Citations

Background: There is growing evidence that social determinants of health (SDOH) are associated with disparities in access to care and hand and upper extremity health. Quality measures represent an opportunity to evaluate disparities in access and outcomes that can inform improvement interventions. We performed a systematic review of evidence regarding health disparities within hand surgery and aimed to develop suitable quality measures that are clinically important, feasible, usable, and scientifically acceptable. Methods: We performed a systematic review including common hand surgery terms to identify health disparities in hand surgery related to SDOH. Candidate quality measures were constructed based upon evidence from the systematic review. A consortium of 11 US-based hand and upper extremity surgeons completed a modified RAND/UCLA Delphi Appropriateness process to evaluate the importance, feasibility, usability, and scientific acceptability of the candidate quality measures. Panelists rated each measure on a scale of 1 ( definitely not important/feasible/usable/scientifically acceptable ) to 9 ( definitely important/feasible/usable/scientifically acceptable ) in 2 voting rounds separated by a face-to-face discussion. Agreement among panelists and validity were assessed using predetermined criteria. Results: Fourteen candidate quality measures addressing health disparities were identified based on evidence from the systematic review, including time to surgery and emergency department use after hand surgery based on insurance type, clinical outcomes based on social deprivation, among others. All 14 measures were accepted. Conclusions: Fourteen candidate quality measures were identified and accepted based upon consensus to address health disparities in hand surgery, although future investigation will be needed to evaluate their effectiveness.

Vanishing bile duct syndrome is a rare complication of classical Hodgkin’s lymphoma (cHL) which may present with significant cholestasis and hepatic dysfunction. Management is primarily focused on chemotherapy and symptomatic management of cholestatic liver failure. We describe a case of a man in his 60s with relapsed cHL with significant cholestatic liver injury who was treated with brentuximab vedotin complicated by renal failure. The complex decision-making surrounding chemotherapeutic choice with the presence of multiorgan dysfunction is discussed with a review of literature describing regimens in similar clinical circumstances.

Abstract Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort ( n = 5136) and transcriptomic data from a prospective cohort ( n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “ TP53 ‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML‐like, bi TET2 , SF3B1 , and TP53 ‐complex subgroups. Further integration of multi‐omics data may refine MDS classification, improving clinical decision‐making and guiding the development of targeted therapies.

Multiple sclerosis is an immune-driven neurological disease that affects myelinated axons in the central nervous system. However, the trigger of the (dysregulated) immune reactions is not known. According to Wilkin’s primary lesion theory, myelin-reactive T cells present in the immune repertoire hyper-react to myelin antigens that are released from idiopathic lesions within the central nervous system. However, neither the cause of the primary lesion nor the cause of the immune hyper-reactivity is known. We investigated whether these unknown activation signals may be relayed by common herpesviruses. In this concept paper, we propose the novel paradigm that the trigger of autoimmunity in MS comprises a conspiracy of three common herpesviruses: human herpesvirus-6A as a potential trigger of primary lesions due to its proven capacity to cause oligodendrogliopathy, cytomegalovirus as a trigger for the formation of effector memory cytotoxic T cells with proven capacity to induce multiple sclerosis pathology in a non-human primate MS model and Epstein-Barr Virus due to its capacity to render B cells capable to effectively present a critical myelin antigen to these effector memory cytotoxic T cells.

Background: Hepatic stellate cells (HSCs) play a pivotal role in driving fibrosis during chronic liver injury. HSCs produce vast amounts of fibrotic proteins, causing endoplasmic reticulum (ER) stress and initiating the unfolded protein response (UPR). While the UPR is important for fibrogenesis, how signaling through UPR transducer Protein Kinase R-like ER Kinase (PERK) and its effectors impact HSC activation and fibrogenesis is unclear. Here, we sought to uncover the role of PERK and its effector GADD45A in liver fibrosis. Methods: PERK–GADD45A signaling was assessed in primary and immortalized HSCs treated with TGFβ, and mouse models of fibrosis. Genetic and pharmacological disruption of PERK or GADD45A was used to assess the role of PERK or GADD45A in HSC activation, proliferation, and fibrogenesis. HSC-specific Gadd45a -null mice were utilized to investigate the role of GADD45A on CCl 4 -induced fibrosis. Results: We found that TGFβ-induction of collagen I drives activation of PERK signaling in HSCs. Furthermore, loss or inhibition of PERK limits long-term HSC activation as illustrated by reduced levels of collagen I and fibronectin, impaired collagen I deposition, and reduced cell proliferation in vitro. Next, we show that PERK signaling induces expression of GADD45A during HSC activation, and loss of GADD45A disrupts HSC activation and expression of proliferation and cell-cycle-associated genes in immortalized and primary HSCs. Finally, HSC-specific GADD4Aa loss limits CCl 4 -driven fibrogenesis in vivo. Conclusion: PERK signaling is critical for HSC activation, and loss of the PERK downstream effector GADD45A limits fibrosis progression. Disruption of HSC activation and proliferation, coupled with dysregulation of cell-cycle-associated genes upon PERK or GADD45A loss, suggests that PERK–GADD45A signaling impacts multiple facets of HSC pathophysiology.

Background: Despite recent advances in cleft care, Vietnam continues to have extensive involvement from international nongovernmental organizations (NGOs), creating a fragmented system with limited coordination. This project seeks to establish a baseline understanding of Vietnam’s cleft care landscape, including major international NGOs and their collaborations with local partners, costs and insurance coverage, and patterns applicable to other low- and middle-income countries with NGO-supported cleft care. Methods: We conducted a mixed-methods study using literature review and semi-structured interviews with surgeons, hospital administrators, and NGO representatives (n = 7). Sources included PubMed, targeted Google searches, and government regulations on NGO involvement, cleft care costs, and insurance policies. Results: Vietnam partners with 17 international NGOs that operate through 3 distinct but complementary models: vertical, horizontal, and diagonal models. These collaborations offer financial support, infrastructure, technology investment, and research development, leading to higher surgical volume, more timely access to care, and implementation of standardized multidisciplinary cleft services in Vietnam. National insurance provides broad coverage but requires a complex referral process with limited benefits for secondary cleft services. Limited awareness of insurance benefits and mistrust of local care further discourage the use of national health insurance. Conclusions: Improving access to comprehensive cleft services in Vietnam requires streamlining insurance referral pathways and decentralizing advanced cleft services to regional centers to ensure continuity of care. Aligning NGO activities with national policies is essential to building a coordinated and sustainable cleft care system in Vietnam and in other low- and middle-income countries with strong insurance frameworks and significant NGO involvement.

Background Gastro-oesophageal reflux disease (GORD) occurs in most (∼75%) patients with systemic sclerosis (SSc) and significantly impacts quality of life. Current recommendations lack depth and therefore our aim was to produce practical, consensus-based recommendations for refractory SSc-related GORD. Methods An international, multidisciplinary steering board (SB) was assembled (n=19) consisting of clinicians (rheumatologists, gastroenterologists, gastrointestinal surgeons), an expert methodologist and patient representation. After reviewing the latest definitions of GORD and refractory GORD in the published literature, the SB collectively devised a practical definition of SSc refractory-GORD. Initial recommendations were drafted/agreed on by the SB based on review of the existing guidelines, published literature and expert opinion. Two online voting rounds were conducted to determine whether items should be accepted, with >75% and >60% SB agreement required for first and second rounds, respectively. Results There was a good response/completion rate for the initial (74%) and final (84%) voting rounds. The SB agreed on all 36 draft recommendations. The majority (n=34) were approved in the first round. Recommendations were organised according to the following categories: general approach to management (n=5), assessment (n=6), non-pharmacological (n=2) and pharmacological (n=10) management, endoscopic and surgical treatment (n=3), and special circumstances including refractory GORD and SSc-interstitial lung disease (n=3), myositis and SSc connective tissue disease-overlap (n=3) and perilung transplant (n=4). Conclusion The group of experts has drafted extended and practical recommendations for the management of SSc refractory-GORD. The necessity of a structured approach and a patient assessment is highlighted in order to provide a multidisciplinary approach to the tailored choice of the treatment. Our work also has also identified significant unmet needs and has provided a research agenda to advance the field.

Objective: Percutaneous needle tenotomy (PNT) and ultrasonic debridement (UD) are minimally invasive interventions for the management of chronic tendinopathy. Despite their increasing use, no standardized, evidence-based rehabilitation guidelines currently exist to direct clinicians in post-procedural management. This systematic review aimed to characterize and synthesize reported rehabilitation protocols following PNT and UD for patellar, proximal hamstring, and gluteal tendinopathies. Design: Systematic Review Results: Twenty-seven studies met inclusion criteria, with patellar tendon procedures (n=13) being the most common, followed by gluteal (n=6), proximal hamstring (n=3), and multi-tendon protocols (n=5). Of the included studies, 21 (78%) utilized percutaneous needle tenotomy (PNT) and six (22%) used ultrasound debridement or Tenex. Exercise restrictions were mandated in 19 studies (70%), while 12 (44%) provided a detailed, structured rehabilitation program, frequently emphasizing eccentric loading for patellar and hamstring tendons. Weight-bearing limitations were uncommon, appearing in only three studies (11%). Fifteen studies (56%) combined the procedure with platelet-rich plasma (PRP). Pharmacological protocols also showed high variance, with NSAID restrictions ranging from 1 to 28 days and corticosteroid avoidance lasting between 10 days and one year. Overall, substantial variability remains regarding recommended activity progression, exercise initiation, and mechanical loading strategies across current research. Conclusion: PNT and UD appear effective for managing refractory tendinopathy, yet post-procedure rehabilitation guidelines remain inconsistent and supported by limited high-quality evidence. Future research should aim to identify key variables that guide individualized rehabilitation progressions, optimizing recovery timelines, and facilitating safe and efficient return to activity following PNT and UD procedures.