred. Maximum attention was given for the second surgery for total removal without damaging the cyst with medical treatment. The clinicians should take hydatid disease of parotid gland into consideration and great care must be given for not damaging the capsule of the cystic tumors in order to prevent recurrences. (C) 2017 by Mutaz B. Habal, MD.

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Outcomes of Titanium Mesh Cranioplasty in Pediatric Patients.

Purpose: Cranial defects in children have been repaired with various materials ranging from autologous bone to synthetic materials. There is little published literature on the outcomes of titanium mesh cranioplasty (TMC) in calvarial reconstruction in the pediatric population. This study evaluates a pediatric cohort who underwent calvarial defect reconstruction with titanium mesh and assesses the efficacy and outcomes of TMC. Methods: An Institutional Review Board approved retrospective review of patients

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Virtual Reality Model of the Three-Dimensional Anatomy of the Cavernous Sinus Based on a Cadaveric Image and Dissection.

Objective: Studying the three-dimensional (3D) anatomy of the cavernous sinus is essential for treating lesions in this region with skull base surgeries. Cadaver dissection is a conventional method that has insurmountable flaws with regard to understanding spatial anatomy. The authors' research aimed to build an image model of the cavernous sinus region in a virtual reality system to precisely, individually and objectively elucidate the complete and local stereo-anatomy. Methods: Computed tomography and magnetic resonance imaging scans were performed on 5 adult cadaver heads. Latex mixed with contrast agent was injected into the arterial system and then into the venous system. Computed tomography scans were performed again following the 2 injections. Magnetic resonance imaging scans were performed again after the cranial nerves were exposed. Image data were input into a virtual reality system to establish a model of the cavernous sinus. Observation results of the image models were compared with those of the cadaver heads. Results: Visualization of the cavernous sinus region models built using the virtual reality system was good for all the cadavers. High resolutions were achieved for the images of different tissues. The observed results were consistent with those of the cadaver head. The spatial architecture and modality of the cavernous sinus were clearly displayed in the 3D model by rotating the model and conveniently changing its transparency. Conclusion: A 3D virtual reality model of the cavernous sinus region is helpful for globally and objectively understanding anatomy. The observation procedure was accurate, convenient, noninvasive, and time and specimen saving. (C) 2017 by Mutaz B. Habal, MD.

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Skull Base Neuroendoscopic Training Model Using a Fibrous Injectable Tumor Polymer and the Nico Myriad.

The Myriad is an innovative, high precision tool for tumor resection, designed to work within narrow endoscopic corridors. Due to its application in technically demanding situations, the learning curve associated with its use might be extremely challenging and time-consuming. The authors describe the application of an already validated training model, the skull base injectable tumor model (ITM), to allow trainees to practice with the use of the Myriad during endoscopic skull base procedures. A formalin embalmed cadaveric head was used for technical assessment. Stratathane resin ST-504 derived polymer was injected to mimic skull base tumors and Myriad was used for tumor resection during different endoscopic procedures. An endoscopic endonasal transsphenoidal, a trans-planum trans-tuberculum, and a trans-clival approach have been performed after ITM injection. The Myriad was used for tumor debulking and blunt manipulation, qualitatively evaluating the technical challenges in performing the surgical dissection. Injectable tumor model demonstrates to be a valuable educational tool to train surgeons in the use of Myriad, potentially speeding up the learning curve in the acquirement of necessary technical skills in manipulating the instrument, even in case of demanding surgical situation. (C) 2017 by Mutaz B. Habal, MD.

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A Modification to the Nasal Septal Chain Suture Which Improves Its Application.

Introduction: A novel modification to the nasal septal chain suture which makes its application easier and faster without using any special surgical instrument has been described in this study. The advantage of the modification was evaluated in terms of the suture application time. Methods: A total of 40 patients with a mean age of 30.1 +/- 10.6 (18-58) years were evaluated in 2 groups. A nasal septal chain suture was applied with the previously described technique and the new modification for each group after the patients underwent septoplasty. The suture application time for all of the patients was recorded. Results: The mean suture application time was 455.2 +/- 36.5 (380-530) seconds in the previous technique group and 404.7 +/- 29.4 (340-450) seconds in the modified technique group. The use of new modification of the technique was found to shorten the suture application time significantly (P

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Metopism: a Study of the Persistent Metopic Suture.

Metopism, the persistence of the metopic suture in adulthood, is a clinically significant radiographic finding. In addition to masquerading as a fracture of the frontal bone, a persistent metopic suture may be associated with other clinically significant anatomical variations including frontal sinus abnormalities. Several geographically and craniofacially distinct populations have yet to be assessed for the prevalence of metopism. This study aimed to determine the prevalence of metopic sutures in adult crania of diverse populations among which scant research exists. A total of 505 adult crania were examined for the presence of a metopic suture. A total of 13 (2.57%) demonstrated metopism. Among subpopulations, metopism was present in 8.06% (5:62) of European crania, 15.38% (2:13) of East Asian crania, 2.20% (2:91) of Egyptian crania, and 2.86% (1:35) of Bengali crania. Metopism was also found in 1 Chilean, Roman, and Tchuktchi cranium, respectively. Metopism was not seen in crania from individuals of African (non-Egyptian) descent (0:62), Peruvians (0:144), Malayans (0:23), or Mexicans (0:23). Among sexes, metopism was present in 3.77% (8:212) of females and 1.79% (5:279) of males. The prevalence of metopism differs between populations and sexes. The results of this study provide anthropological, developmental, and clinical insight with regard to metopism. (C) 2017 by Mutaz B. Habal, MD.

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Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema

Abstract

Objective

Patients with intracerebral hemorrhage (ICH) may elaborate varying degrees of perihematomal edema (PHE), requiring closer monitoring and a higher intensity of treatment. Here, we explore whether the soluble form of CD163, a scavenger receptor responsible for hemoglobin sequestration, can serve as a prognostic biomarker of PHE development and poor outcome after ICH.

Methods

Our study cohort was comprised of 51 primary age- and sex-matched ICH patients with moderate-sized, hypertensive deep hemorrhages. Patients were part of a prospective ICH registry cataloguing admission data along with functional outcomes. We measured sCD163 levels in serial serum and cerebrospinal fluid (CSF) samples obtained at prespecified timepoints. Descriptive statistics, including a generalized estimating equation for longitudinal data, were used to analyze sCD163 in relation to ICH outcomes.

Results

Acute serum sCD163 (<48 h postictus) was significantly elevated in ICH patients compared to both acute neurological event controls (P = <0.001) and healthy controls (P = 0.003). As predicted, acute serum sCD163 levels were significantly associated with both hematoma volume expansion (P = 0.009) and PHE expansion (P = 0.002). Further examination determined that patients with high PHE expansion had poorer modified Rankin Scale scores at discharge (P = 0.024), and circulating sCD163 levels were found to be significantly lower in patients with high-level PHE expansion.

Interpretation

Acute sCD163 levels may be a useful biomarker for the acute identification of patients at risk for hematoma expansion, perihematomal edema expansion and poorer short-term outcomes.

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Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease

Abstract

Objective

To evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD).

Methods

530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and LRRK2 PD; and features were compared between IPD and LRRK2 PD separately for men and women.

Results

Among IPD: men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS-IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among LRRK2 PD: Male predominance was not observed among G2019S LRRK2 cases. Women had worse UPDRS-IV but better olfaction. Among same sex: LRRK2 men and women had better olfaction than IPD counterparts. LRRK2 men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and LRRK2 women had greater UDPRS-IV and rates of dyskinesia.

Interpretation

There were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by LRRK2, with LRRK2 men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in LRRK2 and IPD should consider gender stratification in design or analysis.

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ANGIOGENIC AND OSTEOGENIC POTENTIALS OF DENTAL STEM CELLS IN BONE TISSUE ENGINEERING

Publication date: Available online 19 October 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Muhammad Fuad Hilmi Yusof, Wafa' Zahari, Siti Nurnasihah Md Hashim, Zul Faizuddin Osman, Hamshawagini Chandra, Thirumulu Ponnuraj Kannan, Khairul Bariah Ahmad Amin Noordin, Azlina Ahmad

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CCL26 participates in the PRL-3-induced promotion of colorectal cancer invasion by stimulating tumor-associated macrophage infiltration

Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAMs) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer (CRC) invasion and metastasis by inducing TAM infiltration remains unclear. In the present study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and CRC invasion and the underlying mechanism in CRC cells by overexpressing or silencing PRL-3. We found that PRL-3 up-regulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. Additionally, immunohistochemistry (IHC) analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV CRC tissues and were associated with a worse prognosis in CRC patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were co-cultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca2+of TAMs to increase the expression of IL-6 and IL-8. Additionally, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV CRC tissues and correlated with CCL26. Moreover, similar results were observed in vivo using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes CRC invasion and metastasis by up-regulating CCL26 to induce TAM infiltration.

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Combinatorial treatment with mTOR inhibitors and streptozotocin leads to synergistic in vitro and in vivo antitumor effects in insulinoma cells

Streptozotocin (STZ)-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), while targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately objective response rates to both treatments are limited. Since mTOR pathway activation, commonly observed in pNETs, has been reported as one of the major mechanisms accounting for chemoresistance, we investigated the potential benefit of mTOR inhibition combined with STZ treatment in a subset of pNETs, namely insulinomas. To evaluate the potential of mTOR inhibition in combination with STZ, we selected four different inhibitors acting at various levels of the pathway (everolimus: inhibition of mTORC1, MK-2206: inhibition of AKT, BKM120: inhibition of PI3K, mTORC1 and mTORC2, and BEZ235: inhibition of mTORC1 and mTORC2). Effects on cell viability and apoptosis were assessed in insulinoma cell lines INS-1E (rat) and MIN6 (mouse) in vitro and were confirmed in vivo by using a mouse model of hepatic tumor dissemination after intrasplenic xenograft. In vitro, all four combinations display synergistic effects. These combinations lead to heterogeneous mTOR pathway inhibition, in agreement with their respective target, and increased apoptosis. In vivo, tumor growth in the liver was significantly inhibited by combining STZ with everolimus (P=0.0014), BKM120 (P=0.0092) or BEZ235 (P=0.008) as compared to each agent alone. These results suggest that targeting the mTOR pathway in combination with STZ could be of potential benefit for insulinomas and pNET patients and thus support further clinical investigations.

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The Effect of Tackler Technique on Head Injury Assessment Risk in Elite Rugby Union.

Purpose: To use match video evidence of tackles in elite level rugby union in order to identify tackler proficiency characteristics, for both Lower Body and Upper Body Tackles, that result in Head Injury Assessments (HIA) for the tackler. Methods: A review of international rugby union matches (2013-2016) and Pro 12/ERC Champions Cup matches (2014-2016) from a professional rugby union club was conducted. HIA (n=53) and non-HIA tackles (n=233) were categorised as either front-on or side-on Upper Body or Lower Body Tackles and scored for tackling proficiency characteristics. A Chi-Square test (p

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Distribution of Elastic Fibers in the Lacrimal Sac and Nasolacrimal Duct of Japanese Cadavers.

Purpose: To investigate the distribution of elastic fibers in lacrimal sac and nasolacrimal duct of Japanese cadavers. Methods: We examined 8 lacrimal sacs and nasolacrimal ducts of 7 Japanese cadavers (4 right sides, 4 left sides; 3 mal es, 4 females; average age of 89 years at death) that were preserved with 10% buffered formalin. The harvested specimens were transversely sectioned. All specimens were stained with Elastica van Gieson. Micrographs were taken, and then converted to white and black images, and the elastic fiber density of 4 locations (middle and upper levels of lacrimal sac, and middle and lower levels of nasolacrimal duct) was compared. Results: Elastic fibers showed greater distribution in the lamina propria, compared with the submucosal tissue, at all locations (p

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Spontaneous Rupture of Lacrimal Gland Pleomorphic Adenoma: Pivotal Role in Masquerading Orbital Cellulitis.

The authors aim to report a 68-year-old patient presenting with acute swelling and redness of orbital area diagnosed initially as orbital cellulitis. Surgical excision was decided based on clinical and imaging findings with the diagnosis of pleomorphic adenoma of the lacrimal gland. Lacrimal gland pleomorphic adenoma usually presents with painless gradual swelling of upper eyelid. In an exceptionally rare circumstance, this case showed acute orbital inflammation, and imaging findings of orbital inflammation mostly focused around the cystic space of the lacrimal gland tumor. Histologic evaluation confirmed a ruptured cystic space of pleomorphic adenoma with foreign body-type inflammatory reaction. The authors propose spontaneous rupture of cystic space in the lacrimal gland pleomorphic adenoma as underlying mechanism for acute presentation of this tumor. Imaging and clinical characteristics and also prognostic implication of this phenomenon are discussed. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Acute Localized Exanthematous Pustulosis (ALEP): Review of Literature with Report of Case Caused by Amoxicillin-Clavulanic Acid

Abstract

Acute localized exanthematous pustulosis (ALEP) is a localized form of acute generalized exanthematous pustulosis, characterized by acute onset of multiple nonfollicular, pinhead-sized, sterile pustules following drug administration. Antibiotics, especially β-lactams and macrolides, have been implicated in the majority of cases, although eruption after nonsteroidal antiinflammatory drugs and many other medications has also been reported. Skin reaction arises quickly within a few hours, resolving rapidly within a few days without treatment, and it is usually accompanied by fever and neutrophilic leukocytosis. We report herein all cases of ALEP described in literature, adding the case of a 35-year-old woman admitted to our hospital with outbreak of erythematous pustules on her face, neck, and chest after amoxicillin–clavulanic acid treatment.

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Statin Use and Breast Cancer Prognosis in Black and White Women

Abstract

Studies show decreased risk of breast cancer recurrence and improved survival with statin use, but data on racial disparities regarding breast cancer prognosis and statin use are lacking. Our objective was to investigate if racial disparities in breast cancer prognosis can be partially explained by differences in pre-diagnosis statin use. Patients were identified from a prospective, multicenter study examining the effects of metabolic factors on breast cancer prognosis in Black and White women. Statin use, prognosis (as measured by Nottingham Prognostic Index), anthropometric, tumor, and socio-demographic characteristics were examined. Five hundred eighty-seven women (487 White, 100 Black) with newly diagnosed primary invasive breast cancer were recruited. Obesity was more prevalent in Black women than White women (47 vs 19%, p < 0.01); both groups had similar low-density lipoprotein (LDL) cholesterol levels (113 ± 41 vs 113 ± 36 mg/dl, p = 0.90). More Black women used statins than White women (18 vs 11%, p = 0.06). Black women had a worse prognosis in an adjusted model than White women (OR 2.13 95% CI 1.23–3.67). Statin use was not associated with prognosis in unadjusted (OR 1.03, 95% CI 0.53–2.0) and adjusted models (OR 1.14, 95% CI 0.56–2.31). In women with newly diagnosed breast cancer, Black women were more likely to be treated with statins than White women, contrary to previous studies. Black women had worse prognosis than White women, but this difference was not explained by differences in pre-diagnosis statin use. Our study suggests that differences in pre-diagnosis statin use do not contribute to racial disparities in breast cancer prognosis.

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Epithelial-to-mesenchymal transition antagonizes response to targeted therapies in lung cancer by suppressing BIM

Purpose: Epithelial-to-mesenchymal transition (EMT) confers resistance to a number of targeted therapies and chemotherapies. However, it has been unclear why EMT promotes resistance, thereby impairing progress to overcome it. Experimental Design: We have developed several models of EMT-mediated resistance to EGFR inhibitors (EGFRi) in EGFR mutant lung cancers to evaluate a novel mechanism of EMT-mediated resistance. Results: We observed that mesenchymal EGFR mutant lung cancers are resistant to EGFRi-induced apoptosis via insufficient expression of BIM, preventing cell death despite potent suppression of oncogenic signaling following EGFRi treatment. Mechanistically, we observed that the EMT transcription factor ZEB1 inhibits BIM expression by binding directly to the BIM promoter and repressing transcription. De-repression of BIM expression by depletion of ZEB1 or treatment with the BH3 mimetic ABT-263 to enhance "free" cellular BIM levels both led to re-sensitization of mesenchymal EGFR mutant cancers to EGFR inhibitors. This relationship between EMT and loss of BIM is not restricted to EGFR mutant cancers as it was also observed in KRAS mutant lung cancers and large datasets including different cancer subtypes. Conclusions: Altogether, these data reveal a novel mechanistic link between EMT and resistance to lung cancer targeted therapies.

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Liquid Biopsies Using Plasma Exosomal Nucleic Acids and Plasma Cell-Free DNA compared with Clinical Outcomes of Patients with Advanced Cancers

Purpose: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNA) originate from living cells, which can better reflect underlying cancer biology. Experimental Design: Next-generation sequencing (NGS) was used to test exosomal nucleic acids (exoNA), and droplet digital PCR (ddPCR) and BEAMing PCR were used to test cfDNA for BRAF V600, KRAS G12/G13, and EGFR exon19del/L858R mutations in 43 patients with progressing advanced cancers. Results were compared with clinical testing of archival tumor tissue and clinical outcomes. Results: Forty-one patients had BRAF, KRAS, or EGFR mutations in tumor tissue. These mutations were detected by NGS in 95% of plasma exoNA samples, by ddPCR in 92% of cfDNA samples, and by BEAMing in 97% cfDNA samples. NGS of exoNA did not detect any mutations not present in tumor, whereas ddPCR and BEAMing detected 1 and 2 such mutations, respectively. Compared with patients with high exoNA mutation allelic frequency (MAF), patients with low MAF had longer median survival (11.8 vs. 5.9 months; P=0.006) and time to treatment failure (7.4 vs. 2.2 months; P=0.009). A low amount of exoNA was associated with partial response and stable disease ≥6 months P=0.006). Conclusions: NGS of plasma exoNA for common BRAF, KRAS, and EGFR mutations has high sensitivity compared with clinical testing of archival tumor and testing of plasma cfDNA. Low exoNA MAF is an independent prognostic factor for longer survival.

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A multicenter phase I study evaluating dual PI3K and BRAF inhibition with PX-866 and vemurafenib in patients with advanced BRAF V600 mutant solid tumors

Purpose: The objectives of the study were to evaluate the safety of daily oral PX-866 in combination with twice daily vemurafenib and to identify potential predictive biomarkers for this novel combination. Experimental Design: We conducted a phase I, open-label, dose escalation study in patients with advanced BRAF V600 mutant solid tumors. PX-866 was administered on a continuous schedule in combination with vemurafenib. Patients underwent a baseline and on-treatment biopsy after 1-week of PX-866 monotherapy for biomarker assessment. Results: 24 patients were enrolled. The most common treatment-related adverse events were gastrointestinal side effects. One dose limiting toxicity (DLT) of grade 3 rash and one DLT of grade 3 pancreatitis were observed in cohort 2 (PX-866 6mg daily; vemurafenib 960mg twice daily) and cohort 3 (PX-866 8mg daily; vemurafenib 960mg twice daily), respectively. Of 23 response evaluable patients, 7 had confirmed partial responses (PRs), 10 had stable disease and 6 had disease progression. Decreases in intra-tumoral pAKT expression were observed following treatment with PX-866. Patients who achieved PRs had higher rates of PTEN loss by immunohistochemistry (80% vs 58%) and pathogenic PTEN mutations and/or deletions (57% vs 25%). Two patients with durable PRs had an increase in intra-tumoral CD8 T-cell infiltration following treatment with PX-866. Conclusions: PX-866 was well tolerated at its maximal tolerated single-agent dose when given in combination with a modified dose of vemurafenib (720mg twice daily). Response to treatment appeared to be associated with PTEN loss and treatment with PX-866 seemed to increase CD8 T-cell infiltration in some patients.

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The meta-analysis

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Impact of cartilage graft size on success of tympanoplasty

Abstract Introduction: In the last decade, there has been an increasing use of cartilage grafts in the primary repair of tympanic membrane perforations. The major advantages of cartilage are its stiffness and its very low metabolic requirements, which make it particularly suitable for difficult conditions, such as subtotal perforations, adhesive otitis and reoperation. Objective: To analyze the impact of different perforation sizes requiring different sizes of cartilage on the anatomical and functional outcome after tympanoplasty. Methods: Through this prospective non-controlled, non-randomized study, 50 patients underwent cartilage type 1 tympanoplasty (20 females and 30 males), with a mean age of 19.3 ± 9.8 years. According to size of perforation, patients were subdivided into three groups, Group I had perforation >50% of tympanic membrane area, in Group II patients the perforations were 25-50% of tympanic membrane area, and in Group III the perforations were ≤25% of tympanic membrane. All patients had pre and postoperative Pure Tone Average and Air Bone Gap frequencies (0.5, 1, 2, 4 kHz). All patients were followed up at least 12 months after operation. Results: The anatomical success rate among all patients was 92%, all groups showed statistical significant improvement between pre and postoperative air bone gap, no significant correlation between size of cartilage graft and degree of air bone gap improvement was noticed among the three groups. Conclusion: Size of a cartilage graft has no impact on degree of hearing improvement or anatomical success rate after tympanoplasty.

Resumo Introdução: Na última década, tem havido um interesse crescente no uso de enxertos de cartilagem como opção para o reparo de perfurações primárias de membrana timpânica. As principais vantagens da cartilagem são a sua rigidez e o metabolismo braditrófico, o que a torna particularmente adequada para condições difíceis, tais como perfurações subtotais, otite adesiva e reoperações. Objetivo: Analisar o impacto de diferentes tamanhos de perfuração, portanto diferentes tamanhos de cartilagem, sobre o desfecho anatômico e funcional da timpanoplastia. Método: Através deste estudo prospectivo, não controlado, não randomizado, 50 pacientes foram submetidos a timpanoplastia de cartilagem tipo 1 (20 mulheres e 30 homens), com idade média de 19,3 ± 9,8 anos. De acordo com o tamanho da perfuração, os pacientes foram subdivididos em três grupos, Grupo I com perfuração > 50% da área da membrana timpânica, Grupo II com perfuração de 25%-50% da área da membrana timpânica, Grupo III com perfuração ≤ 25% da membrana timpânica. Todos apresentavam Audiometria tonal pura pré e pós-operatório - gap Aéreo-Ósseo para frequências testadas (0,5, 1, 2, 4 kHz). Todos os pacientes foram acompanhados por pelo menos 12 meses após a cirurgia. Resultados: A taxa de sucesso anatômico entre todos os pacientes foi de 92%, todos os grupos apresentaram melhoria estatisticamente significante entre pré e pós-operatório nos três grupos, não houve correlação significante entre o tamanho do enxerto de cartilagem e observou-se algum grau de melhoria do gap nos 3 grupos. Conclusão: O tamanho do enxerto de cartilagem não tem impacto sobre o grau de melhoria da audição ou na taxa de sucesso anatômico após timpanoplastia.

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Encoding of speech sounds at auditory brainstem level in good and poor hearing aid performers

Abstract Introduction: Hearing aids are prescribed to alleviate loss of audibility. It has been reported that about 31% of hearing aid users reject their own hearing aid because of annoyance towards background noise. The reason for dissatisfaction can be located anywhere from the hearing aid microphone till the integrity of neurons along the auditory pathway. Objectives: To measure spectra from the output of hearing aid at the ear canal level and frequency following response recorded at the auditory brainstem from individuals with hearing impairment. Methods: A total of sixty participants having moderate sensorineural hearing impairment with age range from 15 to 65 years were involved. Each participant was classified as either Good or Poor Hearing aid Performers based on acceptable noise level measure. Stimuli /da/ and /si/ were presented through loudspeaker at 65 dB SPL. At the ear canal, the spectra were measured in the unaided and aided conditions. At auditory brainstem, frequency following response were recorded to the same stimuli from the participants. Results: Spectrum measured in each condition at ear canal was same in good hearing aid performers and poor hearing aid performers. At brainstem level, better F0 encoding; F0 and F1 energies were significantly higher in good hearing aid performers than in poor hearing aid performers. Though the hearing aid spectra were almost same between good hearing aid performers and poor hearing aid performers, subtle physiological variations exist at the auditory brainstem. Conclusion: The result of the present study suggests that neural encoding of speech sound at the brainstem level might be mediated distinctly in good hearing aid performers from that of poor hearing aid performers. Thus, it can be inferred that subtle physiological changes are evident at the auditory brainstem in a person who is willing to accept noise from those who are not willing to accept noise.

Resumo Introdução: Os aparelhos auditivos são prescritos para aliviar a perda de audibilidade. Tem sido relatado que 31% dos usuários rejeitam seu aparelho auditivo devido ao desconforto com o ruído de fundo. A razão para a insatisfação pode estar situada em qualquer local desde o microfone do aparelho auditivo até a integridade de neurônios ao longo da via auditiva. Objetivos: Medir espectros desde a saída do aparelho auditivo no nível do meato acústico externo e frequência de resposta (FFR) registrada no tronco encefálico de indivíduos com deficiência auditiva. Método: Foram selecionados 60 participantes com deficiência auditiva neurossensorial moderada, de 15 a 65 anos. Cada participante foi classificado como usuário bom ou mau de prótese auditiva (GHP ou PHP) com base na medida de nível de ruído aceitável (ANL). Estímulos/da/e/si/foram apresentados em alto-falante a 65 dB SPL. No meato acústico externo, os espectros foram medidos nas condições sem aparelho e com aparelho. No tronco encefálico auditivo, FFR foram registradas para os mesmos estímulos dos participantes. Resultados: Os espectros medidos em cada condição no meato acústico externo foram os mesmos em GHP e PHP. No nível do tronco cerebral, melhor codificação F0; energias de F0 e F1 foram significativamente maiores em GHP do que em PHP. Embora os espectros do aparelho auditivo fossem quase os mesmos entre GHP e PHP, existem variações fisiológicas sutis no tronco encefálico auditivo. Conclusão: O resultado do presente estudo sugere que a codificação neural do som da fala no nível do tronco encefálico pode ser mediada distintamente em GHP em comparação com PHP. Assim, pode-se inferir que mudanças fisiológicas sutis são evidentes no tronco encefálico em uma pessoa que está disposta a aceitar o ruído em comparação com aqueles que não estão dispostos a aceitar o ruído.

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Profile and prevalence of hearing complaints in the elderly

Abstract Introduction: Hearing is essential for the processing of acoustic information and the understanding of speech signals. Hearing loss may be associated with cognitive decline, depression and reduced functionality. Objective: To analyze the prevalence of hearing complaints in elderly individuals from Rio Grande do Sul and describe the profile of the study participants with and without hearing complaints. Methods: 7315 elderly individuals interviewed in their homes, in 59 cities in the state of Rio Grande do Sul, Brazil, participated in the study. Inclusion criteria were age 60 years or older and answering the question on auditory self-perception. For statistical purposes, the chi-square test and logistic regression were performed to assess the correlations between variables. Results: 139 elderly individuals who did not answer the question on auditory self-perception and 9 who self-reported hearing loss were excluded, totaling 7167 elderly participants. Hearing loss complaint rate was 28% (2011) among the elderly, showing differences between genders, ethnicity, income, and social participation. The mean age of the elderly without hearing complaints was 69.44 (±6.91) and among those with complaint, 72.8 (±7.75) years. Elderly individuals without hearing complaints had 5.10 (±3.78) years of formal education compared to 4.48 (±3.49) years among those who had complaints. Multiple logistic regression observed that protective factors for hearing complaints were: higher level of schooling, contributing to the family income and having received health care in the last six months. Risk factors for hearing complaints were: older age, male gender, experiencing difficulty in leaving home and carrying out social activities. Conclusions: Among the elderly population of the state of Rio Grande do Sul, the prevalence of hearing complaints reached 28%. The complaint is more often present in elderly men who did not participate in the generation of family income, who did not receive health care, performed social and community activities, had a lower level of schooling and were older.

Resumo Introdução: A audição é essencial para o processamento de eventos acústicos e emissão e compreensão dos sinais de fala. A perda auditiva pode estar associada ao declínio cognitivo, à depressão e à redução da funcionalidade. Objetivo: Analisar a prevalência de queixa auditiva em idosos do Rio Grande do Sul e descrever o perfil dos participantes com e sem queixa auditiva. Método: Participaram do estudo 7.315 idosos entrevistados em suas residências, em 59 cidades gaúchas. Os critérios de inclusão adotados foram ter 60 anos ou mais e terem respondido à questão sobre autopercepção auditiva. Para fins estatísticos foi realizado o teste Qui-quadrado e regressão logística para avaliar as correlações entre as variáveis. Resultados: Foram excluídos 139 idosos sem resposta à autopercepção auditiva e nove por autorreferirem surdez (7.167 participantes). A frequência de queixa de perda auditiva foi de 28% (2011) dos idosos, apresentou diferença entre gêneros, etnia, renda, participação social. A média de idade dos idosos sem queixa auditiva foi de 69,44 (± 6,91) e com queixa 72,8 (± 7,75) anos. Os idosos sem queixa auditiva apresentaram 5,10 (± 3,78) anos de estudo comparados com 4,48 (± 3,49) anos dos com queixa. A regressão logística múltipla observou que foram fatores protetores para a queixa auditiva maior escolaridade, contribuir na renda familiar e ter recebido atendimento de saúde nos últimos seis meses. Fatores de risco para a queixa auditiva foram idade mais avançada, sexo masculino, apresentar dificuldade de sair de casa e realizar atividades sociais. Conclusões Na população idosa do Rio Grande do Sul a prevalência de queixa auditiva atingiu 28%. A queixa está mais presente em idosos homens, sem participação na renda familiar, não receberam atendimento de saúde, tinham atividade social e comunitária, com menor escolaridade e maior idade.

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Preoperative vestibular assessment protocol of cochlear implant surgery: an analytical descriptive study

Abstract Introduction: Cochlear implants are undeniably an effective method for the recovery of hearing function in patients with hearing loss. Objective: To describe the preoperative vestibular assessment protocol in subjects who will be submitted to cochlear implants. Methods: Our institutional protocol provides the vestibular diagnosis through six simple tests: Romberg and Fukuda tests, assessment for spontaneous nystagmus, Head Impulse Test, evaluation for Head Shaking Nystagmus and caloric test. Results: 21 patients were evaluated with a mean age of 42.75 ± 14.38 years. Only 28% of the sample had all normal test results. The presence of asymmetric vestibular information was documented through the caloric test in 32% of the sample and spontaneous nystagmus was an important clue for the diagnosis. Bilateral vestibular areflexia was present in four subjects, unilateral arreflexia in three and bilateral hyporeflexia in two. The Head Impulse Test was a significant indicator for the diagnosis of areflexia in the tested ear (p = 0.0001). The sensitized Romberg test using a foam pad was able to diagnose severe vestibular function impairment (p = 0.003). Conclusion: The six clinical tests were able to identify the presence or absence of vestibular function and function asymmetry between the ears of the same individual.

Resumo Introdução: Os implantes cocleares (IC) são indiscutivelmente um método eficaz de recuperação da função auditiva de pacientes surdos. Objetivo: Descrever o protocolo de avaliação vestibular pré-operatória em sujeitos que serão submetidos ao IC. Método: Nosso protocolo institucional prevê o diagnóstico vestibular por meio de seis testes simples: testes de Romberg e Fukuda, nistagmo espontâneo, Head Impulse Test, Head Shaking Nistagmus, prova calórica. Resultados: Foram avaliados 21 pacientes com média de 42,75 ± 14,38 anos. Apenas 28% da amostra apresentaram todos os testes normais. A presença de informação vestibular assimétrica foi documentada pela prova calórica em 32% da amostra e o nistagmo espontâneo mostrou-se pista importante para seu diagnóstico. A arreflexia vestibular bilateral foi diagnosticada em quatro sujeitos; arreflexia unilateral em três e hiporreflexia bilateral em dois. O Head Impulse Test mostrou-se indicador significante (p = 0,0001) para diagnosticar arreflexia da orelha testada. O teste de Romberg sensibilizado em almofada foi capaz de diagnosticar os comprometimentos severos da função vestibular (p = 0,003). Conclusão: Os seis testes clínicos foram capazes de identificar a presença ou não de função vestibular e assimetria da função entre as orelhas de um mesmo indivíduo.

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Treatment of large persistent tracheoesophageal peristomal fistulas using silicon rings

Abstract Introduction: Tracheoesophageal peristomal fistulae can often be solved by reducing the size of the fistula or replacing the prosthesis; however, even with conservative techniques, leakage around the fistula may continue in total laryngectomy patients. Also, several techniques have been developed to overcome this problem, including injections around the fistula, fistula closure with local flaps, myofascial flaps, or free flaps and fistula closure using a septal perforation silicon button. Objective: To present the results of the application of silicon ring expanding the voice prosthesis in patients with large and persistent peri-prosthetic fistula. Methods: A voice prosthesis was fitted to 42 patients after total laryngectomy. Leakage was detected around the prosthesis in 18 of these 42 patients. Four patients demonstrated improvement with conservative methods. Eight of 18 patients who couldn't be cured with conservative methods were treated by using primary suture closure and 4 patients were treated with local flaps. As silicon ring was applied as a primary treatment in the 2 remaining patients and also, applied to 2 patients who had recurrence after suture repair and to 2 patients who had recurrence after local flap implementation. Silicon rings were used in a total of 6 patients due to the secondary trachea-esophageal fistula. Patients were treated with provox-1 initially and later with provox-2. At the time of leakage around the fistula, 6 patients had provox-2. Results: Fistulae were treated successfully in 6 patients, and effective speech of patients was preserved. Patients experienced no adaptation problem. Prosthesis changing time was not different between silicon rings expanded and normal prosthesis applied patients. Silicon ring combined voice prosthesis was used 26 times; there was no recurrence in fistula complication during 29 ± 6 months follow up. Conclusion: Silicon rings for modified expanded voice prosthesis seems to be an effective treatment for persistent peri-prosthetic leakage, for both, fistula closure and preserving the patients speech.

Resumo Introdução: Fístulas traqueoesofágicas persistentes podem ser resolvidas através da redução do tamanho da fístula ou substituição da prótese; no entanto, mesmo com técnicas conservadoras, o pertuito em torno da fístula pode continuar em pacientes com laringectomia total. Além disso, várias técnicas têm sido desenvolvidas para superar esse problema, inclusive injeções ao redor da fístula, fechamento da fístula com retalhos locais, retalhos miofasciais ou retalhos livres e fechamento da fístula com um botão septal de silicone. Objetivo: Apresentar os resultados da aplicação de anel de silicone para expansão da prótese vocal em pacientes com grandes fístulas periprotéticas persistentes. Método: Prótese vocal foi colocada em 42 pacientes após laringectomia total, e fístula foi detectada ao redor da prótese em 18 desses 42 pacientes. Quatro pacientes obtiveram melhora com métodos conservadores. Oito dos 18 pacientes que não obtiveram sucesso com métodos conservadores foram tratados usando sutura primária e quatro pacientes foram tratados com retalhos locais. Um anel de silicone foi aplicado inicialmente nos dois pacientes restantes e, também, aplicado a dois pacientes que tiveram recorrência após a técnica de sutura e a dois pacientes que tiveram recorrência após a utilização de retalho local. No total, seis pacientes receberam anéis de silicone em decorrência da fístula traqueoesofágica secundária. Os pacientes haviam sido tratados com provox-1 inicialmente e posteriormente com provox-2. No momento da detecção da fístula em torno do estoma, seis pacientes haviam recebido provox-2. Resultados: A fístula foi tratada com sucesso em seis pacientes. Além disso, após o tratamento a fala foi mantida de forma eficaz. Não houve problema de adaptação. O tempo de troca da prótese expandida com os anéis de silicone não foi diferente do tempo que se leva para a colocação da prótese normal. O anel de silicone combinado com a prótese vocal foi usado 26 vezes em pacientes na época da troca de prótese e não houve recorrência da fístula durante os 29 ± 6 meses de acompanhamento. Conclusão: Os resultados sugerem que em casos de grandes fístulas peri-prostéticas persistentes, anéis expandidos de silicone e prótese vocal modificada são eficazes tanto para o fechamento da fístula como para a manutenção da fala do paciente.

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The effect of melatonin and vitamin C treatment on the experimentally induced tympanosclerosis: study in rats

Abstract Introduction: The ethiopathogenesis of tympanosclerosis has not been completely under- stood yet. Recent studies have shown that free oxygen radicals are important in the formation of tympanosclerosis. Melatonin and Vitamin C are known to be a powerful antioxidant, interacts directly with Reactive Oxygen Species and controls free radical-mediated tissue damage. Objective: To demonstrate the possible preventative effects of melatonin and Vitamin C on tympanosclerosis in rats by using histopathology and determination of total antioxidant status total antioxidant status. Methods: Standard myringotomy and standard injury were performed in the middle ear of 24 rats. The animals were divided into three groups: Group 1 received melatonin, Group 2 received vitamin C, and Group 3 received saline solution. Results: The mean values of total antioxidant status were similar in the all study groups before the treatment period. The mean values of total antioxidant status were significantly higher in the melatonin and vitamin C groups compared to control group but vitamin C with melatonin groups were similar after the treatment period (p < 0.001). Minimum and maximum wall thicknesses were lower in the melatonin and vitamin C groups compared to the control group but the differences were insignificant. Conclusion: Melatonin increases total antioxidant status level and might have some effect on tympanosclerosis that develops after myringotomy.

Resumo Introdução: A etiopatogênese da timpanoesclerose (TE) não foi ainda totalmente esclarecida. Estudos recentes têm demonstrado que os radicais livres de oxigênio são importantes na formação de TE. Melatonina e vitamina C são conhecidas por serem poderosos antioxidantes, interagir diretamente com espécies reativas de oxigênio (ROS) e controlar danos em tecidos mediados por radicais livres. Objetivo: Demonstrar os possíveis efeitos preventivos da melatonina e da vitamina C na TE em ratos com histopatologia e determinação da capacidade antioxidante total (CAT). Método: Miringotomias padronizadas foram feitas na orelha média de 24 ratos. Os animais foram divididos em três grupos: o Grupo 1 recebeu melatonina, o Grupo 2 vitamina C e o grupo 3 solução salina. Resultados: Os valores médios de CAT foram semelhantes em todos os grupos de estudo antes do período de tratamento. Os valores médios de CAT foram significativamente maiores nos grupos que receberam melatonina e vitamina C em comparação com o grupo de controle, mas os grupos vitamina C e melatonina foram semelhantes após o período de tratamento (p < 0,001). As espessuras mínimas e máximas de parede foram menores nos grupos melatonina e vitamina C, em comparação com o grupo controle, mas as diferenças não foram significativas. Conclusão: A melatonina aumenta os níveis de CAT e pode ter algum efeito sobre a TE que se desenvolve após a miringotomia.

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Αρχειοθήκη ιστολογίου

Πέμπτη 19 Οκτωβρίου 2017

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Abstract

Background

Methods

Results

Conclusion

Abstract

Background

Methods

Results

Conclusion

Abstract

Background

Methods

Results

Conclusions

Abstract

Background

Methods

Results

Conclusion

Abstract

Background

Methods

Results

Conclusions

Abstract

Background

Methods

Results

Conclusion

Abstract

Background

Methods

Results

Conclusions

Abstract

Background

Methods

Results

Conclusions

Abstract

Background

Methods

Results

Conclusions

Teaser

Abstract

Abstract

Abstract