Citations

Objectives On rare occasions, hiccups can cause morbidity, such as sleep deprivation, aspiration and even death. At times, palliative invasive procedures are considered. This study tested the hypothesis that invasive procedures can provide hiccup palliation with an acceptable safety profile. Methods Multi-site electronic medical data were used to assess adult patients who underwent an invasive procedure for hiccups between January 1995 and January 2022. Hiccup palliation was defined as documented improvement in severity or frequency of this sign/symptom after the procedure. Results A total of 69 patients underwent one or more invasive procedures for hiccups (144 total procedures). Fifty-nine patients (86%) were men. The most frequent initial procedure was a phrenic nerve block (n=10) followed by oesophageal dilation (n=9). Only 31 patients (45%) manifested hiccup palliation after their first procedure. Nearly half, or 32 patients (46%), underwent more than one procedure (2 underwent nine procedures). Of these subsequent procedures, 35 resulted in palliation. Five adverse events arose from 144 procedures: post-esophagectomy atrial fibrillation, haematoma after cardiac device removal, vocal cord immobility after craniotomy, vocal cord immobility after vagal nerve manipulation, and a cerebral spinal leak after vagal nerve decompression. Conclusions Invasive procedures can palliate hiccups with an acceptable safety profile. However, these procedures appear to palliate hiccups in only about half of patients and sometimes do so only transiently.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs) can cause radiation-induced changes (RIC), but its interactions with AVM embolization are not well established. The aim of this study was to assess the effect of previous embolization on RIC in SRS-treated AVM patients. METHODS: Data of AVM patients treated with single-session SRS from 1987 to 2018 were retrieved from the International Radiosurgery Research Foundation. Univariable and stepwise backward logistic regression models were used to identify RIC predictors. Patients were stratified into those who received pre-SRS embolization (E + SRS) vs those who did not (SRS-only). Radiologic RIC (rRIC) was the primary end point. Secondary outcomes included symptomatic RIC (sRIC) and permanent symptomatic RIC (pRIC). RESULTS: Among 1187 AVM patients, the mean age was 36.4 years (SD 16.8), with 50.4% female patients. AVMs had a mean untreated AVM volume of 5.2 cm 3 . A total of 130 patients (11%) underwent neoadjuvant embolization (E + SRS). The overall rRIC and sRIC rates were 32.8% and 12.1%, respectively, with time to rRIC and sRIC being significantly longer in the E + SRS vs SRS-only cohorts (103.6 ± 339.4 vs 11.3 ± 12.5 and 60.4 ± 262.9 vs 9.5 ± 9.0 months, respectively). Seizures at presentation and ≥3-cm untreated AVM volume significantly correlated with a higher likelihood of rRIC (adjusted odds ratio [aOR] 2.32 [1.25-4.30] and aOR 2.77 [1.24-6.16], respectively). Age and pre-SRS embolization were associated with a significantly lower risk of rRIC (aOR 0.97 [0.96-0.99] and aOR 0.32 [0.13-0.74], respectively). The E + SRS cohort had significantly reduced odds of rRIC (aOR = 0.37 [0.15-0.89]) and pRIC (aOR = 0.04 [0.00-0.30]) after adjusting for significant covariates. CONCLUSION: Seizures at presentation and larger untreated AVM volume were independently associated with an increased risk of rRIC, whereas older age and pre-SRS embolization were protective. Notably, patients who underwent embolization before SRS had lower odds of rRIC and pRIC, with delayed onset of complications compared with SRS-only.

PURPOSE To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

Background. Long-term outcomes in kidney transplantation remain suboptimal, with subclinical acute rejection (subAR) frequently going undetected by conventional methods. We hypothesized that subAR represents a molecular precursor to clinical acute rejection (cAR). Leveraging a large National Institutes of Health-funded cohort with matched kidney tissue and peripheral blood samples, our primary objective was to determine whether subAR and cAR share molecular patterns, establishing subAR as an early stage of cAR. As a secondary aim, we compared biopsy and blood gene expression profiles to identify unique and shared pathways and to assess their diagnostic utility. Methods. This was a retrospective analysis of gene expression data from an observational clinical trial. We analyzed 578 blood and biopsy samples from 129 kidney transplant recipients enrolled in a multicenter observational study. Gene expression differences were analyzed using ANOVA with false discovery rate correction and molecular pathways analysis. Samples were matched and classified based on histologic findings and blood-based molecular diagnostics. Results. Gene expression and pathway analyses revealed that subAR exhibits a molecular profile consistent with a milder form of clinical rejection in both tissue and blood. Molecular signatures distinguished immune-mediated injury from nonimmune injury. Notably, tissue gene expression profiling in cases that were misclassified by peripheral blood diagnostics were like correctly classified cases, suggesting that histology alone may not reliably define true clinical phenotypes. Conclusions. Molecular profiling of tissue and blood reflects distinct but complementary aspects of transplant biology and confirms that subAR and cAR share overlapping molecular profiles, supporting the hypothesis that subAR represents an early stage in the progression toward clinical rejection. These findings highlight the limitations of relying solely on histological evaluation and support the use of molecular tissue profiling as an adjunct to histology, particularly in diagnostically ambiguous cases. Molecular profiling provides a supporting framework for identifying subclinical rejection and guiding personalized immunosuppression to improve long-term outcomes.

Autosomal dominant polycystic kidney disease is the most common inherited kidney disorder and a leading monogenic cause of kidney failure. Reduction or loss of polycystin-1 and polycystin-2 function disrupts ciliary calcium signaling, elevates cyclic AMP (cAMP), reprograms cellular metabolism, and activates proliferative cascades that drive cyst expansion. Tolvaptan, a vasopressin V2 receptor antagonist, established cAMP modulation as a disease-modifying strategy but is limited by aquaretic effects and hepatotoxicity risk. This review highlights emerging therapeutic strategies in clinical trial development that extend beyond vasopressin antagonism. Gene-directed therapies aim to restore polycystin dosage, including anti–miR-17 oligonucleotides ( e.g ., farabursen) and pharmacochaperones that rescue misfolded polycystin-1 and restore trafficking in select PKD1 missense variants ( e.g ., VX-407). Paracrine signaling can be modulated with anti–pregnancy-associated plasma protein A antibodies that reduce insulin-like growth factor-1 bioavailability in cystic microenvironments. Metabolic reprogramming is targeted by agents such as metformin, bempedoic acid, glucagon-like peptide-1 receptor agonists, and structured dietary interventions. Sodium-glucose cotransporter 2 inhibitors hold theoretical promise but await definitive results from ongoing trials. A novel cAMP-lowering strategy through phosphodiesterase-4 activation is advancing toward clinical testing. Looking ahead, gene therapy, and genome editing offer the potential to raise polycystin levels above the threshold for cystogenesis, although challenges in vector capacity, kidney-specific delivery, and durability remain. Artificial intelligence–guided discovery, coupled with human organoid platforms, is accelerating therapeutic repurposing and rational combination design. Collectively, these advances signal a transition toward a layered, mechanism-guided framework in which vasopressin blockade is integrated with metabolic, other signaling, and genotype-specific therapies. As biomarkers and risk stratification tools mature, autosomal dominant polycystic kidney disease management is poised to become increasingly precise, tolerable, and effective.

Objectives: In the United States, training for physicians who manage critically ill adult patients (intensivists) evolved through parallel subspecialty critical care medicine (CCM) pathways with significant commonality. The Society of Critical Care Medicine Adult Critical Care Physician Core Knowledge and Skills Task Force aimed to delineate the common core knowledge and skills required of all intensivists. Design: A master list of content areas and procedural skills was compiled from all CCM subspecialty program requirements and blueprints of the certification examinations. Using a modified Delphi approach, participants were asked to categorize the knowledge items as “advanced knowledge is essential,” “general, but not advanced, knowledge is essential,” or “knowledge is not essential.” Procedures were categorized as “intensivist performs routinely,” “intensivist only performs in an emergency,” or “intensivist knows” about the procedure. Setting: Representatives from CCM stakeholder organizations, including accreditation and certification organizations, critical care societies, and program directors’ societies, were invited to participate. SUBJECTS: Members of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care Medicine. Interventions: For the first two rounds of the modified Delphi process, Research Electronic Data Capture was used. For the third and fourth rounds, the process was completed through online meetings with Zoom (Zoom Video Corporations, San Jose, CA) utilizing Zoom’s polling feature. Measurements and Main Results: A total of 541 items were determined to be essential, with 145 requiring advanced knowledge and 323 requiring general knowledge. For 73 items, consensus regarding advanced vs. general could not be achieved, but they remained essential. Only eight items were felt to be nonessential. Of the 16 procedures, most were categorized as “intensivist performs.” Conclusions: The large number of items included in the list of essential knowledge and skills demonstrates the complexity of modern CCM. Utilization of a common framework across the subspecialties of CCM could lead to greater harmonization among the fellowship program requirements and certification examinations.

BACKGROUND: Guidelines recommend 3-hour cardiac amyloid radionuclide imaging (CARI) for transthyretin amyloid cardiomyopathy. Citing rapid blood clearance of 99m Tc-hydroxymethylene-diphosphonate (HMDP) and efficient laboratory throughput, 1-hour imaging is increasingly practiced despite limited supporting evidence. We sought to compare diagnostic performance and interpreter experience of 1-hour versus 3-hour HMDP-CARI. METHODS: Consecutive patients with suspected transthyretin amyloid cardiomyopathy (n=114) underwent both 1-hour and 3-hour HMDP single photon emission computed tomography (CT)/CT. Two cardiologist-radiologist reader teams, blinded to imaging timepoint (1 versus 3 hours), assessed overall interpretation, single photon emission CT–based Perugini grade, interpretation difficulty, interpreter confidence, and need for CT-fused images for anatomic localization. Discordant, equivocal, and difficult cases were arbitrated by a third tie-breaking team. The myocardial-to-blood-pool radiotracer uptake ratio (3-dimensional Score) was measured as a surrogate of contrast resolution. RESULTS: Interinterpreter agreement was high at both time points (κ≥0.81), with more cases requiring arbitration at 3 hours versus 1 hour (22% versus 13%; P =0.049). Overall interpretation and Perugini grades were concordant between time points in 111/114 (97%) and 106/114 (93%) patients, respectively. Three patients (3%) were negative at 1 hour but equivocal at 3 hours, all of which were clinically ruled out for transthyretin amyloid cardiomyopathy. Interpreter confidence was comparable at both timepoints (97% versus 95%; P =0.317). Compared with 3-hour imaging, contrast resolution was inferior (lower 3-dimensional score, P <0.001) and CT fusion was more frequently needed (57% versus 31%, P <0.001) at 1-hour imaging. CONCLUSIONS: In a prospective, blinded comparison of 1-hour versus 3-hour HMDP-CARI, diagnostic performance and interpreter experience were similar, with readers requesting CT fusion more frequently at 1 hour to optimize myocardial-to-blood pool discrimination.

ABSTRACT Background Older adults are at high risk for severe injuries and death from falls. Physical therapist (PT) and occupational therapist (OT) evaluations have been introduced into Emergency Department (ED) care to assist with fall risk evaluation and fall prevention care. An evaluation of current evidence was undertaken to inform the Geriatric ED Guidelines 2.0. Methods Systematic review of physical and/or occupational therapy evaluation for fall prevention in the ED. The intervention was evaluation by a rehabilitation therapist (PT, OT, or both) for fall prevention, fall assessment, or mitigation of fall risk factors. Studies that did not perform the evaluation during the ED or ED Observation Unit visit were excluded, such as referrals for home consultation. The published literature was searched using strategies created by a medical librarian and was implemented in Embase and PubMed in March 2025. Covidence was used for article collation and review. Risk of bias was assessed using the Cochrane Risk of Bias v2 and the Ottawa–Newcastle scale. Results The search resulted in 387 articles with 52 duplicates, for 335 unique citations. Ten articles on 6 datasets were included (4 abstracts and 6 published manuscripts). One article was at high risk of bias as very few intervention patients received therapist evaluation. The remaining 5 datasets had varied co‐interventions in addition to PT and/or OT evaluations. PT or OT evaluation in the ED was associated with reduced ED revisits at 1, 2, and 6 months. Evaluations in the ED were not associated with increased hospital admission rates or ED length of stay. A meta‐analysis was infeasible due to varied outcome timeframes. Conclusions PT and/or OT evaluations for fall prevention were associated with reduced subsequent ED revisits for older adults. However, the impact of co‐interventions and heterogeneity limits strong conclusions.