Citations

Abstract Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

BACKGROUND Current consensus guidelines have discouraged the use of sub-0.5-cm (in situ) and sub-1-cm (invasive) margins when performing Mohs micrographic surgery (Mohs) for melanoma, with minimal evidence to guide this recommendation. OBJECTIVE To compare melanoma local recurrence rates after Mohs based on initial margin size. MATERIALS AND METHODS A systematic review and meta-analysis was conducted with search terms including Mohs micrographic surgery, surgical margin, recurrent disease, and melanoma. RESULTS Forty-three studies were included. The 5- to 10-mm margin category had a statistically significant lower local recurrence compared with 1- to 5-mm and 5-mm categories. Recurrence for 1- to 5-mm, 5-mm, 5- to 10-mm, and 10-mm categories were 2.3% (CI 0.8–3.5, p < .001), 1.4% (CI 0.6–2.2, p < .001), 0.3% (CI 0.2–0.5, p < .001), and 6.1% (CI -6.7 - 18.8, p = .349), respectively. Number of stages for 1 to 5, 5, 5 to 10, and 10-mm categories were 1.8, 1.8, 1.6, and 1.6, respectively. There was no statistically significant difference between the groups (p = .694). CONCLUSION Five- to 10-mm margins were associated with the lowest local recurrence rates. A 5- to 10-mm initial margin should be considered where other factors (tumor characteristics, anatomical or functional considerations) allow.

Abstract Background Computed tomography enterography (CTE) is frequently used to assess stricturing Crohn’s disease (CD). However, the reliability of CTE items used for assessment has not been established and there is no validated radiologic stricture severity index. Methods We conducted a retrospective study of 43 patients with symptomatic, terminal ileal stricturing CD. Four radiologists assessed a comprehensive list of pre-defined radiologic items potentially associated with stricture severity in 48 CTE scans in two separate rounds in random order. Reliability was quantified using the intraclass correlation coefficient (ICC). Items with at least moderate (ICC≥0.41) inter-rater reliability that were correlated with a visual analogue scale of overall stricture severity were candidate items for the development of a CTE stricture index. Results Inter-rater reliability was almost perfect for assessment of luminal diameter of pre-stenotic dilation (ICC 0.817 [95% confidence interval 0.703, 0.878]), substantial for stricture length (ICC 0.628 [0.419, 0.797]), and moderate for stricture wall thickness (0.482 [0.330, 0.601]). Intra-rater reliability was almost perfect (ICC ≥ 0.850) for all three items. A stricture severity index was derived and was well calibrated (optimism-adjusted calibration slope = 1.009), with scores calculated as the sum of stricture length (cm) + luminal diameter of pre-stenotic dilation (mm) + 5 x stricture wall thickness (mm). Conclusion Stricture length, prestenotic dilation, and stricture wall thickness can be reliably assessed, and are component items for a novel CTE stricture index (CTE-SI) of stricture severity for CD-related terminal ileal strictures. Additional external index validation for clinical and research contexts is required.

AbstractObjectivePrevious studies have suggested that patients with aspirin‐exacerbated respiratory disease (AERD) have a high likelihood of alcohol intolerance. The purpose of this systematic review is to identify if there is sufficient evidence to confirm this correlation and the impact of medical therapy on subsequent alcohol tolerance.Data SourcesPubMed, EMBASE, SCOPUS, EBSCO, Google Scholar, Cochrane Library, and Grey literature. We also performed snowballing on the identified observational studies (OS) for additional data.Review MethodsA systematic review was conducted from 1968 to 2022 to identify those studies describing AERD symptomatology triggered by alcohol intake. The primary outcome was to analyze the current literature for the association between alcohol intolerance and AERD symptoms. The secondary outcome looked for improvement in alcohol tolerance after aspirin desensitization or biological therapy.ResultsA total of 775 studies were identified and 40 abstracts were evaluated. From these, 5 studies met the inclusion criteria. Of the 5 manuscripts, there was 1 case‐control, 2 cohort, and 2 cross‐sectional studies. A total of 522 participants with AERD and a history of alcohol consumption were included, with 52.8% reporting at least 1 sinopulmonary exacerbation after alcohol intake. One of 3 studies noted improvement in alcohol tolerance after medical therapy with aspirin desensitization.ConclusionThe current literature suggests that patients with AERD have a high risk of alcohol intolerance. Additionally, aspirin desensitization may improve alcohol tolerance in this patient population.

AbstractObjectivesTo create an otolaryngology‐specific needs assessment tool for short‐term global surgical trips and to describe our findings from its implementation.MethodsSurveys 1 and 2 were developed based on a literature review and disseminated to Low‐Middle Income (LMIC) hosting institutions in Kenya and Ethiopia and to High‐Income surgical trip participants (HIC), respectively. Respondents were otolaryngologists identified online, through professional organizations, and by word‐of‐mouth, who had participated in a surgical trip of <4 weeks.ResultsHIC and LMIC respondents shared similar goals of expanding host surgical skills through education and training while building sustainable partnerships. Discrepancies were identified between LMIC desired surgical skills and supply needs and HIC current practices. Microvascular reconstruction (17.6%), advanced otologic surgery (17.6%), and FESS (14.7%) were most desired skills and high‐demand equipment needs were FESS sets (89%), endoscopes (78%), and surgical drills (56%). Frequently taught techniques included advanced otologic surgery (36.6%), congenital anomaly surgery (14.6%), and FESS (14.6%) with the largest gap between LMIC‐need and HIC‐offerings being in microvascular reconstruction (17.6% vs. 0%). We also highlight the discrepancy in expectations of responsibility for trip logistics, research, and patient follow‐up.ConclusionWe created and implemented the first otolaryngology‐specific needs assessment tool in the literature. With its implementation in Ethiopia and Kenya, we were able to identify unmet needs as well as attitudes and perceptions of LMIC and HIC participants. This tool may be adapted and utilized to assess specific needs, resources, and goals of both host and visiting teams to facilitate successful global partnerships.Level of EvidenceLevel VI.

AbstractBackgroundDecisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid test‐positive (NAT+) donors must balance risk of donor‐derived transmission events (DDTE) with the scarcity of available organs.MethodsOrgan Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS‐CoV‐2 NAT+ and NAT– donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee.ResultsFrom May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT– donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT– donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30‐day mortality, and 30‐day graft loss were similar for all organ types. No SARS‐CoV‐2 DDTE occurred in this interval.ConclusionsTransplantation of SARS‐CoV‐2 NAT+ donor organs appears safe for short‐term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes. image

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.

Objective: To compare 12-month post-treatment health-related quality of life (HR-QoL) and symptom severity (SS) changes among patients with symptomatic uterine fibroids (SUF) not seeking fertility and undergo a hysterectomy, abdominal myomectomy (AM), or uterine artery embolization (UAE). Materials and Methods: The Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) Registry is a multi-institutional prospective observational cohort study of patients treated for SUF. A subset of 1465 women 31–45 years of age, who underwent either hysterectomy ( n = 741), AM ( n = 446), or UAE ( n = 155) were included in this analysis. Demographics, fibroid history, and symptoms were obtained by baseline questionnaires and at 1 year post-treatment. Results were stratified by all treatments and propensity score weighting to adjust for differences in baseline characteristics. Results: Women undergoing UAE reported the lowest baseline HR-QoL and highest SS scores (mean = 40.6 [standard deviation (SD) = 23.8]; 62.3 [SD = 24.2]) followed by hysterectomy (44.3 [24.3]; 59.8 [SD = 24.1]). At 12 months, women who underwent a hysterectomy experienced the largest change in both HR-QoL (48.7 [26.2]) and SS (51.9 [25.6]) followed by other uterine-sparing treatments. Propensity score weighting revealed all treatments produced substantial improvement, with hysterectomy patients reporting the highest HR-QoL score (92.0 [17.8]) compared with myomectomy (86.7 [17.2]) and UAE (82.6 [21.5]) ( p < 0.0001). Similarly, hysterectomy patients reported the lowest SS scores (8.2 [15.1]) compared with myomectomy (16.5 [15.1]) and UAE (19.6 [17.5]) ( p < 0.0001). Conclusion: All procedures showed improvement in HR-QoL and reduction in SS score at 12 months, hysterectomy showing maximum improvement. Of importance, at 12 months, patients who underwent either a myomectomy or UAE reported comparable symptom relief and HR-QoL. Clinicaltrials.Gov Identifier: NCT02260752.