Surgical Correction of Nasal Obstruction and Its Effect on Eustachian Tube Dysfunction Symptoms.

OBJECTIVES: To investigate how eustachian tube dysfunction symptoms change following surgical treatment of nonsinusitis-related nasal obstruction. STUDY DESIGN: Retrospective chart review. SETTING: Single academic center. METHODS: We assessed patients who underwent septoplasty, turbinate reduction, or both for nasal obstruction. Chronic sinusitis patients were excluded. Eustachian tube dysfunction (ETD) symptoms were studied using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7), collected preoperatively and postoperatively (1 week, 1 month, 3 months, 6 months postop). Patients with preoperative ETDQ-7 > 14.5 were considered to have clinically significant symptoms. Sinonasal outcomes test scores were also assessed. Pre- and postoperative ETDQ-7 scores were compared using t test. Multivariate linear regression analysis identified factors associated with ETDQ-7 change. RESULTS: We analyzed 259 patients. Preoperatively, 37.5% of patients with nasal obstruction had clinically significant ETD symptoms. These patients exhibited significant improvement in ETDQ-7 at all postoperative timepoints from 23.3 ± 7.6 at baseline to 19.1 ± 9.1 at 1 week, 16.5 ± 8.0 at 1 month, 16.2 ± 7.8 at 3 months, and 16.7 ± 10.4 at 6 months (all P < .01). In patients without baseline ETD symptoms, (baseline ETDQ-7: 9.1 ± 2.3) ETDQ-7 scores did not change significantly at postoperative timepoints, except for an acute worsening at 1 week postoperatively (10.7 ± 5.1, P < .001). Regression analysis showed that higher preoperative ETDQ-7 score (ß = -0.84, 95% confidence interval [CI]: -1.10 to -0.59) and postoperative antihistamine spray usage (ß = -8.70, 95% CI: -14.20 to -3.20) were associated with ETDQ-7 improvement, while comorbid GERD (ß = 7.50, 95% CI: 3.42-11.58) and asthma (ß = 5.62, 95% CI: 0.80-10.45) were negatively associated with improvement. CONCLUSION: Surgical correction of nasal obstruction may improve ETD symptoms.

Social determinants of health Z-codes and postoperative outcomes after colorectal surgery: A national population-based study.

BACKGROUND: We sought to evaluate the impact of social determinants of health (SDOH) on postoperative outcomes following colorectal surgery. METHODS: This retrospective cohort study used PearlDiver-Mariner, an all-payer insurance claims database. Patients who underwent colectomy or proctectomy between 2010 and 2020 were included. SDOH were identified using International Classification of Diseases diagnosis codes. Outcomes were compared using multivariable regression models. RESULTS: The 30-day postoperative complication rate among 333,387 patients (mean age, 59 years; 58% female) was 27%. Approximately 5% of patients reported at least one SDOH at baseline. SDOH were not associated with length of stay but were associated with higher odds of 30-day postoperative complications (OR:1.16, 95% CI:1.12-1.20), including urinary tract infection (OR:1.27, 95% CI:1.20-1.35) anastomotic leak (OR:1.22, 95% CI:1.16-1.28), pneumonia (OR:1.19, 95% CI:1.11-1.27), deep vein thrombosis (OR:1.13, 95% CI:1.02-1.23), sepsis (OR:1.12, 95% CI:1.07-1.18), disruption of wound (OR:1.12, 95% CI:1.03-1.21), and acute kidney injury (OR:1.04, 95% CI:0.99-1.10). CONCLUSIONS: SDOH Z-codes were associated with worse postoperative complications following colorectal surgery and may help target high-risk patients.

Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease.

PURPOSE: To characterize the frequency, severity, and resolution of hearing dysfunction in patients treated with teprotumumab for thyroid eye disease (TED). DESIGN: Prospective observational case series. METHODS: Ophthalmic examination and adverse event assessment, including otologic symptoms, were performed at baseline, after infusions 2, 4, and 8, and at 6-month follow-up in consecutive patients who received at least 4 teprotumumab infusions. Laboratory test results were collected at baseline and during treatment. Audiometry, patulous eustachian tube (PET) testing, and otolaryngology evaluation were obtained for patients with new or worsening otologic symptoms, with a subset obtaining baseline and posttreatment testing. RESULTS: Twenty-seven patients were analyzed (24 females, 3 males, average 56.3 years old). Twenty-two patients (81.5%) developed new subjective otologic symptoms, after a mean of 3.8 infusions (SD 1.8). At 39.2-week average follow-up after the last infusion, most patients with tinnitus (100%), ear plugging/fullness (90.9%), and autophony (83.3%) experienced symptom resolution, whereas only 45.5% (5 of 11) of patients with subjective hearing loss/decreased word comprehension experienced resolution. Six patients underwent baseline and posttreatment audiometry, 5 of whom developed teprotumumab-related sensorineural hearing loss (SNHL) and 1 patient also developed PET. Three of the 5 patients with teprotumumab-related SNHL had persistent subjective hearing loss at last follow-up. A prior history of hearing loss was discovered as a risk factor for teprotumumab-related SNHL (P = .008). CONCLUSIONS: Hearing loss is a concerning adverse event of teprotumumab, and its mechanism and reversibility should be further studied. Until risk factors for hearing loss are better understood, we recommend baseline audiometry with PET testing and repeat testing if new otologic symptoms develop. Screening, monitoring, and prevention guidelines are needed.

Flexible Bronchoscopy Simulation as a Tool to Improve Surgical Skills in Otolaryngology Residency.

OBJECTIVE: To evaluate the benefits of simulation to teach flexible bronchoscopy. STUDY DESIGN: A prospective cohort study to assess the bronchoscopic skills of residents in an otolaryngology training program using a commercially available bronchoscopy simulator. SETTING: Tertiary care otolaryngology residency program. METHODS: Thirty-two otolaryngology residents and 4 expert faculty across 2 academic institutions were assessed on 3 flexible bronchoscopy tasks: diagnostic bronchoscopy, foreign body removal, and tracheal lesion biopsy. Performance was evaluated with a modified version of the validated Bronchoscopy Skills and Tasks Assessment Tool. At 1 of the 2 academic institutions, an additional tool was implemented to evaluate the simulator. RESULTS: There was a correlation between postgraduate training year and time taken to complete tasks, including bronchoscopy, foreign body extraction, and passing through the glottis (P < .001, P = .04, and P < .01, respectively). There was a significant difference between residents and faculty laryngologists for a range of skills and tasks, including percentage of time in middle lumen, contact with bronchial walls, inadvertent esophagus entry, and biopsy of healthy tissue (P < .001, P = .003, P < .001, and P < .001). Additionally, increasing postgraduate level was correlated with a higher percentage of time in the center of the lumen and reduced time to task completion (P = .05 and P < .001). Of 32 residents, 20 evaluated the simulator on its realism, with an average score of 4.1 of 5. CONCLUSION: The commercially available flexible bronchoscopy simulator provides a valid assessment of bronchoscopic skill and is a useful tool for practicing bronchoscopy in a safe, controlled environment. LEVEL OF EVIDENCE: Individual cohort study.

Nephrobiliary fistula resulting from a gunshot wound in a young healthy male: A case report.

Biliary fistulas are most commonly caused by cholelithiasis. Other causes include malignancies and peptic ulcer disease. A biliary fistula caused by a penetrating trauma is a rare entity, and a post-traumatic biliary fistula to the renal collecting system is extremely uncommon. We present an extremely rare case of a post-traumatic nephrobiliary fistula incurred after penetrating trauma that was successfully treated with endoscopic retrograde cholangiopancreatography (ERCP), biliary stents, and percutaneous drainage.

Development of an Algorithm to Identify Cases of Nonalcoholic Steatohepatitis Cirrhosis in the Electronic Health Record.

BACKGROUND AND AIMS: Current genetic research of nonalcoholic steatohepatitis (NASH) cirrhosis is limited by our ability to accurately identify cases on a large scale. Our objective was to develop and validate an electronic health record (EHR) algorithm to accurately identify cases of NASH cirrhosis in the EHR. METHODS: We used Clinical Query 2, a search tool at Beth Israel Deaconess Medical Center, to create a pool of potential NASH cirrhosis cases (n = 5415). We created a training set of 300 randomly selected patients for chart review to confirm cases of NASH cirrhosis. Test characteristics of different algorithms, consisting of diagnosis codes, laboratory values, anthropomorphic measurements, and medication records, were calculated. The algorithms with the highest positive predictive value (PPV) and the highest F score with a PPV ≥ 80% were selected for internal validation using a separate random set of 100 patients from the potential NASH cirrhosis pool. These were then externally validated in another random set of 100 individuals using the research patient data registry tool at Massachusetts General Hospital. RESULTS: The algorithm with the highest PPV of 100% on internal validation and 92% on external validation consisted of ≥ 3 counts of "cirrhosis, no mention of alcohol" (571.5, K74.6) and ≥ 3 counts of "nonalcoholic fatty liver" (571.8-571.9, K75.81, K76.0) codes in the absence of any diagnosis codes for other common causes of chronic liver disease. CONCLUSIONS: We developed and validated an EHR algorithm using diagnosis codes that accurately identifies patients with NASH cirrhosis.

Vedolizumab Serum Trough Concentrations and Response to Dose Escalation in Inflammatory Bowel Disease.

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 µg/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration <7.4 µg/mL responded versus 52% of those with a vedolizumab trough concentration ≥7.4 µg/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration <7.4 µg/mL was 3.7 (95% CI, 1.1-13; p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

Primary small cell carcinoma of the adrenal gland: Case presentation of a rare extrapulmonary small cell carcinoma.

Small cell carcinoma (SCC) is an aggressive histologic subtype of neuroendocrine tumor and is most commonly of bronchogenic origin. However, it can present in an extrapulmonary fashion. Primary extrapulmonary small cell carcinoma (EPSCC) is a rare disease entity, especially within the genitourinary system and furthermore of the adrenal gland. There are scarce case reports that describe management of primary adrenal SCC. We present a case of localized primary adrenal SCC diagnosed on adrenal mass biopsy and successfully treated via neoadjuvant chemotherapy and extirpative surgery.

Should a Drain Be Routinely Required After Transperitoneal Robotic Partial Nephrectomy?

Introduction: Closed drains have traditionally been placed after partial nephrectomy because of risks of bleeding and urine leak. We sought to study the safety of a nonroutine drain (NRD) approach after transperitoneal robotic partial nephrectomy (RPN). Patients and Methods: From a multi-institutional database, we have analyzed the data of 904 patients who underwent RPN. Five hundred forty-six (60.40%) patients underwent RPN by a surgeon who routinely placed drains. Three hundred fifty-eight (39.60%) patients underwent RPN by a surgeon who did not routinely placed drains. Perioperative outcomes, length of stay (LOS), and readmission rates were compared between the two groups. Baseline characteristics, perioperative, and postoperative outcomes were compared using Mann-Whitney U test, chi-square test, and Fisher's exact test. Results: Patients in the NRD group were more likely to have higher body mass index (30.10 kg/m2vs 28.07 kg/m2; P < 0.001), higher tumor size (3.0 cm vs 2.5 cm; P = 0.001), and higher renal score (8 vs 7; P < 0.001). Rate of transfusion (0.00% NRD vs 0.56% RD; P = 0.157) and overall complication (7.33% NRD vs 7.82% RD; P = 0.782) were comparable. Median hospital stay is 1 day for both groups. Readmission rate was also similar (0.55% NRD vs 1.40% RD; P = 0.279). In a multivariable analysis, NRD approach was associated with shorter length of hospital stay (incidence rate ratio [IRR] - 0.72, P < 0.001). Conclusion: An NRD approach for RPN yielded a decreased LOS and similar perioperative outcomes. Placement of surgical drains should be based on individual circumstances, and not required on a routine basis.

The Effect of Endoscopic Sinus Surgery on Eustachian Tube Dysfunction Symptoms.

OBJECTIVE: We assessed how eustachian tube dysfunction (ETD) changed with endoscopic sinus surgery (ESS) and identified factors associated with improvement. STUDY DESIGN: Retrospective chart review. SETTING: Academic center. SUBJECTS AND METHODS: Patients undergoing ESS for chronic rhinosinusitis with and without nasal polyposis (CRSwNP, CRSsNP) or recurrent acute rhinosinusitis (RARS) completed the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7) preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, and 6 months. Included in analyses were demographics, comorbidities, Sinonasal Outcome Test 22 (SNOT-22), radiographic score, endoscopy score, procedure, and medication use. Regression analysis identified factors associated with improvement, defined as ΔETDQ-7 >3.5. RESULTS: In total, 302 patients were studied. ETD prevalence was 68% in CRSsNP, 48% in CRSwNP, and 88% in RARS. Patients with ETD had a mean baseline ETDQ-7 of 25.8 ± 8.0 and improved postoperatively at 2 weeks (19.9 ± 8.1, P < .001), 6 weeks (17.8 ± 9.3, P < .001), 3 months (16.8 ± 8.5, P < .001), and 6 months (16.4 ± 7.9, P < .001). At 6 months, ETD improved in 89% of patients with CRSsNP, 68% with CRSwNP, and 78% with RARS. On multivariate analysis, ETD improvement was associated with higher preoperative ETDQ-7 score (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.04-1.22; P = .030), higher preoperative SNOT-22 score (aOR, 1.02; 95% CI, 1.02-1.08; P = .001), higher preoperative SNOT-22 ear subscore (aOR, 1.27; 95% CI, 1.02-1.65; P = .034), posterior ethmoidectomy (aOR, 1.59; 95% CI, 1.22-4.92; P = .025), and postoperative corticosteroid spray use (aOR, 1.57; 95% CI, 1.17-1.66; P = .008). CONCLUSION: ETD symptoms often improve following ESS. Factors associated with improvement include higher preoperative disease burden, posterior ethmoidectomy, and postoperative corticosteroid spray. LEVEL OF EVIDENCE: 4.

Novel HDAC11 inhibitors suppress lung adenocarcinoma stem cell self-renewal and overcome drug resistance by suppressing Sox2.

Non-small cell lung cancer (NSCLC) is known to have poor patient outcomes due to development of resistance to chemotherapy agents and the EGFR inhibitors, which results in recurrence of highly aggressive lung tumors. Even with recent success in immunotherapy using the checkpoint inhibitors, additional investigations are essential to identify novel therapeutic strategies for efficacious treatment for NSCLC. Our finding that high levels of histone deacetylase 11 (HDAC11) in human lung tumor tissues correlate with poor patient outcome and that depletion or inhibition of HDAC11 not only significantly reduces self-renewal of cancer stem cells (CSCs) from NSCLC but also decreases Sox2 expression that is essential for maintenance of CSCs, indicates that HDAC11 is a potential target to combat NSCLC. We find that HDAC11 suppresses Sox2 expression through the mediation of Gli1, the Hedgehog pathway transcription factor. In addition, we have used highly selective HDAC11 inhibitors that not only target stemness and adherence independent growth of lung cancer cells but these inhibitors could also efficiently ablate the growth of drug-insensitive stem-like cells as well as therapy resistant lung cancer cells. These inhibitors were found to be efficacious even in presence of cancer associated fibroblasts which have been shown to contribute in therapy resistance. Our study presents a novel role of HDAC11 in lung adenocarcinoma progression and the potential use of highly selective inhibitors of HDAC11 in combating lung cancers.

HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms.

Protein acetylation is an important contributor to cancer initiation. Histone deacetylase 6 (HDAC6) controls JAK2 translation and protein stability and has been implicated in JAK2-driven diseases best exemplified by myeloproliferative neoplasms (MPNs). By using novel classes of highly selective HDAC inhibitors and genetically deficient mouse models, we discovered that HDAC11 rather than HDAC6 is necessary for the proliferation and survival of oncogenic JAK2-driven MPN cells and patient samples. Notably, HDAC11 is variably expressed in primitive stem cells and is expressed largely upon lineage commitment. Although Hdac11is dispensable for normal homeostatic hematopoietic stem and progenitor cell differentiation based on chimeric bone marrow reconstitution, Hdac11 deficiency significantly reduced the abnormal megakaryocyte population, improved splenic architecture, reduced fibrosis, and increased survival in the MPLW515L-MPN mouse model during primary and secondary transplantation. Therefore, inhibitors of HDAC11 are an attractive therapy for treating patients with MPN. Although JAK2 inhibitor therapy provides substantial clinical benefit in MPN patients, the identification of alternative therapeutic targets is needed to reverse MPN pathogenesis and control malignant hematopoiesis. This study establishes HDAC11 as a unique type of target molecule that has therapeutic potential in MPN.

Increased Posttransplant Mortality for Autoimmune Hepatitis Compared With Other Autoimmune Liver Diseases.

GOALS: We sought to compare posttransplant outcomes between autoimmune liver disease. BACKGROUND: Autoimmune liver diseases, namely primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) generally have favorable posttransplant outcomes. PSC is known to require more retransplantation compared with PBC, however, comparisons to AIH are lacking. We sought to compare graft survival and the need for retransplant in AIH compared with other autoimmune liver disease. STUDY: We compared posttransplant graft survival among the 3 entities using Cox regression and competing for risk analyses using the United Network for Organ Sharing (UNOS) database. RESULTS: We found AIH is associated with significantly decreased graft survival compared with PBC [hazard ratio: 0.86; 95% confidence interval (CI): 0.77-0.96] and PSC (hazard ratio: 0.89; 95% CI: 0.8-0.99) after controlling for potential confounders. This is mainly driven by posttransplant death. On competing for risk analysis, AIH was associated with higher risk of death compared with PBC [subdistribution hazard ratio (SHR): 0.79; 95% CI: 0.7-0.89] and PSC (SHR: 0.72; 95% CI: 0.64-0.82) and lower risk of retransplant compared with PSC (SHR: 1.48; 95% CI: 1.19-1.8). CONCLUSION: As prior studies have shown the similar risk of disease recurrence in AIH and PSC, our study indicates at least part of the increased posttransplant mortality in AIH may be due lower retransplantation rate in this population.

Treatment of Fatigue in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Fatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed mechanisms of PBC-associated fatigue. We sought to summarize and perform a meta-analysis to determine the efficacy of these interventions. METHODS: A comprehensive database search was conducted from inception through March 27, 2018. The primary outcome was proportion of fatigued patients or reduction in degree of fatigue. Adverse events were a secondary outcome. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same class. RESULTS: We identified 16 studies evaluating ursodeoxycholic acid (UDCA) (7), liver transplantation (2), serotonin reuptake inhibitors (2), colchicine (1), methotrexate (1), cyclosporine (1), modafinil (1), and obeticholic acid (1). On meta-analysis, UDCA was not associated with a reduction in risk of fatigue (RR = 0.86, 95% CI 0.69-1.08, p = 0.19, I2 = 56.2%). While liver transplantation did reduce degree of fatigue (SMD - 0.57, 95% CI - 0.89 to - 0.24, p = 0.001, I2 = 67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed. CONCLUSIONS: While there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue. Further research into the underlying pathophysiology may help guide future trials.

Patient preferences regarding the communication of biopsy results in the general otolaryngology clinic.

OBJECTIVES: To determine the preferred methods of communicating biopsy results for patients in our comprehensive otolaryngology clinic, and to examine factors associated with preferring remote vs. in-person communication of results. STUDY DESIGN: Cross-sectional study. SETTING: Academic comprehensive otolaryngology clinic. SUBJECTS AND METHODS: A survey instrument was administered to 107 consecutive adult otolaryngology patients undergoing head and neck fine needle aspiration biopsy from March 1, 2017 to April 30, 2018 assessing their health literacy using the Brief Health Literacy Score and their preferred method of notification of biopsy results (in-person vs. remote). RESULTS: 69% of patients preferred remote notification of their biopsy results (either by telephone or via an online portal). 54% of patients prioritized clear explanation of the results as the most important factor when communicating a malignant result. Adequate health literacy was associated with lower odds of preferring in-person notification (adjusted odds ratio 0.11, 95% CI 0.03 to 0.39). Patients who prioritized clear explanation of the results were more likely to prefer in-person notification (adjusted OR 4.13, 95% CI 1.31 to 14.88). CONCLUSIONS: A significant proportion of patients in our comprehensive otolaryngology clinic undergoing fine needle aspiration biopsy preferred remote communication of their biopsy results. Patients most valued clear explanations from the provider and prompt receipt of the result when communicating malignant results. This highlights the need for individualized results communication plans, for patients undergoing biopsy.

Discovery of novel N-hydroxy-2-arylisoindoline-4-carboxamides as potent and selective inhibitors of HDAC11.

N-Hydroxy-2-arylisoindoline-4-carboxamides are potent and selective inhibitors of HDAC11. The discovery, synthesis, and structure activity relationships of this novel series of inhibitors are reported. An advanced analog (FT895) displays promising cellular activity and pharmacokinetic properties that make it a useful tool to study the biology of HDAC11 and its potential use as a therapeutic target for oncology and inflammation indications.

Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma.

PURPOSE: In this study, we compare an abbreviated screening MRI protocol (aMRI), utilizing only dynamic contrast-enhanced images, to a conventional liver MRI (cMRI) for the characterization of observations in at-risk patients. MATERIALS AND METHODS: 164 consecutive HCC screening MRIs were retrospectively analyzed. Two sets of de-identified image sets were created: one with all acquired sequences including T2- and diffusion-weighted sequences (cMRI), and one with only T1-weighted precontrast and dynamic post-contrast images utilizing an extracellular gadolinium contrast agent (aMRI). Three readers assigned a LI-RADS score based on the lesion with the highest LI-RADS category using the aMRI and cMRI datasets during separate reads. RESULTS: There was no change between the aMRI and cMRI LI-RADS categorization in 93%, 96%, and 96% of cases for readers 1, 2, and 3, respectively. In the majority of the discrepant cases, the score increased from LI-RADS 3 to LI-RADS 4 due to the presence of ancillary features on T2 and DWI. Kappa values for interobserver variability demonstrated fair-to-moderate LI-RADS agreement among the 3 readers. CONCLUSION: There was strong agreement between the abbreviated T1-only MRI protocol and a full liver MRI, with only 5% of cases changing LI-RADS categorization due to the inclusion of T2 and DWI. The estimated time to run this abbreviated MRI is approximately 7-10 min, possibly allowing for a more cost-effective screening MRI than our cMRIs.