Citations

Autosomal dominant polycystic kidney disease (ADPKD), mainly driven by pathogenic variants in PKD1 and PKD2 , is the most common inherited cause of kidney failure. Details of ADPKD pathogenesis are incompletely resolved, but primary cilia are an integral component. There is also evidence for changes to the tubular basement membrane (TBM) in early disease. In this issue of the JCI , Mazloum and colleagues link cilia-dependent, PKD1-mediated regulation of the TBM to ADPKD pathogenesis. Using in vivo, ex vivo, tubule-on-chip, and cellular models of ADPKD, they connect cilia-dependent tubule dilation and TBM thinning to early-stage cystogenesis. Moreover, they identify a cilia-dependent TBM remodeling expression signature in affected tubules and suggest that PC1 loss compromises TBM stiffness. By integrating roles for cilia at the apical membrane and extracellular matrix at the basolateral membrane in cystogenesis, this work highlights the TBM as an additional area for investigation of therapeutic and biomarker discovery in ADPKD.

Summary Achalasia is a motility condition defined by failure of relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. Per-oral endoscopic myotomy (POEM) is a technique to reduce lower esophageal sphincter pressure. We performed a systematic review and meta-analysis to assess the association between POEM and the clinical outcomes. We performed a systematic review and a meta-analysis (CRD420251052240). Literature search was done on PubMed and Embase (up to 8 June 2025). Original studies involving achalasia patients who underwent esophageal POEM with impedance planimetry using 8-cm balloon at 30 or 40 mL filling volumes with 325 catheter only (not the 322-N catheter) were included. The outcomes of interest were the clinical response groups (responders’ Eckardt score [ES] < 3 and non-responders’ ES > 3), reflux esophagitis, cross-sectional area (CSA), distensibility index (DI), and diameter. Nineteen studies with 1215 patients were included. The responders (ES < 3) showed a statistically significantly greater increase in DI due to POEM (post-op minus pre-op) (mean difference [MD] = 1.92 mm2/mmHg [0.32, 3.53], P = 0.02) as well as a higher postoperative DI (MD = 1.87 mm2/mmHg [0.04, 3.70], P = 0.05) (40 mL). Reflux esophagitis group had statistically significantly higher CSA and diameter values (CSA MD = 15.68 mm2 [6.91, 24.24], P = 0.0005) (diameter MD = 0.96 mm [0.58, 1.33], P < 0.00001) but no statistically significant difference for DI as compared to the non-reflux esophagitis group (DI MD = 0.19 mm2/mmHg [−0.51, 0.89], P = 0.59). In achalasia patients undergoing esophageal POEM, a greater interval increase in the DI as well as a higher post-procedural DI absolute value predicts a favorable clinical response. Higher postoperative CSA and diameter were linked to reflux esophagitis.

Abstract Adipose‐derived cellular therapies (AD‐CTs) are increasingly used in orthopedics, yet the field lacks a standardized framework for classifying these heterogeneous products. Although prior efforts have standardized platelet‐rich plasma and bone marrow‐derived mesenchymal stromal cells, AD preparations remain inconsistently defined and poorly characterized. AD‐CTs encompass a range of products including enzymatically derived stromal vascular fraction, culture‐expanded adipose‐derived mesenchymal stromal cells (AD‐MSCs), and mechanically processed adipose tissue (AD‐MPT),each with distinct regulatory, cellular, and structural profiles. Unlike stromal vascular fraction and AD‐MSCs, which can be quantified using conventional assays, the intact extracellular matrix in AD‐MPTs complicates objective characterization. This paper introduces the Mechanical Processing (Harvesting) of Adipose Tissue classification system as a novel framework for standardizing the reporting of AD‐MPT harvesting and processing techniques that provides a structured approach to nomenclature and reporting. The system aims to enhance study comparability, facilitate research replication, and support the responsible advancement of adipose‐based therapies in musculoskeletal medicine.

Abstract Objective The goal of this study was to examine if differing platelet counts in platelet‐rich plasma (PRP) formulations affected overall pain and function outcomes when compared to hyaluronic acid or placebo control saline injections. Design/Methods We conducted a systematic review and meta‐analysis (International Prospective Register of Systematic Reviews CRD42022340057) evaluating randomized controlled trials comparing injections of PRP to hyaluronic acid (HA) or saline (NS) control in patients with mild or moderate knee osteoarthritis. All studies used a validated outcome measure that examined pain, function, or overall patient global assessment. Study PRP interventions were subclassified as investigating the total number of platelets delivered in a low dose (1–5 billion total deliverable platelets), moderate dose (5–10 billion total deliverable platelets), or high dose (greater than 10 billion total deliverable platelets) injected into the joint. Results A total of 32 trials met inclusion criteria. All three PRP groups had significant improvements in validated patient‐reported outcomes when compared to HA. Both the “low” and “high” platelet count groups resulted in a moderate effect size, respectively (standardized mean difference [SMD] = .47; 95% confidence interval [CI] .05–0.89, p < .01; SMD = .68; 95% CI .26–1.09, p < .01). Only the “moderate” (SMD = 1.48; 95% CI .71–2.58 p < .01) platelet count group resulted in large effect size on validated patient‐reported outcomes. When compared to NS, all three PRP groups resulted in significant large effect sizes when examining pain reduction. Conclusions When compared to HA, PRP with platelet counts between 1 and 10 billion total deliverable platelets may result in a larger decrease in pain symptoms when compared to platelet counts greater than 10 billion at 6 months. In addition, platelet counts between 5 and 10 billion total deliverable platelets may be associated with greater improvement in functional outcomes.

Listing and transplanting patients with acute liver failure (ALF) is challenging, requiring rapid assessment of the likelihood of recovery. The availability of a large number of ALF liver explants, along with their clinical data, afforded an opportunity to retrospectively evaluate liver transplantation (LT) decision-making. We hypothesized that, with the benefit of hindsight, a small number of patients might have recovered without LT. Three hundred liver explants from ALF patients of varying etiologies who had undergone LT over 22 years in the Acute Liver Failure Study Group registry were reviewed for histopathological features and degree of necrosis by a committee of 8 hepatopathologists. A second committee of 8 experienced transplant hepatologists independently reviewed clinical data on these same 300 patients and retrospectively scored the likelihood that each patient required transplantation. Only 3 (1%) of those reviewed by the Clinical Committee were considered to “Definitely” not require liver grafting, while an additional 10 (3.3%) were deemed to “Possibly” not require transplantation (Not Likely Group, N=13). There was no difference in the degree of necrosis in explants in these groups, when compared to the remaining Likely Group, N=287 (95.6%), except in acetaminophen (APAP)-associated ALF, where the degree of necrosis was more uniformly graded as severe, correlating with the need for transplantation. Virtually every patient undergoing LT for ALF retrospectively appeared to need their transplant, based on expert clinical consensus review. Overall, there was poor correlation between clinical severity and apparent degree of necrosis seen in the 300 liver explants, except perhaps for APAP subjects.

Background Secondary aortoenteric fistulas (SAEF) following endovascular aortic repair (EVAR) is an extremely rare event but life threatening. Our review offers comprehensive knowledge on pathophysiology, clinical presentation, diagnosis, and treatment options. Aim To summarize the current literature regarding pathophysiology, clinical, diagnostic and therapeutic approach of aortoenteric fistulas secondary to EVAR. Methods We performed a literature search in Pubmed/MEDLINE to identify the literature published about SAEF after EVAR. Cases were summarized in a table and prevalences. Other relevant literature was included in the results sections. Results A total of 35 reports (single cases and small series) with 45 patients were included. SAEF after EVAR can result from infection, inflammation, or mechanical factors. Clinical presentation is often non-specific, ranging from a gastrointestinal herald bleed to hemorrhagic shock, or malaise and general infection-related symptoms. Cross-sectional imaging plays a critical role in diagnosing SAEF. The treatment approach involves a multidisciplinary team approach and requires broad-spectrum intravenous antibiotics, endovascular intervention for urgent hemorrhage control, and open surgical intervention for definitive repair. Long-term antimicrobial therapy is essential to avoid reinfection. Conclusions SAEF following EVAR represents a complex, life-threatening condition with limited evidence-based management strategies. Given the growing prevalence of endovascular procedures, comprehensive knowledge of SAEF is crucial for all health care providers to improve early diagnosis and outcomes.

Abstract Objective: To better understand clinicians’ rationale for ordering testing for C. difficile infection (CDI) for patients receiving laxatives and the impact of the implementation of a clinical decision support (CDS) intervention. Design: A mixed-methods, case series was performed from March 2, 2017 to December 31, 2018. Setting: Yale New Haven Hospital, a 1,541 bed tertiary academic medical center. Participants: Hospitalized patients ≥ 18 years old, and clinicians who were alerted by the CDS. Intervention: CDS was triggered in real-time when a clinician sought to order testing for CDI for a patient who received one or more doses of laxatives within the preceding 24 hours. Results: A total of 3,376 CDS alerts were triggered during the 21-month study period from 2,567 unique clinician interactions. Clinicians bypassed the CDS alert 74.5% of the time, more frequent among residents (48.3% bypass vs. 39.9% accept) and advanced practice providers (APPs) (34.9% bypass vs. 30.6% accept) than attendings (11.3% bypass vs. 22.5% accept). Ordering clinicians noted increased stool frequency/output (48%), current antibiotic exposure (34%), and instructions by an attending physician to test (28%) were among the most common reasons for overriding the alert and proceeding with testing for CDI. Conclusions: Testing for CDI despite patient laxative use was associated with an increased clinician concern for CDI, patient risk for CDI, and attending physician instruction for testing. Attendings frequently accepted CDS guidance while residents and APPs often reinstated CDI test orders, suggesting a need for greater empowerment and discretion when ordering tests.

Background: Pathologic reflux is a common debilitating digestive condition and anti-reflux surgery is an effective treatment option. Depending on the specifics of the procedure, anti-reflux surgery leads to distinct changes in the endoscopic appearance of the esophagogastric junction (EGJ). This American Foregut Society (AFS) white paper develops nomenclature for describing the endoscopic characteristics of the EGJ after commonly performed laparoscopic antireflux operations. Methods: The AFS Anti-Reflux Barrier Collaborative analyzed the anatomic manipulation and corresponding endoscopic appearance of the EGJ after commonly performed anti-reflux surgery including: (1) 360° anterior/posterior (AP) fundoplication (Nissen); (2) posterior partial fundoplication (Toupet); (3) anterior partial fundoplication (Watson, Dor); (4) magnetic sphincter augmentation; and (5) concomitant hiatal hernia repair with transoral fundoplication (cTIF). Results: Characteristics common to the anti-reflux surgery procedures include restoration of intra-abdominal esophageal length and crural diaphragm repair such that the hiatal aperture is no longer visible in the retroflexed endoscopic view. With regard to the geometry of anti-reflux procedures, the Collaborative established that when evaluated endoscopically in retroflection, the surgically constructed valve should be described in reference to the angle of His and the extent of anatomic change described in terms of (1) the depth of the anterior and posterior grooves, (2) the apposition of the valve collar to the endoscope, (3) the length of the valve, and (4) the position of the squamocolumnar junction relative to the lip of the valve. Conclusions: Current anti-reflux operations share much in common but employ varying degrees of valvular reconstruction leading to distinct endoscopic characteristics. Developing a consistent nomenclature for describing the appearance of the post-surgical valve is essential to develop a better understanding of how variables such as the tightness of the hiatal repair, tightness of the valve collar, and length of the valve can impact the outcome of anti-reflux surgery and predict reflux recurrence.

Abstract Introduction: Tribal Nations across the Southwest have striking disparities in cancer incidence and mortality. Compounded by disproportionately low rates of cancer screening and limited access to healthcare, Native Americans are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States. At the University of New Mexico Comprehensive Cancer Center, the Participant Engagement Cancer Genomic Sequencing (PE-CGS) Center is developing culturally appropriate materials and strategies to enhance the engagement and recruitment of Native Americans into genomic research. This effort aims to determine participant knowledges, attitudes, cultural beliefs, and communication preferences regarding clinical genomics testing. Ultimately, targeting improvement of cancer outcomes in Southwestern Tribal communities. Cultural adaptations are crucial with regards to biospecimen collection, storage, and usage, due to historical mistrust of research among Native communities. (i.e., Havasupai Tribe v. the Arizona Board of Regents). A Tribal Advisory Committee, consisting of Tribal leaders, Native physicians, and patient advocates oversee all aspects of the research study. The goal is to identify appropriate optimized health literacy strategies for engaging Native peoples in cancer genomic research. Methods: The team conducted semi-structured discussions with participants to understand their perspectives on motivations to join, cultural safety components, and effectiveness of engagement strategies. With participant consent, the discussions were recorded and transcribed. Analysis included the transcripts and notes taken by the interviewer and followed Grounded Theory principles. All transcripts and notes followed line-by-line analysis by three of the authors (JS, JR and TG) who met regularly to identify and discuss emergent themes. Results: As of May 31, 2024, the PE-CGS study has enrolled 112 participants and completed 39 discussions. Participants emphasized altruistic motives tied to family and community, echoing traditional values, in their decision to participate in the study. This notion emerged during interactions with Native team members, where comfort stemmed from shared experiences (healthcare system, barriers), use of Native language, and adherence to Native social norms. Additional considerations included present autonomy throughout various stages of the study (sample use, data sharing, discussions). Return of genetic testing results improved understanding of treatment options, hereditary risk, and health literacy. Conclusion: Feedback highlights the importance of aligning cultural beliefs with Western medicine through a strengths-based approach. The findings will inform improvements in respectful engagement, communication, information exchange, and recruitment processes with Native American cancer patients and cancer survivors to genomic testing studies. Citation Format: Jessica Sanchez, Koby Blackwater, Joseph Rodman, Tamar Ginossar, Andrew Sussman, Shiraz Mishra, Cindy Blair, Mallery Quetawki, Debra MacKenzie, V. Shane Pankratz, Ursa Brown-Glaberman, Jeffery Trent, Cheryl Willman. Journey to understanding indigenous peoples engagement in cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A084.