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Introduction: Esophageal Stents are used to maintain esophageal lumen patency in esophageal strictures caused by intrinsic and/or extrinsic malignancies and the occlusion of concomitant esophageal fistulas. While data on the efficacy and safety of esophageal stents exist, comprehensive evaluation of adverse events is limited. The aim of this study is to investigate the reported adverse events and device failures associated with esophageal self-expandable metal stents (SEMS) using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database., Methods: Post-marketing surveillance data for the esophageal SEMSs were analyzed using the FDA's MAUDE database from January 2014 to December 10, 2023. The outcomes of interest were patient-related adverse events and device failures. Statistical analysis was performed using Microsoft Excel 2010 and SPSS. Pooled numbers and percentages were calculated for each adverse event. Continuous variables underwent analysis using a two-tailed student t test, and significance was set to p ≤ 0.05., Results: During the study period, 548 MAUDE reports revealed 873 device failures and 186 patient-related adverse events. The most common device issues were stent activation, positioning, or separation problems (4 n = 403; 46.2%), followed by device detachment or migration (n = 109, 12.5%), and material problems (n = 93, 10.7%). Patient complications included dysphagia/odynophagia (10%), perforation, pain, and bleeding (each 7.6%). The most common device failures in over-the-wire (OTW) stents and through-the-scope (TTS) stents were activation, positioning, or separation problems (TTS: n = 183, 52.6% vs OTW: n = 220, 41.9%). Compared to OTW stents, TTS stents had higher migration and breakage (13.5% vs. 11.8%, p = 0.24), and (9.2% vs. 6.7%, p = 0.08) respectively, while OTW stents had more challenges with stent advancement or removal (5.1% vs. 0.3%, p < 0.001 and 4.6% vs 3.4%, p = 0.19, respectively) and material problems (14.7% vs. 4.6%, p < 0.001). Activation, positioning, and separation problems were the most frequent device failures in fully covered (FC) and partially covered (PC) stents (FC: n = 62, 32.8%, PC: n = 168, 43.5%). FC stents had higher migration rates (20.6% vs 9.8%, p < 0.001), while PC stents exhibited more material problems (17.4% vs. 5.8%, p < 0.001) and difficulties with advancing the stents (6.7% vs. 0%, p < 0.001)., Conclusion: Our examination showed a prevalence of reported device complications associated with stent activation, positioning, and separation problems. Dysphagia or odynophagia emerged as the most frequently reported patient complication. Furthermore, our analysis, provides insights into TTS vs. OTW and FC vs. PC esophageal SEMSs, enabling endoscopists and manufacturers to better understand adverse events and potentially optimize device design for future iterations., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Emerging evidence in preclinical models demonstrates that antitumor immunity is not equivalent between males and females. However, more investigation in patients and across a wider range of cancer types is needed to fully understand sex as a variable in tumor immune responses. We investigated differences in T-cell responses between male and female patients with lung cancer by performing sex-based analysis of single cell transcriptomic datasets. We found that the transcript encoding CXC motif chemokine ligand 13 (CXCL13), which has recently been shown to correlate with T-cell tumor specificity, is expressed at greater levels in T cells isolated from female compared with male patients. Furthermore, increased CXCL13 expression was associated with response to PD1-targeting immunotherapy in female but not male patients. These findings suggest that there are sex-based differences in T-cell function required for response to anti-PD1 therapy in lung cancer that may need to be considered during patient treatment decisions. See related Spotlight by Cruz-Hinojoza and Stromnes, p. 952., (©2024 American Association for Cancer Research.)

Introduction: Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC., Materials and Methods: In adherence to PRISMA guidelines, a systematic literature review was conducted from 1950 to April 2024 using PubMed. The search focused on articles where TC was identified as the primary etiology of PE. The Mixed Methods Appraisal Tool and the Oxford Centre for Evidence-Based Medicine's levels of evidence tool were employed for assessing study quality, and a thematic analysis was conducted to identify trends and patterns., Results: Out of 91 articles identified, 29 met the inclusion criteria, encompassing 5 retrospective chart reviews, 3 case series, and 22 case reports. Findings indicate that PE symptoms can manifest at any stage of TC-before tumor detection, during treatment, or even years posttreatment. A notable observation was the frequent oversight of microscopic testicular tumors in ultrasound imaging, leading to diagnostic delays. The outcomes of PE in the context of TC were diverse, reflecting the heterogeneity of the studies included., Conclusion: PE, although rare, is a critical consideration in patients with TC presenting with neuropsychiatric symptoms. Early recognition and appropriate diagnostic workup, including consideration for microscopic neoplasms, are essential for timely intervention and improved patient outcomes., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Audience: This small-group workshop is designed for pre-clinical medical students. The workshop can also be offered to other medical students looking to review first aid in the community setting., Introduction: First aid training in medical students varies based on each student's previous experience. Because of this, medical students in their pre-clinical years have expressed a desire for further training in first aid.1 While most bystanders in an emergency situation do not have a medical background, medical students have received additional training that can provide the skillset to process and respond to emergency situations in a different capacity. Most medical schools have not adopted a universal curriculum in teaching medical students first aid.2 Incorporating first aid into a medical school curriculum can enhance medical students' confidence in emergent situations and lead to better outcomes for patients requiring immediate on-site care., Educational Objectives: The goal of this workshop was to improve the confidence of medical students in handling emergencies in the community with the use of first aid while also giving them a standard approach to emergencies using an airway, breathing, and circulation approach. The curriculum was evaluated through student-perceived self-efficacy and confidence in handling the provided scenarios, performance on relevant multiple choice questions, and general appeal of the first aid sessions. By the end of this workshop, students will be able to define the goals of "first aid" and first responder actions, describe clinical signs and symptoms suggestive of an airway, breathing, or circulation emergency in the setting of selected medical emergencies, and demonstrate immediate care steps in the setting of selected medical emergencies, specifically the Heimlich maneuver on adults and infants, direct pressure, wound packing, tourniquet application for external bleeding, epinephrine auto-injector administration, and the recovery position for obtunded or unconscious patients., Educational Methods: Small group activities were performed with a focus on case-based scenarios combined with hands-on instruction. The four scenarios were choking, seizure, anaphylaxis, and bleeding which were taught by an educator who was either faculty, an emergency medicine resident, or an upper-level medical student. Facilitators were provided an educational handout specific to their station to guide them through the teaching session. A PowerPoint presentation was also provided complete with supporting images and videos to share with the students each session., Research Methods: Students were asked to complete a pre-test and post-test survey to assess knowledge outcome, self-efficacy in first aid, and overall appeal of the workshop. The multiple-choice knowledge outcome data was scored for percent correct on each question as well as overall performance on questions grouped by content. Students were also asked to provide feedback and comments on their overall experience in the workshop., Results: Overall, medical students reported increased knowledge and confidence in responding to various first-aid situations. There was overall improvement in pre-test and post-test evaluations. The appeal of the event as a whole and its usefulness was overwhelmingly viewed as positive. Some participants noted they wanted similar workshops with more first-aid topics. Participants also noted they felt better prepared to respond to the various emergencies included in the workshop., Discussion: A workshop directed at teaching first aid to medical students increased their confidence and knowledge in responding to various emergencies and can successfully be accomplished through a focused large group didactic session and multiple clinically relevant small group teaching sessions., Topics: First aid, airway, breathing, circulation, medical students, choking, seizures, bleeding, anaphylaxis., (© 2024 Stodola, et al.)

A 69-year-old female with Crohn's disease was admitted for open ileocecectomy with lysis of adhesions. The plan was to proceed with general endotracheal anesthesia and a thoracic epidural catheter for perioperative analgesia. Epidural access was attempted at the T10-11 and T11-12 interspaces, both of which resulted in accidental dural punctures. On the third attempt, the epidural catheter was inserted at the T9-10 interspace. Both the aspiration and test dose were negative. Thirty minutes later, after induction of general anesthesia, the catheter was again aspirated before the epidural pump was connected. Freely flowing, glucose-positive fluid was obtained, and the catheter was removed for the patient's safety. This case suggests that accidental dural puncture may be a risk factor for inappropriate communication with the subarachnoid space. This can be assumed to increase the risk of unanticipated high or total spinal block and its life-threatening sequelae., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Arnaut et al.)

Background: Total shoulder arthroplasty frequently is performed in patients with a history of shoulder surgery. The purpose of this study was to evaluate clinical outcomes after primary shoulder arthroplasty in patients with a history of nonarthroplasty shoulder surgery, and whether certain modifiable risk factors (MRFs) were negatively associated with final outcome measures. The secondary purpose was to determine if costs or complications were higher in patients with prior shoulder surgery., Methods: We conducted a retrospective cohort study of all patients who underwent primary shoulder arthroplasty from January 2015 to December 2019 by one surgeon at one institution. Patients who received hemiarthroplasty were excluded. Univariate analysis was performed to assess the influence of prior shoulder surgery on costs, complications, and patient-reported outcome measures. Multivariable analysis was performed to determine if MRF negatively affected results, defined as anemia, malnutrition, obesity, uncontrolled diabetes, tobacco use, and opioid use., Results: 512 patients met inclusion criteria; 139 patients had at least one prior shoulder surgery. Patients with history of prior shoulder surgery were younger (65.2 ± 9.3 years vs. 70.7 ± 9.1 years, P  < .001), more likely to be male (52.2% vs. 47.8%, P  = .016), more likely to have smoking history (20.1% vs. 10.5%, P  = .002), and borderline more likely to use preoperative opioids (47.5% vs. 38.9%, P  = .078) while reporting significantly higher pain scores at final follow-up (visual analog scale for pain 1.7 ± 2.4 vs. 1.1 ± 1.9, P  = .001) and lower patient-reported outcome measure ( P  ≤ .017 for all). The final American Shoulder and Elbow Surgeons score (ASES) score was independently negatively impacted by a history of prior surgery ( β  = -4.25 (-7.92, -0.56), P  = .024) and other nonmodifiable factors including prosthesis type of reverse arthroplasty ( β  = -6.31, confidence interval [CI] -10.02, -2.60, P  = .001), cardiac disease ( β  = -3.59, CI -7.12, -.0.07, P  = .046), and any complication ( β  = 0.28, CI 0.19, 0.36, P  < .001). The final ASES score was negatively impacted by MRF including opioid use ( β  = -4.08, CI: -7.32, -0.84, P  < .001) and smoking status ( β  = -7.59, CI: -12.69, -2.49, P  < .001). Males had slightly higher final ASES scores ( β  = 3.79, CI 0.46, 7.11, P  = .026). Patients with prior surgery were more likely to have an intraoperative stress fracture [odds ratio [OR] 4.6 (1.1, 19.5), P  = .038] and borderline more likely to have neurologic complication [OR 1.7 (1.0, 3.0), P  = .062] or any complication [OR 1.5 (1.0, 2.3), P  = .075]., Conclusion: Patients with prior shoulder surgery were younger, more likely to be male, and more likely to have a history of tobacco use and opioid use. These patients experienced worse subjective clinical outcomes and were more likely to experience a complication., (© 2024 The Authors.)

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the SLC16A2 gene and resulting from dysfunctional thyroid hormone transport. This disorder is characterized by profound neurodevelopmental delay and motor disability due to a lack of thyroid hormone in the brain, and coexisting endocrinological symptoms, due to chronic thyrotoxicosis, resulting from elevated thyroid hormone outside the central nervous system (CNS). In February 2024, we reviewed the published literature to identify relevant articles reporting on the current unmet needs of patients with MCT8 deficiency. There are several main challenges in the diagnosis and treatment of MCT8 deficiency, with decreased awareness and recognition of MCT8 deficiency among healthcare professionals (HCPs) associated with misdiagnosis and delays in diagnosis. Diagnostic delay may also be attributed to other factors, including the complex symptomology of MCT8 deficiency only becoming apparent several months after birth and pathognomonic serum triiodothyronine (T3) testing not being routinely performed. For patients with MCT8 deficiency, multidisciplinary team care is vital to optimize the support provided to patients and their caregivers. Although there are currently no approved treatments specifically for MCT8 deficiency, earlier identification and diagnosis of this disorder enables earlier access to supportive care and developing treatments focused on improving outcomes and quality of life for both patients and caregivers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bauer, Auble, Clark, Hu, Isaza, McNerney, Metzger, Nicol, Pierce and Sidlow.)

Intranasal M2SR (M2-deficient Single Replication influenza virus) vaccine induces robust immune responses in animal models and human subjects. A high-throughput multiplexed platform was used to analyze hemagglutinin-specific mucosal antibody responses in adults after a single dose of H3N2 M2SR. Nasal swab specimens were analyzed for total and hemagglutinin-specific IgA. Significant, dose-dependent increases in mucosal antibody responses to vaccine-matched and drifted H3N2 hemagglutinin were observed in M2SR vaccinated subjects regardless of baseline serum and mucosal immune status. These data suggest that M2SR induces broadly cross-reactive mucosal immune responses which may provide better protection against drifted and newly emerging influenza strains., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Neuro-ophthalmic manifestations of Wernicke encephalopathy (WE) are uncommon and vary from nystagmus, oculomotor palsies, anisocoria, and optic disc edema to vision loss. We describe a case of a 53-year-old woman presenting with subacute bilateral painless vision decline, lower-extremities weakness with impaired ambulation, headache, and abdominal pain. Neurological examination was pertinent for confabulation, bilateral decreased visual acuity with an absent blink to threat, absent afferent pupillary defect and fundus abnormalities, and significant allodynia in bilateral lower extremities. Besides elevated inflammatory marker with an erythrocyte sedimentation rate (ESR) of 130 mm/hr, her infectious, autoimmune, paraneoplastic, and neuromyelitis optica work-up was overall unremarkable. Brain MRI showed abnormal fluid-attenuated inversion recovery (FLAIR) signaling in bilateral mammillary bodies and around periaqueductal gray matter concerning WE. Due to concerns of Wernicke-Korsakoff syndrome (WKS), parenteral high-dose thiamine was initiated with significant clinical improvement. The patient was also later found to have a positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody, which was deemed false positive given the atypical phenotype and symptomatic improvement with thiamine supplementation. This case encourages the consideration of vision loss as a manifestation of WKS, especially in patients who have risk factors. Testing serum levels of thiamine is strongly encouraged; however, initiating empiric treatment is advocated for high clinical suspicion due to its reversible nature and minimal risk for side effects., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Guagliardo et al.)

Substance misuse, traditionally seen as a problem of early to mid-adulthood, is becoming increasingly prevalent among the older adult population (ages ≥65). Diagnosing and treating substance misuse in this vulnerable population is challenging because of multiple pre-existing medical comorbidities as well as polypharmacy. As such, it remains underdiagnosed and underrepresented in the literature. This review provides an overview of the three most commonly misused substances in older adults: alcohol, cannabis, and prescription drugs. It examines epidemiology, societal trends, and treatment options, highlighting the need for targeted research to address the unique challenges faced by older adults. This review also briefly comments on the prevalence and treatment of other illicit drugs in this population., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Hu et al.)

Objective: The objectives of this study were to describe the incidence and morphology of medial tibial plateau fractures that extend into the lateral articular surface and to describe trends in their management., Design: Retrospective., Setting: Level I Urban Trauma Center., Patients: Seventy consecutive patients sustaining OTA/AO 41 B1 and B3 fractures., Intervention: Open reduction internal fixation of medial tibial plateau fractures., Main Outcome Measurements: Incidence of medial tibial plateau fractures that extend into the lateral articular surface. Secondary outcomes include localization of lateral articular surface depression, neurovascular injury, and trends in surgical management., Results: Seventy patients were included with 9 fractures (12.9%) isolated to the medial condyle (MC) and 61 fractures (87.1%) extending to the lateral condyle (LC). Compartment syndrome was present in 2 patients (2.9%), peroneal nerve palsy in 2 (2.9%), and arterial injury in 1 (1.4%). Initial external fixation was used more frequently in the LC group compared with the MC group ( P = 0.028). Of the 61 fractures in the LC group, 49 (80.3%) included lateral articular surface depression which localized to the posteromedial quadrant of the lateral articular surface in 36 of 49 fractures (73.5%). Lateral articular surface depression depth ≥10.6 mm was associated with the use of dual incisions ( P < 0.001)., Conclusions: Schatzker IV fractures frequently extend to the lateral condyle and often present with depression of the posteromedial lateral articular surface. Fractures with lateral articular surface depression depth ≥10.6 mm were more likely to undergo fixation with dual incisions., Level of Evidence: Therapeutic level IV., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: Minimally invasive surgical interventions for metastatic invasion of the pelvis have become more prevalent and varied. Our group hypothesized that the use of percutaneous photodynamic nails (PDNs) would result in decreased pain, improved functional outcomes and level of ambulation, and decreased use of opioid pain medication., Methods: We performed a retrospective chart review of patients with metastatic pelvic bone disease undergoing stabilization with PDNs (IlluminOss Medical) at 2 institutions. Functional outcome measures assessed include the Combined Pain and Ambulatory Function (CPAF), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, and PROMIS Global Health-Physical. Pain was assessed using a visual analog scale (VAS). Outcomes were assessed preoperatively and at 6 weeks, 3 months, 6 months, and 1 year following surgery., Results: A total of 39 patients treated with PDNs were included. No cases of surgical site infection or implant failure were identified. The median pain VAS score decreased from 8 preoperatively to 0 at the 6-week time point (p < 0.0001). The median CPAF score improved from 5.5 points preoperatively to 7 points at the 3-month mark (p = 0.0132). A significant improvement in physical function was seen at 6 months in the PROMIS Physical Function (p = 0.02) and at both 6 months (p = 0.01) and 1 year (p < 0.01) for the PROMIS Global Health-Physical. The rate of patients prescribed opioid analgesia dropped from 100% preoperatively to 20% at 6 months following surgery (p < 0.001). By 6 weeks, all patients were fully weight-bearing and able to walk independently with or without assistive devices., Conclusions: Percutaneous stabilization of metastatic periacetabular defects using PDNs is a safe and effective palliative procedure that has been shown to improve patient mobility and provide early pain relief., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Article Processing Charge for open access publication was funded by IlluminOss Medical Inc., the manufacturer of the photodynamic nails used in the procedures evaluated in this investigation. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A642)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Human adenoviruses can cause serious, disseminated infections in immunocompromised patients. For pediatric allogeneic stem cell transplant patients, the case fatality rate can reach 80%. Still, there is no available antiviral drug that is specifically approved by the Food and Drug Administration for the treatment of adenovirus infections. To fill this pressing medical need, we have developed NPP-669, a prodrug of cidofovir with broad activity against double-stranded DNA viruses, including adenoviruses. Here, we report on the in vivo anti-adenoviral efficacy of NPP-669. Using the immunosuppressed Syrian hamster as the model, we show that NPP-669 is highly efficacious when dosed orally at 1 mg/kg and 3 mg/kg. In a delayed administration experiment, NPP-669 was more effective than brincidofovir, a similar compound that reached Phase III clinical trials. Furthermore, parenteral administration of NPP-669 increased its efficacy approximately 10-fold compared to oral dosing without apparent toxicity, suggesting that this route may be preferable in a hospital setting. Based on these findings, we believe that NPP-669 is a promising new compound that needs to be further investigated., Competing Interests: The authors declare no conflict of interest.

Background and objective Providing care for a loved one with a chronic illness or disability can be mentally and emotionally challenging. Determining the factors that contribute to psychological distress among informal caregivers can be important in developing effective interventions to support this vulnerable population. This study aimed to examine the sociodemographic determinants of psychological distress among adult informal caregivers in the United States. Research design and method Secondary data analysis using the 2022 Health Information National Trends Survey was conducted. A total of 807 informal caregivers were included in the study. Sociodemographic characteristics, caregiving conditions, and caregivers' relationship to care recipients were assessed. Psychological distress was measured using Patient Health Questionnaire 4. Weighted multivariate logistic regression analysis was conducted to determine the associations between sociodemographic factors and psychological distress. Results The prevalence of psychological distress was 40%. The average age of the sample was 56 years with most caregivers being female and non-Hispanic White. Older age was associated with lower odds of distress (OR=0.974, 95% CI: 0.949-0.999). Female caregivers had higher odds of distress compared to males (OR=1.922, 95% CI: 1.023-3.612), and caregivers with household incomes of $75,000 or more had significantly lower odds of distress compared to those with incomes below $35,000 (OR=0.266, 95% CI: 0.119-0.595). Race/ethnicity and educational level did not show significant associations with caregiver distress. Conclusion Younger age, female birth gender, and lower household income were associated with higher odds of distress among informal caregivers. These findings can inform the development of targeted interventions to support caregivers' mental health., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Atuiri et al.)

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) dermatomyositis (DM) is a subset of amyopathic myositis and is associated with unique cutaneous manifestations and rapidly progressive interstitial lung disease (RP-ILD). A rare complication associated with high mortality is the occurrence of pneumomediastinum. We present a case of a 58-year-old female with anti-MDA5 DM-associated interstitial lung disease (ILD) complicated by pneumomediastinum. Treatment with pulse dose steroids and intravenous cyclophosphamide led to clinical improvement and resolution of the pneumomediastinum. Our case emphasizes the recognition of ILD-associated pneumomediastinum in patients with anti-MDA5 DM. Swift diagnosis and aggressive treatment are crucial due to the associated high mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Chaudhary et al.)

Concerns related to poor oxygenation in patients with severe hepatopulmonary syndrome (HPS) may be prohibitive when considering their candidacy for liver transplantation. Extracorporeal membrane oxygenation (ECMO) has been utilized in only a few case reports as a bridge to liver transplant in patients with severe respiratory failure. We report a case of a 66-year-old man with cirrhosis and very severe (arterial oxygen pressure (PaO2) < 50 mmHg) hepatopulmonary syndrome who underwent an orthotopic liver transplant with the planned use of venovenous-ECMO. Pre-transplant echocardiography demonstrated a small-trivial patent foramen ovale (PFO) but following the resolution of hepatopulmonary shunting after liver transplantation, the PFO size enlarged and contributed to a thromboembolic stroke. We conclude that well-selected patients with HPS could benefit from the use of planned venovenous-ECMO and that a small-trivial PFO seen in a patient with HPS may warrant intervention prior to transplantation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tyler et al.)

The primarily disordered C-terminal domain (CTD) of TAR DNA binding protein-43 (TDP-43), a key nuclear protein in RNA metabolism, forms neuronal inclusions in several neurodegenerative diseases. A conserved region (CR, spanning residues 319-341) in CTD forms transient helix-helix contacts important for its higher-order oligomerization and function that are disrupted by ALS-associated mutations. However, the structural details of CR assembly and the explanation for several ALS-associated variants' impact on phase separation and function remain unclear due to challenges in analyzing the dynamic association of TDP-43 CTD using traditional structural biology approaches. By employing an integrative approach, combining biophysical experiments, biochemical assays, AlphaFold2-Multimer (AF2-Multimer), and atomistic simulations, we generated structural models of helical oligomerization of TDP-43 CR. Using NMR, we first established that the native state of TDP-43 CR under physiological conditions is α-helical. Next, alanine scanning mutagenesis revealed that while hydrophobic residues in the CR are important for CR assembly, phase separation and TDP-43 nuclear retention function, polar residues down regulate these processes. Finally, pairing AF2-Multimer modeling with AAMD simulations indicated that dynamic, oligomeric assemblies of TDP-43 that are stabilized by a methionine-rich core with specific contributions from a tryptophan/leucine pair. In conclusion, our results advance the structural understanding of the mechanisms driving TDP-43 function and provide a window into the initial stages of its conversion into pathogenic aggregates., Competing Interests: Competing interests NLF was a consultant for Dewpoint Therapeutics.

Background: Biannual instrument-correlation studies are required for nonwaived assays performed on multiple instruments., Objective: To determine the feasibility of using College of American Pathologists (CAP) Quality Cross Check-Chemistry and Therapeutic Drug Monitoring (CZQ) to assess instrument correlations among multiple analyzers, analyzer models, and Clinical Laboratory Improvement Amendments (CLIA) licenses for 55 unique analytes., Methods: Instrument correlation studies were performed on 9 Abbott ARCHITECT instruments (c4000 [n = 4], c8000 [n = 2], and c16000 [n = 3]) over 3 CLIA licenses using CZQ materials. The mean (SD) values, concentration difference, percent bias, and peer data for each individual level of CZQ were determined for each individual analyzer. Acceptable concentration and percentage for each analyte were set using criteria from CAP or other reputable sources such as the American Association of Bioanalysts or the Royal College of Pathologists of Australasia. Peer data were provided by CAP with the CZQ kit., Results: Correlations using CZQ materials showed that 94.5% of assays studied were within the acceptability criteria by percent bias only and 98.2% were within acceptability criteria by concentration difference., Conclusions: The use of CZQ provides support to standardized correlation studies among instruments within and across separate CLIA licenses. However, widespread adoption of CZQ may be limited due to concerns regarding matrix effects, analyte ranges, and ease of data analysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Multiplexing of phosphatidylcholine analysis is hindered by a lack of appropriate derivatization. Presented here is a tagging scheme that uses a quaternary amine tag and targets the hydroxy group of the phosphate, which switches the net charge from neutral to +2. Quantitative yields were achieved from >99% reaction completion derived by dimethoxymethyl morpholinium (DMTMM) activation. Fragmentation of phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) releases two trimethylamines and the acyl chains through neutral loss and generates a unique double cyclization constant mass reporter. Selective incorporation of isotopes onto the tag produces a six-plex set of isobaric reagents. For equivalent six-plex-labeled samples, <14% RSD was achieved, followed by a dynamic range of 1:10 without signal compression. Quantification of PCs/LPCs in human hepatic cancer cells was conducted as six-plex using data-dependent analysis tandem MS. We report a six-plex qualitative and quantitative isobaric tagging strategy expanding the limits of analyzing PCs/LPCs.

Purpose: The purpose of this study was to evaluate the impact of vitrectomy and posterior hyaloid (PH) peeling on color alteration of optic nerve head (ONH) and retina as a surrogate biomarker of induced perfusion changes., Methods: Masked morphometric and colorimetric analyses were conducted on preoperative (<1 month) and postoperative (<18 months) color fundus photographs of 54 patients undergoing vitrectomy, either with (44) or without (10) PH peeling and 31 years of age and gender-matched control eyes. Images were calibrated according to the hue and saturation values of the parapapillary venous blood column. Chromatic spectra of the retinal pigment epithelium and choroid were subtracted to avoid color aberrations. Red, green, and blue (RGB) bit values over the ONH and retina were plotted within the constructed RGB color space to analyze vitrectomy-induced color shift. Vitrectomy-induced parapapillary vein caliber changes were also computed morphometrically., Results: A significant post-vitrectomy red hue shift was noted on the ONH (37.1 degrees ± 10.9 degrees vs. 4.1 degrees ± 17.7 degrees, P < 0.001), which indicates a 2.8-fold increase in blood perfusion compared to control (2.6 ± 1.9 vs. 0.9 ± 1.8, P < 0.001). A significant post-vitrectomy increase in the retinal vein diameter was also noticed (6.8 ± 6.4% vs. 0.1 ± 0.3%, P < 0.001), which was more pronounced with PH peeling (7.9 ± 6.6% vs. 3.1 ± 4.2%, P = 0.002)., Conclusions: Vitrectomy and PH peeling increase ONH and retinal blood flow. Colorimetric and morphometric analyses offer valuable insights for future artificial intelligence and deep learning applications in this field., Translational Relevance: The methodology described herein can easily be applied in different clinical settings and may enlighten the beneficial effects of vitrectomy in several retinal vascular diseases.

Objective: This study investigates the effectiveness of demineralized bone matrix (DBX) to close alveolar clefts in patients previously treated with bone morphogenic protein-2 (BMP-2) who remained with bone nonunion., Design: This is an IRB-approved retrospective, single-center study., Setting: This study was conducted at a tertiary academic center., Patients/participants: We searched for all surgical encounters with the Current Procedural Terminology (CPT) code 42210 from the years 2013-2019. Included patients were diagnosed with cleft alveolus, previous BMP-2 exposure and required revision bone grafting during mixed dentition for persistent alveolar defects., Interventions: 17 patients underwent revision alveolar bone grafting (ABG) with either DBX (n = 10) or autograft (n = 7) to repair persistent bony cleft., Main Outcome Measure(s): The primary study outcome measured was alveolar bone graft revision failure described as continued alveolar nonunion., Results: The median age at revision ABG was 13.1 ± 3.3 years, with a mean follow-up time of 4.9 years (1.1-9.2 years). Patients were 53% male, 47% had a unilateral cleft lip and alveolus. 58.8% of patients were treated with DBX in the cleft, 41.2% treated with autograft from iliac crest. Overall, 11.8% (n = 2) of all revisions failed, requiring a second revision. The average time to reoperation was 2.06 years, and both were re-grafted with autograft. There was no statistically significant difference between the type of bone graft source used and the failure rate obtained ( P  = .1544)., Conclusions: DBX and autologous iliac crest bone grafts achieve similar alveolar union rates during revision ABG in patients treated with previous BMP-2 to the alveolar cleft., 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.

Transition of Care for Adolescents and Young Adults (AYA) with Neurogastroenterology & Motility (NGM) Disorders., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Competing Interests: J.B.H. receives book royalties from Elsevier. K.A.G. has no conflicts of interest to disclose.

Introduction: A growing number of Americans search online for health information related to urologic oncologic care each year. The American Medical Association recommends that medical information be written at a maximum sixth-grade level in order to be comprehensible by the majority of patients. As such, it is important to assess the quality and readability of online patient education material that patients are being exposed to., Methods: A Google search was performed using the terms "testicular cancer," "prostate cancer," "kidney cancer," and "bladder cancer," and the top 30 results for each were reviewed. Websites were categorized based on their source. Readability was assessed using the Flesch-Kincaid Grade Level, the Gunning Frequency of Gobbledygook, and the Simple Measure of Gobbledygook indices. Quality was assessed using the DISCERN Quality Index (1-5 scale)., Results: A total of 91 websites were included in our analysis. On average, online health information pertaining to urologic cancers is written at a 10th- to 11th-grade reading level, which is significantly higher than that of an average American adult and that recommended by the American Medical Association ( P < .01). The overall quality of websites was 3.4 ± 0.7, representing moderate to high quality. There was no significant difference in readability based on cancer type or information source., Conclusions: Despite being of moderate to high quality, online patient education materials related to common urologic cancers are often written at a grade level that exceeds the reading level of an average American adult. This presents as a barrier to online health literacy and calls into question the utility of these resources.

Background: Musculoskeletal (MSK) pathologies significantly affect the rehabilitation course for patients admitted to an inpatient rehabilitation facility (IRF). The impact of a specialized inpatient MSK consult service has not been previously evaluated., Objective: To assess the demographics, pathologies, and impact on pain scores of patients who were evaluated by a specialized MSK consult service., Design: Retrospective descriptive analysis of patients at an IRF who were evaluated by the MSK consult service., Setting: Academic IRF., Participants: 230 patients evaluated by the MSK consult service over 4.5 years., Interventions: MSK consult service composed of sports medicine fellowship-trained physiatrists who use history, physical examination, point-of-care ultrasound, and specialized MSK knowledge to assess and address MSK barriers to functional improvement., Main Outcome Measures: Primary rehabilitation diagnosis, length of stay, discharge destination, reason for consult, MSK diagnosis, need for injection, change in Numerical Pain Rating Scale (NPRS) pain scores, change in Functional Independence Measures (FIM)., Results: A total of 230 consults met inclusion criteria for analysis. The most common symptoms were shoulder pain (47%), knee pain (30%), and hip/groin pain (10.4%). The MSK consult service made 82 different musculoskeletal and neuromuscular diagnoses. The most common primary rehabilitation diagnosis was stroke (28.3%). Injections were performed in 44.3% of consults, with an average reduction in NPRS pain score of 2.3 (SD 1.9) and a statistically significant reduction in average NPRS pain scores in patients who underwent injections compared to those who did not (p < .001)., Conclusions: This study is the first to examine the use of an innovative inpatient MSK physiatry consult service in an IRF. This promising consult service can play a pivotal role in patient care by reducing functionally limiting MSK pain to allow for better toleration of therapies and to optimize functional gains., (© 2023 The Authors. PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

The human microbiota, a community of microorganisms in our bodies, is crucial for our health. This paper explores its development from birth through old age, highlighting some of the unique roles at key life stages-infancy, adulthood, and in the elderly years. Understanding the significant health impacts and consequences of changes in the microbiota offers insights for both the public and clinicians., Competing Interests: Disclosure: No financial disclosures reported. Artificial intelligence was not used in the study, research, preparation, or writing of this manuscript., (Copyright 2024 by the Missouri State Medical Association.)

The COVID-19 pandemic necessitated a rapid shift in clinical research to perform virtual visits and remote endpoint assessments, providing a key opportunity to optimize the use of remote endpoints for clinical trials in cystic fibrosis. The use of remote endpoints could allow more diverse participation in clinical trials while minimizing participant burden but must be robustly evaluated to ensure adequate performance and feasibility. In response, the Cystic Fibrosis Foundation convened the Remote Endpoint Task Force (Supplemental Table 1), a multidisciplinary group of CF researchers with remote endpoint expertise and community members tasked to better understand the current and future use of remote endpoints for clinical research. Here, we describe the current use of remote endpoints in CF clinical research, address key unanswered questions regarding their use and feasibility, and discuss the next steps to determine clinical trial readiness., Competing Interests: Declaration of competing interest Related to this work, MEJ reports employment by the Cystic Fibrosis Foundation (CFF). Unrelated to this work the authors report the following: DB reports consulting fees and stocks from Anagram Therapeutics Scientific Advisory Group and is a member of the Board of Directors for Anagram Therapeutics Scientific Advisory Group. CE reports honoraria for teaching presentations from Vertex and Chiesi. CHG reports grant funding from NIH NIDDK and NCRR, CFF, FDA Orphan Prod. Div. He received consulting fees from Enterprise Therapeutics and honoraria from Gilead and Vertex. He has received travel support from Vertex Pharmaceuticals and Enterprise Therapeutics. He participates on the DSMB for Novartis. He is a deputy editor for Annals of the ATS. He has stock in Air Therapeutics. GH reports grant funding from NIH NHLBI and CFF and support from CFCanada for travel. JEH reports grant funding from CFF and NIH, travel support from CF Canada, consulting fees from Vertex Pharmaceuticals and participation on an advisory board for Vertex Pharmaceuticals. DP reports grant funding from the CFF and consulting fees from Renexion Pharma. MSP reports grant funding from Dexcom Inc, CFF and Vertex Pharmaceuticals. She also reports consulting fees from Anagram Therapeutics and honoraria from Vertex Pharmaceuticals and TD Cowan. She is a member of the CFF DSMB and an associate editor for Endocrine Practice: Journal of the American Association of Clinical Endocrinologists. KAR reports grant funding from the CFF. MS reports grant funding from the CFF and Anagram Therapeutics. She has received consulting fees from Nestle International and Alcresta Therapeutics. She has received travel support from the CFF and serves on the CFF DSMB and reports a leadership role in the CFF. JS reports being a member of the CFF DSMB and advisory boards. ST reports honoraria from Vertex Pharmaceuticals. ETZ reports grant funding from CFF, NIH NHLBI, Vertex Pharmaceuticals. She has received consulting fees from CFF and Vertex Phamaceuticals and honoraria from the CFF and Asosciation for Diagnostic and Laboratory Medicine. She has received travel support from Vertex Pharmaceuticals, CFF and European Cystic Fibrosis Society. She has participated on advisory boards for CFF, CFF Therapeutics Development Network and Vertex Pharmaceuticals. MB, NL, KP and MR have no conflicts to report., (Copyright © 2024. Published by Elsevier B.V.)

While attention deficit hyperactivity disorder is common among people with addiction, the risks and benefits of attention deficit hyperactivity disorder medication in pregnant people with opioid use disorder are poorly understood. Here, using US multistate administrative data, we examined 3,247 pregnant people initiating opioid use disorder treatment, of whom 5% received psychostimulants. Compared to peers not receiving psychostimulants, the psychostimulant cohort had greater buprenorphine (adjusted relative risk 1.81 (1.50-2.18)) but lower methadone initiation (adjusted relative risk 0.39 (0.19-0.78)). Among psychostimulant recipients who initiated buprenorphine, we observed lower buprenorphine discontinuation associated with the psychostimulant cohort compared to nonrecipients (adjusted hazard ratio 0.77 (0.67-0.88)). In within-person case-crossover analyses, person-days defined by psychostimulant fills were associated with fewer substance use disorder-related admissions compared to days without fills (odds ratio 0.50 (0.33-0.76)). Overall, our data suggest that psychostimulant use in pregnancy may be associated with increased buprenorphine initiation, decreased methadone initiation and improved buprenorphine retention. Decreased substance use disorder-related admissions were associated with person-days of psychostimulant receipt, although other risks of psychostimulant use in pregnancy warrant further investigation., Competing Interests: R.A.G. reported receiving grants from the NIH and Arnold Ventures LLC during the conduct of the study, consulting for Janssen Pharmaceuticals and receiving personal fees for grant reviews from the NIH outside the submitted work. These funding sources had no influence on the design and analysis of the present study. The remaining authors declare no competing interests.

Competing Interests: Disclosure: No financial disclosures reported. Artificial intelligence was not used in the study, research, preparation, or writing of this manuscript.

Transverse myelitis (TM) is a frequently encountered inpatient neurological condition, usually with a broad differential of etiologies narrowed down by detailed history, temporal profile of symptom evolution, and pertinent diagnostic studies. We report a rare case of a 39-year-old man who presented with subacute onset of headaches and confusion, and three days later developed quadriplegia and areflexia. He was diagnosed with acute longitudinally extensive transverse myelitis (LETM) related to Epstein-Barr virus (EBV) superimposed on an initial presentation of streptococcal meningitis. As both etiologies are under-reported, we compare our case to the few similar cases in the literature to guide discussion of the clinical and radiologic findings of parainfectious TM related to EBV and streptococcal meningitis. Readers will have the challenge of attributing our patient's myelitis to one of these parainfectious sources and are encouraged to evaluate for rare infectious etiologies in acute settings., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Chronic venous insufficiency (CVI) is increasing in prevalence on a global scale. Current treatment options are limited to improving venous return, ablation of refluxing veins, and reducing outflow obstruction. A new bioprosthetic device, the VenoValve, may bridge the gap of treatment for patients with chronic venous insufficiency who have failed prior treatment. We demonstrate the treatment of a 72-year-old man with bilateral venous insufficiency and leg wounds using this device in his left femoral vein via an open anterior surgical approach. The patient had no postoperative complications, and a patent valve at 6 months. The VenoValve may be a viable option for patients with advanced chronic venous insufficiency., Competing Interests: None., (© 2024 The Author(s).)

Competing Interests: Outside the submitted work, S.M. reports receiving support for attending meetings and travel from Amgen and Sanofi Genzyme, and A.V. received honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Alexion. The remaining authors have no disclosures. The results presented in this letter have not been published previously in whole or part, except in abstract format.

Neuropsychiatric systemic lupus erythematosus (SLE) is a rare condition that has a multitude of mechanisms resulting in the emergence of variable clinical presentations. We describe a peculiar case of a 33-year-old female with a history of SLE presented with two weeks of fever, headache, and vomiting. On admission, she became obtunded and was emergently intubated. Initial lumbar puncture revealed pleocytosis (46% neutrophils, 320 corrected nucleated cells/μL), elevated protein (244 mg/dL; normal, 15-40 mg/dL), normal glucose (63 mg/dL), and negative cultures. Empiric acyclovir, ampicillin, ceftriaxone, and vancomycin were initiated without clinical improvement. Neurological examination was notable for limited ability to follow commands, vertical nystagmus, horizontal gaze palsy, diffuse hyperreflexia, and quadriparesis. Electroencephalogram (EEG) was consistent with diffuse encephalopathy. Brain magnetic resonance imaging demonstrated restricted diffusion and contrast enhancement in the posterior and central pons with edema. A cerebral angiogram showed no signs of vasculitis. Treatment with intravenous (IV) methylprednisolone 1 g and IV immunoglobulin 2 g/kg was initiated for five days. Despite these interventions, no discernible clinical improvement was observed, prompting the commencement of 500 mg/m 2  cyclophosphamide and daily maintenance of IV methylprednisolone at 2 mg/kg. A repeat MRI three weeks later revealed a marked reduction in the size of the lesion involving the pons. The patient also improved clinically over the month with successful extubation, complete return in mental capabilities, and the ability to ambulate short distances with assistance., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Polhemus et al.)

Purpose: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating neuromuscular and clinical outcomes of blood flow restriction (BFR) training after anterior cruciate ligament reconstruction (ACLR) compared with non-BFR rehabilitation protocols., Methods: A systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic reviews and Meta Analyses guidelines by querying PubMed, MEDLINE, Scopus, the Cochrane Database for Systematic Review, and the Cochrane Central Register for Controlled Trials databases from inception through December 2023 to identify Level I and II RCTs evaluating outcomes of BFR training after ACLR compared with non-BFR rehabilitation. A meta-analysis was performed using random-effects models with standardized mean difference (SMD) for pain, muscle strength, and muscle volume, whereas mean difference was calculated for patient-reported outcome measures., Results: Eight RCTs, consisting of 245 patients, met inclusion criteria, with 115 patients undergoing non-BFR rehabilitation compared with 130 patients undergoing BFR after ACLR. Mean patient age was 27.2 ± 6.7 years, with most patients being male (63.3%, n = 138/218). The length of the BFR rehabilitation protocol was most commonly between 8 and 12 weeks (range, 14 days to 16 weeks). Most studies set the limb/arterial occlusion pressure in the BFR group at 80%. When compared with non-BFR rehabilitation, BFR resulted in significant improvement in isokinetic muscle strength (SMD: 0.77, P = .02, I 2 : 58%), International Knee Documentation Committee score (mean difference: 10.97, P ≤ .00001, I 2 : 77%), and pain (SMD: 1.52, P = .04, I 2 : 87%), but not quadriceps muscle volume (SMD: 0.28, P = .43, I 2 : 76%)., Conclusions: The use of BFR after ACLR led to improvements in pain, International Knee Documentation Committee score, and isokinetic muscle strength, with variable outcomes on the basis of quadriceps strength, volume, and thickness when compared with non-BFR rehabilitation., Level of Evidence: Level II, systematic review and meta-analysis of Level I and II studies., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.M.K. has received support for education from Smith & Nephew, Elite Orthopedics, and Medwest Associates; hospitality payments from Arthrex, Encore Medical, Stryker, and Smith & Nephew; honoraria from Encore Medical; and a grant from Arthrex. All other authors (V.G., J.R.G., I.K.R., N.N.V., J.C.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Yao syndrome, a rare autoinflammatory disorder linked to mutations in the nucleotide-binding oligomerization domain-containing protein-2 (NOD2) gene, manifests through periodic fever, polyarthritis, dermatitis, gastrointestinal disturbances, and sicca-like symptoms. The therapeutic landscape is limited, primarily encompassing glucocorticoids, interleukin-1 (IL-1), and IL-6 inhibitors. This report details the case of a teenager with periodic fevers, arthritis, livedo reticularis, and NOD2 gene mutations R702W and IVS8+158C consistent with Yao syndrome. The individual demonstrated significant improvement with canakinumab therapy. This case report aims to enhance recognition and understanding of Yao syndrome's clinical spectrum and management options., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ahmad et al.)

Pyogenic arthritis, acne, pyoderma gangrenosum, and suppurative hidradenitis (PAPASH); pyogenic arthritis, pyoderma gangrenosum (PG), and acne; PG, acne, hidradenitis suppurativa; and PG, acne, spondylarthritis (PASS) are all part of a spectrum of autoinflammatory disorders that share similar pathogenesis. They are related to various mutations in the proline-serine-threonine phosphatase interacting protein 1, leading to dysregulation of the innate immune system and overproduction of interleukin (IL)-1, IL-17, and IL-23 and tumor necrosis factor (TNF)-α. Targeting these cytokines with biologics plays an important role in treatment. Here, we are describing the case of a young male with PAPASH syndrome who was treated with TNF-α and IL-1 inhibitor., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ahmad et al.)

Normal pressure hydrocephalus (NPH) is a syndrome that characteristically presents with progressive gait impairment, cognitive deficits, and urinary urgency or incontinence. We present a case of a 54-year-old male with a past medical history of alcohol use and no primary care provider with new-onset auditory hallucinations. The patient was found to have a marked enlargement of the supratentorial and infratentorial ventricles on both computed tomography (CT) and magnetic resonance imaging (MRI) and an opening pressure of 21 on the lumbar puncture, concerning for NPH. Clinically, there were signs of cognitive impairment due to memory and cognitive function loss, but the patient lacked gait disturbances or incontinence. Although not common, NPH may present with auditory hallucinations or delusions, as seen with our patient. In this case report, we emphasize the importance of annual cognitive assessments in order to evaluate atypical psychiatric manifestations of neurological disorders. Because clinical symptoms are more likely to be reversible when recognized early in the clinical course and the progression of these symptoms can be prevented with the placement of a ventriculoperitoneal (VP) shunt, it is of utmost importance to accurately recognize and diagnose NPH as early as possible. We also discuss the less commonly known markers of NPH on MRI., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rivkin et al.)

Background: Scrubs have become widespread office attire for plastic surgeons. The purpose of this study is to evaluate the public perception of scrub color and style for plastic surgeons., Methods: A crowdsourced survey was performed via MTurk. Respondents were asked to rate images of a surgeon dressed in black, navy, blue, and green scrubs as well as traditional or fitted scrubs. Qualities including representativeness, skill, trustworthiness, knowledge, and compassion were rated on a Likert scale across all images. Analysis of variance and one-sided t test were used to analyze differences in means., Results: In total, 562 responses were collected. For female plastic surgeons, navy and blue scrubs were perceived to be superior to those wearing black for skill, representativeness, trustworthiness, and compassion ( P < 0.05). For male plastic surgeons, navy and blue scrubs were superior to black for knowledge, skill, representativeness, trustworthiness, and compassion ( P < 0.05). For skill and representativeness, navy was superior to green ( P < 0.05). For representativeness, blue was superior to green ( P < 0.05). For trustworthiness and compassion, green was superior to black ( P < 0.05). Fitted scrubs were significantly preferred ( P < 0.05) across all characteristics with the exception of representativeness in the subgroup of male plastic surgeons., Conclusions: Black scrubs are associated with more negative characteristics than navy or blue scrubs, which were found to be the most positively perceived. Fitted scrubs were associated with positive characteristics for both male and female surgeons. The purchase of fitted scrubs may be a worthwhile purchase to maximize the patient-physician relationship., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Aim: To examine speed and accuracy of newborn heart rate measurement by various assessment methods employed at birth., Methods: A search of Medline, SCOPUS, CINAHL and Cochrane was conducted between January 1, 1946, to until August 16, 2023. (CRD 42021283364) Study selection was based on predetermined criteria. Reviewers independently extracted data, appraised risk of bias and assessed certainty of evidence., Results: Pulse oximetry is slower and less precise than ECG for heart rate assessment. Both auscultation and palpation are imprecise for heart rate assessment. Other devices such as digital stethoscope, Doppler ultrasound, an ECG device using dry electrodes incorporated in a belt, photoplethysmography and electromyography are studied in small numbers of newborns and data are not available for extremely preterm or bradycardic newborns receiving resuscitation. Digital stethoscope is fast and accurate. Doppler ultrasound and dry electrode ECG in a belt are fast, accurate and precise when compared to conventional ECG with gel adhesive electrodes., Limitations: Certainty of evidence was low or very low for most comparisons., Conclusion: If resources permit, ECG should be used for fast and accurate heart rate assessment at birth. Pulse oximetry and auscultation may be reasonable alternatives but have limitations. Digital stethoscope, doppler ultrasound and dry electrode ECG show promise but need further study., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Kapadia is a co-author of one of the studies included in this review. Drs. Liley and Rabi are editorial board members for the Resuscitation Plus journal. The other authors have no conflicts to disclose.’., (© 2024 The Author(s).)

Background: Treatment-seeking people with opioid use disorder (OUD) who are capable of pregnancy need accurate information about the potential impact of medication to treat OUD (MOUD) on fertility to make informed choices about treatment that are consistent with their reproductive wishes. There is a dearth of research on fertility associated with MOUD receipt in birthing people with OUD., Objective: To estimate the association between treatment with MOUD and odds of conception among birthing people using national administrative claims., Design: Retrospective case-crossover study using multi-state US administrative data (2006-2016). Dates of conception were estimated from delivery dates and served as "case" days for which MOUD exposures were compared to those on all other ("control") days of insurance enrollment., Participants: Treatment-seeking people with OUD with a delivery during the observation period., Main Measures: Odds ratios for conception from within-person fixed effects models were modeled as a function of exposure to MOUD (buprenorphine, methadone, extended-release depot naltrexone, or oral naltrexone) using conditional logistic regression., Key Results: A total of 21,928 births among 19,133 people with OUD were identified. In the sample, 5873 people received buprenorphine, 1825 methadone, 486 extended-release naltrexone, and 714 oral naltrexone. Participants could receive more than one type of MOUD. Mean age was 28.2 years (SD = 2.2; range = 16-45), with 76.2% having Medicaid. vs. commercial insurance. Compared to no MOUD, periods of methadone (aOR = 0.55 [95% CI = 0.48-0.63]) or buprenorphine receipt (aOR = 0.84 [0.77-0.91]) were associated with fewer conceptions. Treatment periods with extended-release depot naltrexone compared to no medication were associated with higher odds of conception (aOR = 1.75 [1.22-2.50]) and there was no significant difference in conception with oral naltrexone (aOR = 1.02 [0.67-1.54])., Conclusions: The association between MOUD and odds of conception among birthing people varied by type of MOUD, with extended-release naltrexone associated with higher odds of conceiving compared to no treatment. Clinical studies are urgently needed to investigate these findings further., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Introduction: Crossbow injuries are rare but carry significant morbidity and mortality, and there is limited evidence in the medical literature to guide care. This paper reviews the case reports and case series of crossbow injuries and looks for trends regarding morbidity and mortality based on the type of arrow, anatomic location of injury, and intent of injury., Methods: Multiple databases were searched for cases of crossbow injuries and data were abstracted into a spreadsheet. Statistics were done in SPSS., Results: 358 manuscripts were returned in the search. After deduplication and removal of nonclinical articles, 101 manuscripts remained. Seventy-one articles describing 90 incidents met the inclusion criteria. The mean age was 36.5 years. There were 10 female and 79 male victims. Fatality was 36% for injuries by field tip arrows and 71% for broadhead arrows, p   =  .024. Assaults were fatal in 84% of cases, suicides in 29%, and accidental injuries in 17%, p  < .001. Mortality was similar for wounds to the head and neck (41%), chest (42%), abdomen (33%), extremities (50%), and multiple regions, p   =  .618., Conclusions: Crossbows are potentially lethal weapons sold with fewer restrictions than firearms. Injuries caused by broadhead arrows are more likely to be fatal than injuries from field tip arrows. The anatomic location of injury does not correlate with fatality. More than half of crossbow injuries are due to attempted suicide, with a high case-fatality rate.

Several known factors affect outcomes of Mohs facial defect reconstruction; however, the effect of repair timing on outcomes is ill-defined. The aim of this study was to determine postoperative complication rates between immediate and delayed repair of Mohs facial defects. Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines were used. Articles were selected using PICO format-population: Mohs facial defect patients, intervention: defect repair, comparator: immediate (<24 hours), or delayed (>24 hours) repair, outcome: complication rate. PubMed/Medline (1946-2020), EMBASE (1947-2020), Scopus (1823-2020), Web of Science (1900-2020), Cochrane Library, and Clinicaltrials.gov were searched. Two independent reviewers screened abstracts; those in English with human subjects reporting repair timing and complication rates were included. Search criteria yielded 6,649 abstracts; 233 qualified for review. Data were gathered from six studies; they alone contained comparative data meeting inclusion criteria. While many well-written studies were encountered, reported results varied widely. A statistically sound meta-analysis could not be completed due to large heterogeneity between studies, biasing the analysis towards the largest weighted study. Clinically important differences may exist between immediate and delayed Mohs reconstruction, but small study numbers, large heterogeneity, and lack of standardized outcome measures limit definitive conclusions. More studies are needed to perform appropriate meta-analyses, including studies using standardized methods of reporting Mohs outcome data., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: Neuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care., Observations: Consensus definitions have evolved for psychosis, agitation, apathy, depression, and disinhibition in NDDs. Psychosocial interventions may reduce mild behavioral symptoms in patients with NDD, and pharmacotherapy is available for NPSs in NDDs. Brexpiprazole is approved for treatment of agitation associated with Alzheimer disease dementia, and pimavanserin is approved for treatment of delusions and hallucinations associated with psychosis of Parkinson disease. Trials are being conducted across several of the NDDs, and a variety of mechanisms of action are being assessed for their effect on NPSs., Conclusions and Relevance: Detection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.

Oral calorie intake causes an acute and transient decline in serum testosterone concentrations. It is not known whether this decline occurs in men on testosterone therapy. In this study, we evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy. This is a secondary analysis of samples previously collected from a study of hypogonadal men with type 2 diabetes who received testosterone therapy. Study participants (n = 14) ingested 75 grams of oral glucose, and blood samples were collected over 2 h. The test was repeated after 23 weeks of intramuscular testosterone therapy. The mean age and body mass index of study volunteers were 53 ± 8 years and 38 ± 7 kg/m 2 , respectively. Following glucose intake, testosterone concentrations fell significantly prior to testosterone therapy (week 0, p = 0.04). The nadir of testosterone concentration was at 1 h, followed by recovery to baseline by 2 h. In contrast, there was no change in testosterone concentrations at week 23. The change in serum testosterone concentrations at 60 min was significantly more at week 0 than week 23 (-11 ± 10% vs 0 ± 16%, p = 0.05). We conclude that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for the diagnosis of hypogonadism, but not for monitoring testosterone therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Dhindsa has received honoraria from Bayer, Acerus Pharmaceuticals and Marius pharmaceuticals, and research support from Clarus Therapeutics. Dr. Dandona has received honoraria from Eli Lilly, Novartis, GlaxoSmithKline, Merck, Novo Nordisk, Takeda and Sanofi- Aventis, and research support from National Institutes of Health, JDRF, ADA, Novo Nordisk, Bristol Meyer Squibb, AbbVie Pharmaceuticals, Astra Zeneca and Boehringer Ingelheim Pharmaceuticals. These interests are not related to and did not influence the current study. All other authors declare no competing financial interests.

Introduction: Cholinesterase inhibitors, along with memantine, are the mainstay of symptomatic treatment for AD (Alzheimer's disease); however, these medications are typically administered orally, which can be difficult for people with AD and their caregivers., Areas Covered: In this drug profile and narrative review, the authors trace the development of the new FDA-approved transdermal donepezil. The authors discuss the studies showing its bioequivalence with the oral formulation, including two double-blinded placebo controlled non-inferiority trials. The authors also compare the patch to the only other transdermal cholinesterase inhibitor on the market, rivastigmine, and highlight the potential advantages and disadvantages between these two treatments., Expert Opinion: While the patch is bio-equivalent, it is rather large and may not be affordable for some patients. In addition, there is no high dose (e.g. 23 mg) equivalent. Nevertheless, transdermal donepezil will be useful for people with AD and their caregivers, given its effectiveness and potential convenience.

Background: Due to the importance of evidence-based research in plastic surgery, the authors of this study aimed to assess the accuracy of ChatGPT in generating novel systematic review ideas within the field of craniofacial surgery., Methods: ChatGPT was prompted to generate 20 novel systematic review ideas for 10 different subcategories within the field of craniofacial surgery. For each topic, the chatbot was told to give 10 "general" and 10 "specific" ideas that were related to the concept. In order to determine the accuracy of ChatGPT, a literature review was conducted using PubMed, CINAHL, Embase, and Cochrane., Results: In total, 200 total systematic review research ideas were generated by ChatGPT. We found that the algorithm had an overall 57.5% accuracy at identifying novel systematic review ideas. ChatGPT was found to be 39% accurate for general topics and 76% accurate for specific topics., Conclusion: Craniofacial surgeons should use ChatGPT as a tool. We found that ChatGPT provided more precise answers with specific research questions than with general questions and helped narrow down the search scope, leading to a more relevant and accurate response. Beyond research purposes, ChatGPT can augment patient consultations, improve healthcare equity, and assist in clinical decisionmaking. With rapid advancements in artificial intelligence (AI), it is important for plastic surgeons to consider using AI in their clinical practice to improve patient-centered outcomes.