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ABSTRACTBackgroundRenal medullary carcinoma (RMC) is an aggressive tumor associated with sickle cell trait. Despite treatment advances for other rare renal tumors, RMC survival remains poor. We aimed to describe the contemporary management and survival of children and adults with RMC.ProcedureIn this multicenter retrospective cohort study, Pediatric Surgical Oncology Research Collaborative sites searched their databases for patients diagnosed with RMC (2000–2022). Descriptive statistics were calculated and survival analyses performed using Kaplan–Meier and Cox regression.ResultsThirty‐four patients with RMC were identified. Median age was 19 years (IQR: 15–28; range: 7–52). Most were male (24/34; 71%), Black (27/32; 84%), had sickle cell trait or disease (30/33; 91%), presented with metastatic disease (27/34; 79%), and were symptomatic at presentation (32/34; 94%). Median overall survival (OS) was 24 months from diagnosis (16 months for children, 28 months for adults, p = 0.6). Receipt of platinum‐based chemotherapy (23/34; 68%) was associated with significantly higher OS than other regimens (35 vs. 5 months, p < 0.001). Nephrectomy (24/34; 71%) was associated with significantly improved OS compared with non‐operative management (34 vs. 7 months, p = 0.001). Immunotherapy, targeted therapy, or radiation therapy were not associated with significant differences in OS, nor were age, sex, race, sickle cell status, SMARCB1/INI‐1, stage, nephrectomy approach, retroperitoneal lymph node dissection, gross residual disease, margins, or tumor size.ConclusionsRMC survival remains poor despite newer therapies. Nephrectomy and platinum‐based chemotherapy should be considered in locally advanced and metastatic disease. Coordinated international cooperative group studies are needed to meaningfully improve RMC survival.

Abstract Rationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary condition characterised by neuroendocrine cell proliferation along respiratory bronchioles resulting in tumourlet formation which may progress to pulmonary carcinoid. DIPNECH is a rare and under-recognised condition that predominantly affects females, with an estimated worldwide incidence of 5-6 people per million population. Given it's rarity and the poor understanding around the pathogenesis and treatment of this condition, we undertook the largest international case series to date of DIPNECH patients. We aim to further characterise this patient cohort to better understand the clinical features, identify common pulmonary function test (PFT) patterns and radiographic findings and describe current treatment practices. Methods: We collated data from 17 centres across 8 different countries comprising a total of 258 patients. Data collected included patient demographics, smoking history, symptoms, co-morbidities, pathological diagnosis, imaging findings, PFT pattern and therapies. Results: In total 258 patients were identified. The median age was 65 (SD+/- 10.6). 241 (93%) were female. 39% (n= 94/243) were ex-smokers. 79% (n=186/234) of patients reported pulmonary symptoms with cough being the most common symptom reported in 81% (n=151/186) of patients. Many patients were polysymptomatic, with cough and dyspnoea being the most common combination of symptoms described. (50.54%; n=94/186). Complete spirometry pattern was documented for 180 patients (69.78%) with an obstructive pattern being the most commonly observed (n=76/180; 42%). 27.5% (n=41/139) had clinically significant FEV1 reversibility post bronchodilator administration. Pathology specimens were available in 219 cases. Most common pathological features were neuroendocrine hyperplasia which was observed in 75% (n=165/219) and tumourlets in 74% (n=162/219) of cases. Carcinoid, either typical or atypical, was observed in 64% (n=141/219) of samples. 252 patients had computed tomography (CT) imaging performed. Pulmonary nodules were the most common feature identified in 99.60% of cases (248/250). Mosaic attenuation (69.30%; n=50/173) and airway dilatation (28.90%; n=50/173) were also frequently reported. There was no significant correlation between symptoms (cough, dyspnoea, wheeze) and airway dilatation (p=0.496), mosaic attenuation (p=0.496) and PFT pattern (p=0.837). There was a significant association between presence of symptoms and mosaic attenuation on CT (p=0.003). Conclusions: DIPNECH, while a rare disorder, is understudied. This international case series is the largest performed to date and highlights the complexity in management of these patients.

Abstract An individual participant data (IPD) meta-analysis can assess the predictive value of data on outcomes at the individual level, offering a potential tool for developing personalized pain management. Pretreatment quantitative sensory testing (QST) may stratify patient groups, which are then linked to treatment outcomes. Our objective was to determine if measures of QST at baseline are related to treatment outcomes (at any time point) for pain and disability in lower-limb osteoarthritis. We performed a systematic review with an IPD meta-analysis. Searches were conducted in 9 databases until May 5, 2023 for intervention studies that measured baseline QST and longitudinal measures of participant-reported pain and disability. We performed a 2-stage approach to analyse longitudinal data. Individual models were fitted to each study and combined using random effects multivariate meta-analytic models. Study quality was assessed using the Joanna Briggs Institute checklist, and certainty of the evidence was assessed using GRADE. We identified 3082 records and included 1 hip and 28 knee datasets consisting of 2522 participants from 40 studies. Local warm detection thresholds (P = 0.024) predicted knee osteoarthritis pain outcomes (very-low certainty). Local warm detection thresholds (P = 0.030), remote cold detection thresholds (P = 0.05), and remote pressure tolerance thresholds (P = 0.007) predicted knee osteoarthritis disability outcomes (very-low certainty). Other QST variables were associated with hip and knee osteoarthritis pain and disability levels (eg, pressure pain thresholds), but this relationship did not change over time. This review finds that mechanism-based, QST methodologies do not consistently predict pain or disability on an individual level in hip or knee osteoarthritis.

ABSTRACTLung transplantation is indicated for selected patients with advanced pulmonary arterial hypertension (PAH). We used a modified Delphi process to develop recommendations on care of patients with PAH undergoing lung transplantation. This Delphi panel was recruited from the Pulmonary Vascular Research Institute's Innovative Drug Discovery Initiative ‐ Lung Transplantation Workstream, consisting of clinical and research experts in PAH and lung transplantation. In this process, 29 panelists were given open‐ended questions, querying topics related to lung transplantation in PAH. A steering group converted the responses into discrete statements. Panelists then rated agreement using a Likert scale in two further survey rounds: −5 (strongly disagree) to 5 (strongly agree). Consensus was defined as mean ≥ 2.5 or ≤ −2.5, with a standard deviation not crossing zero. Consensus was reached on 141 of 223 statements. Notable areas of consensus were for early discussions about transplantation, and agreement with previously published referral and listing criteria. There was agreement that lung transplantation could be offered in sick candidates, including those with concurrent renal or hepatic insufficiency. Bilateral lung transplantation was considered the procedure of choice for most patients, with rare indications for heart‐lung transplantation. Consensus on bridging strategies included use of veno‐arterial extracorporeal membrane oxygenation and preemptive awake cannulation in those with severe right ventricular dysfunction. Consensus was also achieved on intraoperative use of invasive hemodynamic monitoring, and prolonged postoperative circulatory support guided by hemodynamic response and echocardiography. Patients with PAH undergoing transplantation require specialized management, which differs somewhat from other candidates.

Objective: Review the current literature for available treatments for acute cholecystitis (AC) in nonsurgical candidates and provide guidelines for the management of these patients. Background: Cholecystectomy is the gold-standard treatment modality for AC. A considerable number of patients who are not eligible for surgery are managed by percutaneous and endoscopic techniques. There is recent data regarding endoscopic ultrasound-guided gallbladder drainage and emerging percutaneous approaches to address cholelithiasis and remove drains. Methods: An expert panel of surgeons, gastroenterologists, and interventional radiologists reviewed the current literature and provided recommendations for AC management in nonsurgical candidates. Recommendations were based on relevant evidence, with quality and strength assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Percutaneous cholecystostomy is advised for patients ineligible for lumen-apposing metal stent (LAMS) or with reversible conditions, aiming to bridge to cholecystectomy. The optimal timing of cholecystectomy after percutaneous cholecystostomy remains unclear. In cases where surgery is not feasible, potential definitive treatments such as percutaneous cholecystolithotripsy/lithectomy and cholecystoduodenal stenting should be considered. For calculous AC, endoscopic ultrasound-guided gallbladder drainage with LAMS is recommended as a therapy for never-surgical candidates if they are eligible for monitored anesthesia care or general anesthesia and there is institutional expertise and minimal intervening ascites. Conclusions: The management of AC in nonsurgical candidates remains a challenge, with institutional protocols varying based on physician preferences and expertise. The proposed protocol integrates percutaneous and endoscopic approaches and emphasizes the need for multidisciplinary collaboration. Further research is required to evaluate these evolving management techniques, as the current literature is limited.

ABSTRACT Background Hospital at home (HaH) provides hospital‐level care at home as a substitute for brick‐and‐mortar hospital care. Multiple HaH studies demonstrate HaH provides safe, high‐quality, cost‐effective care. However, practices have varied approaches to delivering care and no HaH‐specific national standards exist. We aimed to develop national practice standards for HaH and assess practice performance against the standards. Methods The HaH Users Group (HaHUG), the national convener of HaH practices, assembled the Practice Standards Council in 2019 to develop evidence‐based standards for HaH. We reviewed existing international standards and the requirements of the Centers for Medicare and Medicaid Services Acute Hospital Care at Home Waiver. We engaged in multiple iterative rounds to develop domains and standards within each domain and then held an open comment period. We distributed an online survey for all HaHUG practices to self‐assess whether they did not meet (score, −1), met (score, 0), or exceeded (score, +1) each standard. The American Hospital Association's Annual Survey was used to describe practices that did and did not complete the practice standards survey. Results Final practice standards included 31 standards in 7 domains: leadership; education and training; human resources management; quality and quality improvement; safe practice and environment; and clinical standards and protocols. The majority of HaH practices self‐rated that they met or exceeded standards: scores ranged from −5 to 31; mean score of 9.75 (SD, 12.60). Forty‐nine of 213 eligible HaH practices completed the survey (response rate, 23.0%). Most hospitals were large (65% > 299 beds), nonprofit (85%), teaching (90%) centers that cared for a large proportion of patients with Medicaid. Conclusion We present the first national practice standards for HaH. The vast majority of HaH practices met or exceeded these standards by their own assessment. There was a range of performance across standards, demonstrating strengths and opportunities for ongoing development and quality improvement.

Abstract Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as “lineage drift” were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of &lt;40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.

ImportanceDirect immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings.ObjectiveTo assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US.Design, Setting, and ParticipantsUsing modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution–based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024.Main Outcomes and MeasuresThe primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication.ResultsA total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys.Conclusions and RelevanceOverall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.