Citations

Objectives: Determine whether the timing of transplantation affects patient mortality. Background: Neoadjuvant therapy and liver transplantation have emerged as an excellent treatment option for select patients with perihilar cholangiocarcinoma (pCCA). However, the optimal timing of transplantation is not known. Methods: We reviewed all patients registered for a standardized pCCA protocol between 1996 and 2020 at our center. After adjusting for confounders, we examined the association of waiting time with patient mortality in an intention-to-treat cohort (n=392) and those who received a liver transplant (n=256). Results: The median (interquartile range) time from registration to transplant or dropout was 5.74 (3.25–7.06) months. Compared with a short wait time (0–3 mo), longer waiting times did not affect all-cause mortality: (3–6 mo) hazard ratio (HR) 0.98; 95% CI: 0.52–1.84; (6–9 mo) HR: 0.80; 95% CI: 0.39–1.65; (9–12 mo) HR: 0.56; 95% CI: 0.26–1.22. Subgroups with a shorter waiting time had similar survival to those with long waiting times: living donor available HR: 0.97; 95% CI: 0.67–1.42; AB or B blood group HR: 0.93; 95% CI: 0.62–1.39. Longer waiting times were associated with decreased all-cause mortality after transplantation (HR: 0.92; 95% CI: 0.87–0.97). This benefit began after a 6-month waiting time minimum (HR: 0.53; 95% CI: 0.26–1.10) and increased further after 9 months (HR: 0.43 95% CI: 0.20–0.93). Waiting time was not associated with residual adenocarcinoma in the explant (odds ratio 0.99; 95% CI: 0.98–1.00). Conclusions: A waiting time of at least 6 months will optimize results with transplantation without affecting overall (intention-to-treat) patient survival.

AbstractObjectiveCritical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies.Study DesignA consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations.SettingAn online questionnaire was distributed in July 2023.MethodsThe questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W‐NASs) to represent the perceived importance of each feature, scaled from 0 to 1.ResultsGeneral concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W‐NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W‐NAS, 0.67). Similar analyses were performed for features in each case.ConclusionThe implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision‐making during nasal endoscopy.

Abstract Sex and gender—biological and social constructs—significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex‐ and gender‐specific drivers of resilience, including a sex/gender‐oriented review of risk factors, genetics, AD and non‐AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender‐aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender‐specific resilience throughout disease stages. Highlights Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex‐specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex‐specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

AbstractPediatric procedure‐related pain management is often incompletely understood, inadequately addressed, and critical in influencing a child's lifelong relationship with the larger healthcare community. We present a comprehensive review of infiltrative anesthetics, including a comparison of their mechanisms of action and relative safety and efficacy data to help guide clinical selection. We also describe the multimodal utilization of adjunct therapies—in series and in parallel—to support the optimization of pediatric periprocedural pain management, enhance the patient experience, and provide alternatives to sedation medication and general anesthesia.

AbstractA 44‐year‐old male presented with a 2‐month history of erythematous ulcerative papules and plaques on the scalp, face, and bilateral lower legs. He had a 5‐year history of well‐controlled HIV on antiretroviral therapy and recurrent syphilis infections. His face had violaceous plaques, while bilateral ankles and calves had ulcerative lesions with necrotic centers and purple borders. The morphologies clinically mimicked pyoderma gangrenosum on the lower extremities and cutaneous lymphoma on the face. Biopsy and reactive rapid plasma reagin confirmed a diagnosis of lues maligna, and the patient was successfully treated with penicillin G benzathine.

AbstractYao syndrome (YAOS) is a novel systemic autoinflammatory disease linked to the nucleotide‐binding oligomerization domain (NOD2) gene. It is characterized by periodic fevers, gastrointestinal (GI) symptoms, arthritis, and dermatitis, among other symptoms. A sparse literature exists on this disease, and little is known about its dermatological manifestations. A review of available literature was performed to characterize the cutaneous manifestations of Yao syndrome. Cutaneous manifestations were documented in 85.7% of patients, with common characteristic descriptions of erythematous patches and plaques involving the face, trunk, abdomen, and extremities. Based on our review of treatment modalities employed for Yao syndrome, prednisone is an appropriate initial approach, with oral sulfasalazine and other disease‐modifying antirheumatic drugs serving as appropriate secondary options. YAOS should be considered in the differential diagnosis of patients presenting with a dermatitic rash, especially in the context of concurrent articular symptoms, periodic fever, and GI symptoms.

Myocarditis is defined by an immune response to infection or injury, most commonly identified after a viral infection or recent exposure to cardiotoxins or drugs. Classic myocarditis may also result from the activation of the immune system by self-antigens without an exogenous trigger. Pathogenic variants of genes encoding sarcolemmal and desmosomal proteins are present in 4% to 44% of myocarditis patients and may relate to persistent cardiac dysfunction and arrhythmias. The most common clinical presentation is acute chest pain resembling an ischemic infarction or pericarditis. Heart failure and syncope from tachy- or brady-arrhythmias are features of a complicated clinical course with substantial risk of future cardiovascular events and death. High-sensitivity troponin, ECG, and echocardiograms are useful but lack sufficient sensitivity and specificity to confirm the diagnosis. Cardiovascular magnetic resonance is indicated to confirm myocarditis in low-risk, uncomplicated cases. Endomyocardial biopsy is indicated to guide therapy in high-risk scenarios. In this review, we discuss the clinical aspects, pathogenesis, genetic susceptibility, and management of uncomplicated, complicated, and fulminant myocarditis related to viral injury. We identify gaps in understanding and suggest prime research questions in the pathogenesis, diagnosis, and treatment of acute myocarditis. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05335928.

AbstractKnee osteoarthritis (KOA) significantly contributes to the global disability burden, with its incidence expected to escalate by 74.9% by 2050. The urgency to comprehend and tackle this condition is critical, necessitating an updated and thorough review of KOA. A systematic review up to February 26, 2024, has elucidated the principal aspects of KOA's pathogenesis, risk factors, clinical manifestations, and contemporary management paradigms. The origins of KOA are intricately linked to mechanical, inflammatory, and metabolic disturbances that impair joint function. Notable risk factors include age, obesity, and previous knee injuries. Diagnosis predominantly relies on clinical assessment, with radiographic evaluation reserved conditionally. The significance of rehabilitation assessments, informed by the International Classification of Functioning, Disability, and Health framework, is highlighted. Treatment strategies are diverse, prioritizing nonpharmacological measures such as patient education, exercise, and weight management, with pharmacological interventions considered adjuncts. Intra‐articular injections and surgical options are contemplated for instances where conventional management is inadequate. KOA stands as a predominant disability cause globally, characterized by a complex etiology and profound effects on individuals’ quality of life. Early, proactive management focusing on nonpharmacological interventions forms the cornerstone of treatment, aiming to alleviate symptoms and enhance joint function. This comprehensive review underscores the need for early diagnosis, individualized treatment plans, and the integration of rehabilitation assessments to optimize patient outcomes. Further research is needed to refine prevention strategies and improve management outcomes for KOA patients.