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INTORDUCTION: The management of musculoskeletal tumours is complex and requires a multi-disciplinary approach. Preoperative embolisation can be often employed to reduce intra-operative blood loss and complication rates from surgery. We report our experience with the safety, technical success and efficacy of pre-operative embolisation in musculoskeletal tumours. MATERIALS AND METHODS: Thirteen consecutive patients who underwent pre-operative embolisation of a musculoskeletal tumour followed by surgical intervention at our institution from May 2012 to January 2016 were enrolled into the study. Patient demographics, tumour characteristics, embolisation techniques and type of surgery were recorded. Technical success of embolisation, amount of blood loss during surgery and transfusion requirements were estimated. RESULTS: There were five female and eight male patients who underwent pre-operative embolisation during the study period. The age ranged between 16 to 68 years, and the median age was 54. Technical success was achieved in all patients. Mean intra-operative blood loss was 1403ml, with a range of 150ml to 6900ml. Eight patients (62%) required intra-operative blood products of packed red blood cells and fresh frozen plasma. No major complications occurred during embolisation. CONCLUSION: Pre-operative trans-arterial embolisation is feasible and safe for a variety of large and hypervascular musculoskeletal tumours. Our small series suggests that preoperative embolisation could contribute to the reduction of the intra-operative and post-operative blood product transfusion. It should be considered as a pre-operative adjunct for major tumour resections with a high risk of bleeding. The use of the haemoglobin gap complemented the assessment of perioperative blood loss.

BackgroundAdenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT.Patients and methodsIn a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i.d. Response was assessed every 8 weeks using RECIST.ResultsOf 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28 : 26, median age 56 years (range 20-82 years), ECOG performance status 0 : 1 : 2 = 24 : 28 : 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as % of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progression-free survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2.ConclusionAlthough there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50% of ACC patients. Dasatinib demonstrated no activity in non-ACC MSGT.

Babesiosis is usually acquired from a tick bite or through a blood transfusion. We report a case of babesiosis in an infant for whom vertical transmission was suggested by evidence of Babesia spp. antibodies in the heel-stick blood sample and confirmed by detection of Babesia spp. DNA in placenta tissue. [ABSTRACT FROM AUTHOR]

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells. [ABSTRACT FROM AUTHOR]

Goals Of Work: We report the first analysis of demographic, socioeconomic, and toxicity data from the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN).Materials and Methods: Eligible patients include newly diagnosed Head and Neck Cancer (HNC) patients, scheduled to receive radiotherapy or drug therapy, > or =18 years of age, and able to provide informed consent. Assessments are completed at baseline, at the completion of therapy, and yearly thereafter. Patient data are entered in the registry electronically and transferred via Secure HTTP protocols.Results: Reported use of supportive care differed by treatment setting. When compared to community sites, patients at academic centers received more supportive interventions: feeding tube (59% vs. 48%; p = 0.001), tracheotomy tube (16% vs. 9%; p = 0.002), opioid analgesics (89% vs. 59%; p < 0.0001), anti-emetics (83% vs. 68%; p < 0.0001), and amifostine (17% vs. 12%; p = 0.02). Reported grades 3-4 mucositis/stomatitis was also higher in patients treated at academic centers (38% vs. 28%; p = 0.001).Conclusion: There was a marked decrease in the documented use of supportive care measures in the community setting. This may be due to (1) lower rates of toxicity requiring less supportive care, (2) less stringent documentation, or (3) less aggressive use of supportive care measures. The documented rate of mucositis was less than expected. This is likely due to inadequate assessment or documentation. Further exploration of these findings is warranted as they may indicate an under appreciation and undertreatment of clinically significant acute tumor and treatment-related toxicities. [ABSTRACT FROM AUTHOR]

Massive rotator cuff tears are a challenge for patients and surgeons. We explored the outcomes of patients with massive rotator cuff tears primarily treated with primary cuff repair augmented with a subacromial balloon spacer. The mean age of the patients was 64.3 years, with 24 (71%) having massive cuff tears and the remaining 29% having large cuff tears. Most patients (61%) exhibited significant fatty atrophy (at least grade 3 Goutallier). At 6 months, patients showed improved Constant score, UCLA score, and Oxford Shoulder Score. Pain scores also significantly decreased. A phase 1 study of postoperative imaging indicated balloon disintegration in 50% of cases at 6 weeks. Augmenting primary cuff repair with a subacromial balloon spacer demonstrates promising short-term outcomes. Our postoperative images suggest that balloon disintegration may occur as early as 6 weeks. We recommend caution in using a balloon spacer as a standalone therapy. [ Orthopedics . 202x;4x(x):xx-xx.].

Background: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab., Methods: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III-IVB p16-negative HNSCC or unfavourable stage I-III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity). Patients were randomly assigned (2:1) by permuted block randomisation (multiples of 6) to intravenous durvalumab 1500 mg starting 2 weeks before radiotherapy then every 4 weeks starting week 2 of radiotherapy (seven cycles) or intravenous cetuximab 400 mg/m 2 1 week before radiotherapy then 250 mg/m 2 weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with ClinicalTrials.gov, NCT03258554, and is closed to enrolment., Findings: Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64-77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9-3·1) for the extended follow-up (data cutoff July 31, 2023; post-hoc analysis), 2-year progression-free survival was 50·6% (95% CI 41·5-59·8) in the durvalumab group versus 63·7% (51·3-76·1) in the cetuximab group (hazard ratio 1·33 [95% CI 0·84-2·12]; p=0·89). Adverse events were similar in both groups. The most common grade 3-4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events (death not otherwise specified, laryngeal oedema, lung infection, and respiratory failure in the durvalumab group and sudden death not otherwise specified in the cetuximab group)., Interpretation: Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin. Further trials are needed to define the standard of care for this population., Funding: US National Cancer Institute and AstraZeneca., Competing Interests: Declaration of interests MJA declares grants or contracts from the National Institutes of Health (NIH; R21 for phase 1 trial DEHART), receipt of equipment, materials, drugs, medical writing, gifts, or other services from Genentech for drug only support for NIH R21. JEB declares clinical trial grants from Aveo, Celldex, CUE, Genentech, and Moderna, and consulting fees from Bluedot Bio and Exelixis. ND declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca. CH declares participation on a medical advisory board for EMD Serono, and a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid as co-chair of the Young Investigators Committee of the Head and Neck Cancer International Group. RCJ declares royalties or license from Elsevier for a textbook authorship. Q-TL declares a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid as Radiation Therapy Oncology group chair for NRG Oncology. LKM declares grants or contracts from AstraZeneca and Merck to their institution, consulting fees from Pfizer, and payment for expert testimony from Arnold & Porter. HSP declares grants or contracts from RefleXion and Merck to their institution, consulting fees from AstraZeneca and RefleXion, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol Myers Squibb and G1 Therapeutics, and participation on a data safety monitoring board or advisory board at AstraZeneca and Galera. SP declares grants or contracts from Merck, Bristol Myers Squibb, Pfizer, Actuate, Vyriad, Nanobiotix, Seattle Genetics, AstraZeneca, Molecular Templates, and Sorrento to their institution, consulting fees from Bristol Myers Squibb to their institution, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alkermes to their institution. CPR declares grants or contracts from AstraZeneca, Ayala, BMS, Cue Biopharma, Merck, Prelude, Sanofi Aventis, and Seagen to their institution, consulting fees from Vaccitech and Adaptimmune, and participation on a data safety monitoring board or advisory board at Pionyr Therapeutics. AGS declares grants or contracts from Merck, Bicara, AstraZeneca, Genentech/Roche, ALX Oncology, Regeneron, and Infinity Pharmaceuticals to their institution, consulting fees from Bicara, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from i3Health. VT declares grants or contracts from NIH and Veteran's Administration, support for attending meetings or travel from the American Society for Radiation Oncology and the American Board of Radiology, and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Cardiff Oncology. PAT-S declares support for the current manuscript from NRG Oncology Statistics and Data Management Center grant from NCI. TW-D declares grants or contracts from Bristol Myers Squibb, Merck, Janssen, AstraZeneca/Medimmune, and Tesaro/GSK, and participation on a data safety monitoring board or advisory board at Merck. SSY declares grants or contracts from Bristol Myers Squibb and EMD Serono to their institution, honoraria for editorship from Elsevier, and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at ASTRO for editorship. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Hypoxia-inducible factor 1α (HIF1α) is a master regulator of biological processes in hypoxia. Yet, the mechanisms and biological consequences of aerobic HIF1α activation by intrinsic factors, particularly in normal (primary) cells, remain elusive. Here we show that HIF1α signalling is activated in several human primary vascular cells in normoxia and in vascular smooth muscle cells of normal human lungs. Mechanistically, aerobic HIF1α activation is mediated by paracrine secretion of three branched-chain α-ketoacids (BCKAs), which suppress PHD2 activity via direct inhibition and via LDHA-mediated generation of L-2-hydroxyglutarate. BCKA-mediated HIF1α signalling activation stimulated glycolytic activity and governed a phenotypic switch of pulmonary artery smooth muscle cells, which correlated with BCKA metabolic dysregulation and pathophenotypic changes in pulmonary arterial hypertension patients and male rat models. We thus identify BCKAs as previously unrecognized signalling metabolites that aerobically activate HIF1α and that the BCKA-HIF1α pathway modulates vascular smooth muscle cell function, an effect that may be relevant to pulmonary vascular pathobiology., Competing Interests: Competing interests: J.L. discloses scientific board/board relationships with Ionis (outside the scope of the current topic), Leap Therapeutics (outside the scope of the current topic) and Scipher Medicine (outside the scope of the current topic). B.M.W. discloses a consulting relationship with Change Healthcare (outside the scope of the current topic), an expert witness relationship with United Therapeutics Corporation (outside the scope of the current topic) and co-inventorship on US patent 63/541,939 (outside the scope of the current topic). All other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Psychologists are well-positioned to take on leadership roles in health care systems as a result of the broad-based skills included in doctoral level, professional training programs. These include knowledge of evidence-based practice, extensive training in applied research and clinical practice, emphasis on critical thinking in scientific methods and hypothesis testing, teaching, supervision, team consultation, and continuous learning (APA Presidential Task Force on Evidence-Based Practice, 2006; Korman, 1974; McFall, 2007). Formal opportunities to learn how to apply these skills in leadership and organizational management roles are, however, limited during graduate training. There have been recent efforts within the American Psychological Association to foster interest and readiness for leadership roles among psychologists. These efforts have included a leadership development fellowship, on-demand webinars, and online learning for continuing education (American Psychological Association, 2023). The content of these training opportunities is typically general in nature so that it can be applied to all types of organizational settings. Psychologists interested in leadership positions within public sector health care organizations are likely to benefit from information that aligns more specifically with the mission and organizational structures of such systems. This article presents a conceptual framework to prepare psychologists aspiring to leadership positions in public sector health care. Leadership theories and models from organizational management science are outlined which capture the context and organizational goals of such programs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations., Methods: A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils., Results: A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic "for-cause" procedures were independently associated with higher quantities of TBBx eosinophils., Conclusions: Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms., Methods: All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome., Results: A total of 142 patients were confirmed to have had an episode of septic arthritis in a native hip (n = 17) or knee joint (n = 125). S. aureus accounted for 57.7% of all hip and knee joint infections. There were 13 inpatient deaths attributed to septic arthritis. The median age of the patients who died was 77.5 (46.9 to 92.2) and their median age-adjusted CCI was 8 (6 to 12). A failure of the joint occurred in 26 knees (21%) and nine hips (53%). Of the knee joints infected by S. aureus (n = 71), 23 knees (32%) went into failure of joint, whereas of those infected by other organisms (n = 54), only three knees (6%) failed., Conclusion: Based on our study findings, hip and knee septic arthritis long-term outcomes were substantially worse than their immediate outcome suggested. Failure of knee joint is 6.1 times more likely to occur in those infected with S. aureus ., Competing Interests: R. G. E. Clement discloses a Royal College of Surgeons of Edinburgh/Cutner Fellowship grant, a Tenovus small grant fund, and a Royal College of Edinburgh small grant fund related to this work. A. H. R. W. Simpson declares grants from RCUK, charities, and Stryker, unrelated to this paper., (© 2024 Clement et al.)

Objectives: Evaluate pediatric auditory brainstem response (ABR) findings in children with Autism Spectrum Disorder (ASD) after the 2013 DSM-5 update., Study Design: This was an IRB-approved, six-year retrospective chart review evaluating ABR results from pediatric patients with speech delay. Diagnosis of ASD and other neurodevelopmental abnormalities were collected for patient stratification., Methods: From 2017 to 2023, 148 pediatric patients with speech delay were identified through diagnosis of speech delay and underwent ABR testing. Patients were then separated into two groups: Neurotypical (N = 79) and ASD (N = 69). ABR results were obtained through chart review and waveform and interpeak latency (IPL) results were recorded. Differences in waveform and IPL results were determined via Pearson's chi-square test, with multivariate analysis accounting for race, sex, and age., Results: 28 patients with ASD (40.6 %) had at least one waveform/IPL prolongation. Analysis showed an increased incidence of waveform III (p = 0.028) and IPL III-V (p = 0.03) prolongation in the ASD group compared to their neurotypical counterparts. Waveform III prolongation was noted more in females with ASD (p = 0.001) than in males. No statistically significant difference when comparing race and age was found, except in the 2-3 age range (p = 0.003)., Conclusions: There were higher percentages of prolongation for all waveforms and IPLs in the ASD group versus neurotypical, though not as high as previously reported. Race and age did not appear to be factors in ABR findings though more data is needed to make clinical associations., Competing Interests: Declaration of competing interest This work's authors do not have any conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS)., Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation., Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023., Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks., Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers., Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed., Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation., Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.

Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur. We then used immune deconvolution of RNA sequencing datasets to evaluate immunologic cell subset enrichment. This identified M2 macrophage signaling associated with type I IFN pathway expression in RT-recurrent disease. To further dissect mechanism, we then evaluated differential gene expression between pre-treatment and RT-resistant HNCs from sampled from the same patients at the same anatomical location in the oral cavity. Here, recurrent samples exhibited upregulation of type I IFN-stimulated genes (ISGs) including members of the IFN-induced protein with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane (IFITM) gene families. While several ISGs were upregulated in each recurrent cancer, IFIT2 was significantly upregulated in all recurrent tumors when compared with the matched pre-RT specimens. Based on these observations, we hypothesized sustained type I IFN signaling through ISGs, such as IFIT2, may suppress the intra-tumoral immune response thereby promoting radiation resistance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2104/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: Onychocryptosis, or ingrown toenail, is a common condition affecting patients of varying age groups, although usually, younger patients are affected., Methods: We compared two techniques used in our institution: Winograd wedge resection with matrixectomy (WG-M) versus partial nail avulsion with phenolization of the nail matrix (PNA-P)., Results: Primary outcomes of interest were presence of nail regrowth and patient satisfaction postoperatively. Secondary outcomes were postoperative pain (within the first 2 weeks and after 2 weeks), postoperative inflammation, and healing time. A total of 65 patients were included in this study: 44 patients (19 female and 25 male patients), with a mean age of 45.7 years (range, 16-83 years) underwent WG-M in the orthopedic surgery department, whereas a total of 21 patients (10 female and 11 male patients), with a mean age of 44.5 years (range, 13 to 75 years) underwent PNA-P in the podiatry department. In patients who underwent WG-M, there was one case of regrowth (2.3%) compared with no regrowth cases (0%) in the PNA-P group. There was no significant difference in regrowth rate between the two procedures (P = .494). The satisfaction rate was high for both procedures: 100% patients in the WG-M group rated themselves better than before surgery, compared with 95.7% in the PNA-P group., Conclusions: From our study, we conclude that both techniques (WG-M and PNA-P) are able to achieve similar clinical outcomes, with the PNA-P procedure being less invasive and less resource intensive, and also achieving a shorter healing time.

Introduction: Massive rotator cuff tears (MRCTs) have long posed a complex problem for both patients and surgeons. If not treated promptly, tendon retraction, fatty infiltration and muscle atrophy of the rotator cuff muscles occur. These lead to irreparable RCTs with poor functional outcomes. We describe our technique of superior capsular reconstruction (SCR) augmented with partial cuff repair and report on our short term outcomes., Method: Seven consecutive patients who underwent the procedure were recruited at our institution from January 2019 to December 2019. Medical records of these patients were reviewed looking at pre-operative symptoms and examination findings, imaging studies, intra-operative findings, the surgical technique employed, post-operative progress in terms of pain, affected shoulder range of movement and outcome scores., Results: All patients showed complete tears of at least two tendons and were deemed irreparable intra-operatively. All patients exhibited Goutalier grade 2-4 wasting of the affected tendons on MRI and Patte grade 3 intra-operatively. At 12 months, the mean improvement shown in Constant score is 12.1 points, in University of California Los Angeles (UCLA) score is 9.4 points and in Oxford Shoulder Score is 17 points. Active forward flexion improved in all patients with a mean improvement of 40 degrees. Numerical Pain Rating Scale improved in all patients with a mean of 5.1 points., Conclusion: Our case series shows good short-term outcomes can be achieved with SCR augmented with partial cuff repair. Notably, our SCR results showed encouraging results even for challenging revision rotator cuff repairs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Importance: Patients with locally advanced non-human papillomavirus (HPV) head and neck cancer (HNC) carry an unfavorable prognosis. Chemoradiotherapy (CRT) with cisplatin or anti-epidermal growth factor receptor (EGFR) antibody improves overall survival (OS) of patients with stage III to IV HNC, and preclinical data suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and ERBB2 (formerly HER2 or HER2/neu) inhibitor may be more effective than anti-EGFR antibody therapy in HNC., Objective: To examine whether adding lapatinib, a dual EGFR and HER2 inhibitor, to radiation plus cisplatin for frontline therapy of stage III to IV non-HPV HNC improves progression-free survival (PFS)., Design, Setting, and Participants: This multicenter, phase 2, double-blind, placebo-controlled randomized clinical trial enrolled 142 patients with stage III to IV carcinoma of the oropharynx (p16 negative), larynx, and hypopharynx with a Zubrod performance status of 0 to 1 who met predefined blood chemistry criteria from October 18, 2012, to April 18, 2017 (median follow-up, 4.1 years). Data analysis was performed from December 1, 2020, to December 4, 2020., Intervention: Patients were randomized (1:1) to 70 Gy (6 weeks) plus 2 cycles of cisplatin (every 3 weeks) plus either 1500 mg per day of lapatinib (CRT plus lapatinib) or placebo (CRT plus placebo)., Main Outcomes and Measures: The primary end point was PFS, with 69 events required. Progression-free survival rates between arms for all randomized patients were compared by 1-sided log-rank test. Secondary end points included OS., Results: Of the 142 patients enrolled, 127 (median [IQR] age, 58 [53-63] years; 98 [77.2%] male) were randomized; 63 to CRT plus lapatinib and 64 to CRT plus placebo. Final analysis did not suggest improvement in PFS (hazard ratio, 0.91; 95% CI, 0.56-1.46; P = .34) or OS (hazard ratio, 1.06; 95% CI, 0.61-1.86; P = .58) with the addition of lapatinib. There were no significant differences in grade 3 to 4 acute adverse event rates (83.3% [95% CI, 73.9%-92.8%] with CRT plus lapatinib vs 79.7% [95% CI, 69.4%-89.9%] with CRT plus placebo; P = .64) or late adverse event rates (44.4% [95% CI, 30.2%-57.8%] with CRT plus lapatinib vs 40.8% [95% CI, 27.1%-54.6%] with CRT plus placebo; P = .84)., Conclusion and Relevance: In this randomized clinical trial, dual EGFR-ERBB2 inhibition with lapatinib did not appear to enhance the benefit of CRT. Although the results of this trial indicate that accrual to a non-HPV HNC-specific trial is feasible, new strategies must be investigated to improve the outcome for this population with a poor prognosis., Trial Registration: ClinicalTrials.gov Identifier: NCT01711658.

Background: Virtual reality simulations are shown to be an effective approach for interprofessional nurse-physician communication training. However, its scalability is constrained by unequal medical-nursing cohort size, rendering a great challenge for all nursing students to form an interprofessional team with medical students. With the evolution of artificial intelligence (AI), an AI medical team player can be integrated into virtual reality simulations for more nursing students to engage in interprofessional team training., Objectives: To describe the development of a novel AI-enabled virtual reality simulation (AI-enabled VRS) and to evaluate nursing students' competencies and experiences in communicating with an AI medical doctor., Methods: A mixed-methods design using a one-group pretest-posttest design and focus group discussions were employed in the evaluation phase. Nursing students from a university were recruited to undertake the 2-hour AI-enabled VRS. Pre-test and post-tests were administered to evaluate the participants' communication knowledge and self-efficacy. Survey questionnaires were administered to examine their experiences with the virtual reality environment and the AI doctor. Five focus group discussions were conducted to gain deeper insight into their learning experiences., Results: The participants demonstrated significant improvements in communication knowledge and interprofessional communication self-efficacy after the learning. They reported positively on the acceptability, feasibility and usability of the AI-enabled VRS. The subscale of "human-like" feature of the AI medical doctor was rated the lowest. Three themes surrounding participants' experiences of the virtual learning emerged: "relate to the real world", "artificial intelligence versus human intelligence" and "complement with face-to-face learning"., Conclusions: This study demonstrates initial evidence on the potential of AI-enabled VRS in fostering nursing students' learning on interprofessional communication skills. The findings have also provided insights on how to improve the AI-enabled VRS, in particular, the expressiveness of the AI pedagogical agent and facilitating more dialogue trainings with learner-agent conversations., Competing Interests: Conflict of interest No conflict of interest has been declared by the authors., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population., Methods: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m 2 ) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m 2 ), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete., Findings: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group)., Interpretation: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated., Funding: National Cancer Institute and Novartis., Competing Interests: Declaration of interests KCB declares in the past 36 months an unpaid chair of the Americans Thyroid Association Anaplastic Thyroid Cancer Guidelines Task Force, now published. CHC declares in the past 36 months participation on a Data Safety Monitoring Board or Advisory Board for Bristol-Myers Squibb, Cue Biopharma, Sanofi, Mirati, Merck, Brooklyn ImmunoTherapuetics, and Exelixis. MFD declares in the past 36 months support for attending Radiation Oncologists (PA, USA), American Society for Radiation Oncology (ASTRO) Head and Neck Meeting (Scottsdaye, AZ, USA), 2020 ASTRO Annual Meeting (San Antonio, TX, USA); and reimbursement for travel, registration and food, Health Policy Committee Payer Relations for ASTRO. RLF declares in the past 36 months royalties from Bionix TruGuard oral stent, paid to the Mayo Clinic and to himself, honoria for lecture ITCCIR 2021, Elsevier royalties for providing content for sale textbook as Editor, and Hitachi-unrestricted use of research funds paid to the Mayo Clinic for named professorship (Hitachi Professor of Radiation Oncology Research). RAG declares in the past 36 months receipt of National Institutes of Health grant P30CA008748 to the Memorial Sloan Kettering Cancer Center. SAK declares in the past 36 months research support from Merck, Bristol Myers Squibb, and Castle BioSciences; consulting fees from Regeneron; Merck-paid advisory board; an unpaid advisory board role at Castle BioSciences; author for UpToDate; and a data safety monitoring board role at AlphaTau. NYL declares in the past 36 months advisory board roles at Pfizer, Merck, Merck EMD, Elsie, and Mirati. Q-TL declares in the past 36 months consultant roles for Nanobiotix, Roche, and Coherus; honoraria from Johns Hopkins Lecture and 2021 China International Exchange, and Promotive Association for Medical and Health Care Nasopharyngeal Cancer Branch Inaugural Conference and Minimally Invasive Surgery Training Course of Nasopharyngeal Cancer, paid flights or hotels Radiation Therapy Oncology Group (RTOG) foundation meetings or retreats, RTOG group chair (NRG Oncology), and stock or stock options exceeding US$1000 from Aldea. NR reports since the initial planning of the work research support from Pfizer, Repertoire, REPARE Therapuetics, and BMS, and in the past 36 months consulting fees from Illumina Paige.AI. MHS declares in the past 36 months grants from Merck and Eli-Lilly for clinical trials with payment made to his institution. EJS reports since the initial planning of the work support from GSK/Novartis (no payment) and in the past 36 months consulting fees from Eli Lilly, Roche, Regeneron, Eisai, and Elixis, advisory board roles (no compensation) with Eli Lilly, Novartis, and DSMB, and a Protocol Chair (unpaid) role with Eli Lilly and Novartis. PAT-S reports since the initial planning of the work NRG Oncology Statistics and Data Management Center grant from the National Cancer Institute (NCI). PX declares in past 36 months payment to his institution, research grants from AVO and Philips, and support from Philips to present at a Sun Nuclear QA meeting in 2019. SSY declares in past 36 months research support paid to his institution from Merck, Bristol-Myers Squibb, EMD Serono, Genentech, and BioMimetix; book chapter royalties from Springer and UpToDate; and service positions at ASTRO, Elsevier, and NRG Oncology. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical studies to overcome the key limitation of poor patient compliance often reported in cancer chemoprevention trials. Both matrine and dictamine were detected in the saliva and plasma samples but only matrine was quantifiable after the oral administration of ATB tablets (2400 mg) in 8 healthy volunteers. A significantly high saliva/plasma ratios for C max (6.5 ± 2.0) and AUC 0-24 (4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t 1/2 plasma = 10.0 ± 2.8 h, t 1/2 saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient's compliance to the treatment regimen in upcoming clinical trials of ATB.

Objective: The purpose of this study is to assess the anatomical appropriateness of a three-dimensional (3D) printed pediatric middle ear model with a replaceable middle ear unit as an endoscopic ear surgery (EES) simulator., Methods: Single-blinded, prospective, proof-of-concept study conducted in a simulation operative suite. A simulator was developed through segmentation of source images and multi-material 3D printing. Subjects were asked to point to seven anatomical sites before and after a short anatomy presentation of a human middle ear photograph. They also filled out a survey about the feasibility of the model. Outcome variables included survey scores, pre-anatomy lesson (PreAL) and post-anatomy lesson (PostAL) quiz scores., Results: There were 24 participants (19 residents, 1 fellow, and 4 attendings), none with self-reported proficiency in EES. The PreAL mean score was 4.42 and PostAL quiz mean score was 5.32 (average improvement of 43% [CI = 17%-70%]; p  = .003). The higher the level of training, the higher the PreAL scores (0.55 points per year of training; p  = .004). The subspecialty (otology, other, in-training) was also associated with the PreAL scores ( p  = .004). Total survey score means were 22.8 (out of 30)., Conclusion: The results of our study suggest that our model has adequate anatomical high fidelity to mimic a real, pediatric temporal bone for EES. As 3D printing technologies continue to advance, the quality of ear models has the potential to provide improved surgical training for pediatric EES., Level of Evidence: 4., Competing Interests: None., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Aims: Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal's immune response to infection., Methods: Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10 7 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling., Results: Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed., Conclusion: Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage.Cite this article: Bone Joint Res  2022;11(9):669-678.

Background and Aim: The small endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs), gastric subepithelial tumors at the muscularis propria layer on EUS, are detected frequently. Bite-on-bite forceps biopsy and EUS-guided tissue sampling yield variable results. This study aimed to analyze clinicopathologic features of the small EUS-suspected gastric GISTs 2 cm or less in size and to evaluate the efficacy and safety of the endoscopic incisional biopsy (EIB) for these small tumors., Methods: This prospective study investigated 70 patients with small EUS-suspected gastric GISTs 2 cm or less in size in two stages. Firstly, 30 patients were recruited for the efficacy and safety evaluation of the EIB. Secondly, 40 patients were randomly assigned to receive either EIB or the bite-on-bite biopsy for comparison of the diagnostic yield, procedure time, and adverse event rate., Results: Combining two study stages, leiomyoma (74%) was diagnosed histologically to outnumber GIST (26%) with a diagnostic rate of 94% for patients receiving EIB. KIT exon 11 mutations (50%) and PDGFRA exon 12 mutations (16%) were detected in the small gastric GISTs. In the direct comparison, the diagnostic yield of EIB and the bite-on-bite biopsy was 85% and 50%, respectively (P = 0.018). There was no statistically significant difference of the mean procedure time or adverse event rate between these two groups., Conclusions: Leiomyoma is more common than expected among these small tumors. Tissue diagnosis with an effective and safe sampling technique, such as EIB, is necessary for making further clinical decisions., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach., Methods: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction. Patients underwent topical preparation of the oral mucosa with povidone-iodine (PI) and chlorhexidine gluconate (CHG) pre- and intra-operatively followed by oral tetracycline ointment every 6 hours for 2 days post-operatively. The primary outcome was change in bacterial bioburden at the oral surgical site. Secondary outcomes included safety, SSI, and microbial predictors of infection., Findings: Of 27 patients screened between January 8, 2021, and May 14, 2021, 26 were enrolled and 25 completed the study. There were no antiseptic-related adverse events. The topical mucosal antiseptic bundle significantly decreased oral bacterial colony-forming units from pre-operative levels (log 10 mean difference 4·03, 95%CI 3·13-4·;92). There were three SSI (12%) within 30 days. In correlative genomic studies, a distinct set of amplicon sequence variants in the post-operative microbiome was associated with SSI. Further, despite no instance of post-operative orocervical fistula, metagenomic sequence mapping revealed the oral cavity as the origin of the infectious organism in two of the three SSI., Interpretation: The bacterial strains which subsequently caused SSI were frequently identified in the pre-operative oral cavity. Accordingly, a topical antiseptic bundle decreased oral bacterial bioburden throughout the peri-operative period and was associated with a low rate of SSI, supporting further study of topical antisepsis in HNC surgery., Funding: Alliance Oncology., Competing Interests: Declaration of interests None., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives/hypothesis: For most pediatric specialty clinics, mental health is not the primary presenting complaint, yet can portend unrecognized morbidity. We describe rates and risk factors of depression and suicidal ideation in adolescents seen at a pediatric specialty clinic and examine changes during COVID-19., Study Design: Retrospective database review., Methods: Outpatient pediatric otolaryngology clinic encounters of patients aged 12-19 years at a tertiary academic medical center were identified from October 2018 to July 2020. Demographic characteristics, ICD-10 primary diagnosis, Patient Health Questionnaire (PHQ)-2 score, and PHQ-9 score (if administered) were obtained. Multivariable regression examined risk factors for PHQ-9 administration, PHQ-9 scores ≥10, and suicidal ideation. Patient characteristics and PHQ scores were compared before and after March 23, 2020 (California COVID-19 Stay-at-Home order)., Results: Three thousand six hundred nine encounters with PHQ-2 data were identified. Of these, 223 (6.2%) scored ≥3 and underwent PHQ-9 assessment, of which 121 (3.4% of 3,609) scored ≥10 on the PHQ-9 and 53 (1.5%) endorsed suicidal ideation. Factors associated with PHQ-9 administration were female gender (odds ratio [OR] 1.58, P = .001), obesity (OR 1.48, P = .043), and neck mass/neoplasm/cancer diagnosis (OR 1.99, P = .013). Female gender was also associated with suicidality (OR 2.47, P = .008). Comparison of pre-COVID-19 versus during COVID-19 showed no differences in depression or suicidality. However, subgroup analysis revealed some significant findings., Conclusions: We demonstrate substantial prevalence of positive depression screening and suicidal ideation among adolescent pediatric otolaryngology clinic encounters. Depression rates were similar to pre-COVID-19 and during COVID-19, yet barriers to screening during this time were substantial. Pediatric specialty providers must remain vigilant for mental health issues in their patients., Level of Evidence: 3 Laryngoscope, 132:1104-1111, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas., Methods: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection., Results: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite., Conclusions: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported., (Published by Oxford University Press on behalf of International Society of Travel Medicine 2021.)

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune-related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically-diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1-high, CTLA4-high, antigen-presentation, and pro-angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1-high and CTLA4-high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)