tbuckley/cabot-search huggingface dataset:
Intra-Articular Platelet-Rich Plasma Injection After Anterior Cruciate Ligament Reconstruction
Authors: Zipeng Ye, Huiang Chen, Yi Qiao, Chenliang Wu, Eunshinae Cho, Xiulin Wu, Ziyun Li, Jinlong Wu, Simin Lu, Guoming Xie, Shikui Dong, Junjie Xu, Jinzhong Zhao
Journal: JAMA Network Open (2024)

Importance Platelet-rich plasma (PRP) has been considered a promising treatment for musculoskeletal disorders. The effects of PRP on clinical outcomes of anterior cruciate ligament reconstruction (ACLR) are controversial. Objective To compare subjective outcomes and graft maturity in patients undergoing ACLR with and without postoperative intra-articular PRP injection. Design, Setting, and Participants This surgeon- and investigator-masked randomized clinical trial included patients treated at a national medical center in China who were aged 16 to 45 years and scheduled to undergo ACLR. Participants were enrolled between March 21, 2021, and August 18, 2022, and followed up for 12 months, with the last participant completing follow-up on August 28, 2023. Interventions Participants were randomized 1:1 to the PRP group (n = 60), which received 3 doses of postoperative intra-articular PRP injection at monthly intervals, or to the control group (n = 60), which did not receive postoperative PRP injection. Both groups had the same follow-up schedule. Main Outcomes and Measures The primary outcome was the mean score for 4 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS 4 ) (range, 0-100, with higher scores indicating better knee function and fewer symptoms) at 12 months postoperatively. Secondary outcomes were patient-reported outcomes, graft maturity (on magnetic resonance imaging), and physical examinations at 3, 6, and 12 months. Results Among the 120 randomized participants (mean [SD] age, 29.0 [8.0] years; 84 males [70%]), 114 (95%) were available for the primary outcome analysis. The mean KOOS 4 scores at 12 months were 78.3 (SD, 12.0; 95% CI, 75.2-81.4) in the PRP group and 76.8 (SD, 11.9; 95% CI, 73.7-79.9) in the control group (adjusted mean between-group difference, 2.0; 95% CI, −2.3 to 6.3; P = .36). Secondary outcomes were not statistically significantly different between the 2 groups except for sports and recreation level and graft maturity at 6 months. Intervention-related adverse events included pain at the injection site and knee swelling after injection. Conclusions and Relevance In this randomized clinical trial among patients undergoing ACLR, the addition of postoperative intra-articular PRP injection did not result in superior improvement of knee symptoms and function at 12 months compared with no postoperative injection. Further studies are required to determine appropriate indications for PRP in musculoskeletal disorders. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2000040262
US County-Level Variation in Availability and Prevalence of Black Physicians in 1906
Authors: Benjamin W. Chrisinger
Journal: JAMA Network Open (2024)

Importance Black physicians are substantially underrepresented in the US health care workforce, with detrimental effects on the health and health care experiences of Black individuals. These contemporary gaps can be traced to the early days of the medical profession using the first edition of the American Medical Directory (AMD). Objective To identify state- and county-level patterns related to the training and availability of Black physicians relative to their White counterparts in the 1906 AMD. Design, Setting, and Participants For this cross-sectional study, data for 41 828 physician entries in 18 US states in or adjacent to the South as well as the District of Columbia were extracted from the 1906 AMD and aggregated to 1570 counties. Data analysis was performed between September 2023 and January 2024. Exposures County-level exposure variables included population density, racial composition, and illiteracy rate among US-born White residents as well as an index of terrain ruggedness and the number of lynchings in the previous decade. Median values of physicians’ distance from place of practice to place of medical training (by race of physician) were also used as an exposure variable. Main Outcomes and Measures There were 4 county-level outcomes: (1) presence of any Black physician, (2) proportion of Black physicians per Black population, (3) proportion of White physicians per White population, and (4) community representativeness (reported as the community representativeness ratio). The cross-sectional analysis used generalized additive mixed models with state-level random effects. Results Across 1570 counties, Black physicians comprised 746 (1.8%) of the 41 828 physicians in the dataset. Black physicians tended to train further from their place of practice than their White counterparts. The proportion of Black physicians per 1000 Black residents was 0.08 compared with 1.62 for White physicians; these proportions varied substantially by state. At the county level, the presence of any Black physician was associated with percentage Black population (odds ratio [OR], 28.94 [95% CI, 9.77 to 85.76]; P ≤ .001), population density (OR, 2.63 [95% CI, 2.03 to 3.40]; P ≤ .001), and distance to the nearest Black medical school (OR, 0.62 [95% CI, 0.42 to 0.92]; P = .02). Conclusions and Relevance A variety of structural disadvantages are illustrated in this cross-sectional study of county-level sociodemographic and geographic characteristics associated with the prevalence of Black physicians in the earliest days of the profession. To demonstrate its broader utility for health disparities research, the dataset has been made publicly available with a visualization platform.
Venous Thromboembolism Risk Assessment Models for Acutely Ill Medical Patients—Back to the Drawing Board?
Authors: Lara N. Roberts, Roopen Arya
Journal: JAMA Network Open (2024)

Emmanuel Häfliger, MD; Basil Kopp; Pauline Darbellay Farhoumand, MD; Damien Choffat, MD; Jean-Benoît Rossel, PhD; Jean-Luc Reny, MD, PhD; Drahomir Aujesky, MD, MSc; Marie Méan, MD; Christine Baumgartner, MD, MAS
Iron homeostasis, recycling and vulnerability in the stressed kidney: A neglected dimension of iron‐deficient heart failure
Authors: Milton Packer
Journal: European Journal of Heart Failure (2024)

Abstract The available evidence suggests that the kidney may contribute importantly to the development of an iron deficiency state in patients with heart failure and may be injured by therapeutic efforts to achieve iron repletion. The exceptional workload of the proximal renal tubule requires substantial quantities of iron for ATP synthesis, which it derives from Fe 3+ bound to transferrin in the bloodstream. Following ferrireduction, Fe 2+ is conveyed by divalent transporters (e.g. DMT1) out of the endosome of the proximal renal tubule, and highly reactive Fe 2+ can be directed to the mitochondria, sequestered safely in a ferritin nanocage or exported through the actions of hepcidin‐inhibitable ferroportin. The actions of ferroportin, together with transferrin endocytosis and DMT1‐mediated transport, play a key role in the recycling of iron from the tubular fluid into the bloodstream and preventing the loss of filtered iron in the urine. Activation of endogenous neurohormonal systems and proinflammatory signalling in heart failure decrease megalin‐mediated uptake and DMT1 expression, and increase hepcidin‐mediated suppression of ferroportin, promoting the loss of iron in the urine and contributing to the development of an iron deficiency state. Furthermore, the failure of ferroportin‐mediated efflux at the basolateral membrane heightens the susceptibility of the renal tubules to cytosolic excesses of Fe 2+ , causing lipid peroxidation and synchronized cell death (ferroptosis) through the iron‐dependent free radical theft of electrons from lipids in the cell membrane. Ferroptosis is a central mechanism to most disorders that can cause acute and chronic kidney disease. Short‐term bolus administration of intravenous iron can cause oxidative stress and is accompanied by markers of renal injury. Experimentally, long‐term maintenance of an iron‐replete state is accompanied by accelerated loss of nephrons, oxidative stress, inflammation and fibrosis. Intravenous iron therapy increases glomerular filtration rate rapidly in patients with heart failure (perhaps because of a haemodynamic effect) but not in patients with chronic kidney disease, and the effects of intravenous iron on the progression of renal dysfunction in the long‐term trials — AFFIRM‐AHF, IRONMAN and HEART‐FID — have not yet been reported. Given the potential role of dysregulated renal iron homeostasis in the pathogenesis of iron deficiency and the known vulnerability of the kidney to intravenous iron, the appropriate level of iron repletion with respect to the risk of acute and chronic kidney injury in patients with heart failure requires further study.
Critical re‐evaluation of the identification of iron deficiency states and effective iron repletion strategies in patients with chronic heart failure
Authors: Milton Packer, Stefan D. Anker, Javed Butler, John G.F. Cleland, Paul R. Kalra, Robert J. Mentz, Piotr Ponikowski, Khawaja M. Talha
Journal: European Journal of Heart Failure (2024)

Abstract According to current guidelines, iron deficiency is defined by a serum ferritin level &lt;100 ng/ml or a transferrin saturation (TSAT) &lt;20% if the serum ferritin level is 100–299 μg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis‐stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT—but not serum ferritin level—appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT &lt;20% (risk ratio 0.67 [0.49–0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74–1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level &lt;100 μg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20–300 μg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level &lt;100 μg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of &gt;300 μg/L. Importantly, analyses of benefit based on trial eligibility‐driven guidelines substantially underestimate the magnitude of heart‐failure‐event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism‐based and trial‐tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT &lt;20% (as long as the serum ferritin level is &lt;400 μg/L), and furthermore, the use of a serum ferritin level &lt;100 μg/L alone as a diagnostic criterion should be discarded.
GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery
Authors: Casper W.F. van Eijck, Francisco X. Real, Núria Malats, Disha Vadgama, Thierry P.P. van den Bosch, Michail Doukas, Casper H.J. van Eijck, Dana A.M. Mustafa
Journal: Cell Reports Medicine (2024)

This study underscores GATA6's role in distinguishing classical and basal-like pancreatic ductal adenocarcinoma (PDAC) phenotypes. Retrospective studies associate GATA6 immunohistochemistry (IHC) expression with survival outcomes, warranting prospective validation. In a prospective treatment-naive cohort of patients with resected PDAC, GATA6 IHC proves a prognostic discriminator, associating high GATA6 expression with extended survival and the classical PDAC phenotype. However, GATA6's prognostic significance is numerically lower after gemcitabine-based neoadjuvant chemoradiotherapy compared to its significance in patients treated with upfront surgery. Furthermore, GATA6 is implicated in immunomodulation, although a comprehensive investigation of its immunological role is lacking. Treatment-naive PDAC tumors with varying GATA6 expression yield distinct immunological landscapes. Tumors highly expressing GATA6 show reduced infiltration of immunosuppressive regulatory T cells and M2 macrophages but increased infiltration of immune-stimulating, antigen-presenting, and activated T cells. Our findings caution against solely relying on GATA6 for molecular subtyping in clinical trials and open avenues for exploring immune-based combination therapies.
Meteorin‐like protein/METRNL/Interleukin‐41 ameliorates atopic dermatitis‐like inflammation
Authors: Danqi Huang, Xiuting Liu, Xun Gao, Chun Kit Choi, Giovanni Giglio, Luay Farah, Ting‐Fan Leung, Katie Ching‐Yau Wong, Lea Ling‐Yu Kan, Jeffrey Wing‐Heung Chong, Qing‐Jun Meng, Jinyue Liao, Phyllis Fung‐Yi Cheung, Chun‐Kwok Wong
Journal: Allergy (2024)

Meteorin-like protein (METRNL)/Interleukin-41 (IL-41) is a novel immune-secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD). METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903-induced AD-like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single-cell RNA-seq and RNA-seq. METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced β-Catenin activation, limited the expression of Th2-related molecules that attract the accumulation of Arginase-1 (Arg1)hi macrophages, dendritic cells, and activated mast cells. METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule β-Catenin.
Implementation of Universal Hepatitis C Virus Screening in a Tertiary Cancer Center
Authors: Harrys A. Torres, Khalis Mustafayev, Ruston P. Juneau, Jessica P. Hwang, Lan Sun Wang, Georgios Angelidakis, Ernest Hawk, Bruno P. Granwehr, Eduardo Yepez Guevara, Anita K. Ying
Journal: Journal of the National Comprehensive Cancer Network (2024)

The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center.
Exploring the universe of HIV post-exposure prophylaxis in trans women: A qualitative analysis of access, use and adherence
Authors: Kamila Cardoso dos Santos, Larissa Silva Magalhães, Karlla Antonieta Amorim Caetano, Jeanne-Marie R. Stacciarini, Leonora Pacheco Rezende, Vanessa da Silva Carvalho Vila, Christopher Wagstaff, Sandra Cristina Pillon, Sheila Araujo Teles
Journal: International Journal of Transgender Health (2024)

Introduction Post-exposure prophylaxis (PEP) for HIV, a form of emergency prevention, has been available for more than two decades. However, information about its use among trans women, a group disproportionately affected by HIV, is limited.
Ecological insights into hematopoiesis regulation: unraveling the influence of gut microbiota
Authors: Kaiwen Zheng, Zhifeng Wei, Wei Li
Journal: Gut Microbes (2024)

The gut microbiota constitutes a vast ecological system within the human body, forming a mutually interdependent entity with the host. In recent years, advancements in molecular biology technologies have provided a clearer understanding of the role of the gut microbiota. They not only influence the local immune status and metabolic functions of the host's intestinal tract but also impact the functional transformation of hematopoietic stem cells (HSCs) through the gut-blood axis. In this review, we will discuss the role of the gut microbiota in influencing hematopoiesis. We analyze the interactions between HSCs and other cellular components, with a particular emphasis on the direct functional regulation of HSCs by the gut microbiota and their indirect influence through cellular components in the bone marrow microenvironment. Additionally, we propose potential control targets for signaling pathways triggered by the gut microbiota to regulate hematopoietic function, filling crucial knowledge gaps in the development of this research field.
<i>Prevotella copri</i> promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway
Authors: Qing-Yun Hao, Jing Yan, Jin-Tao Wei, Yu-Hong Zeng, Li-Yun Feng, Dong-Dong Que, Shi-Chao Li, Jing-Bin Guo, Ying Fan, Yun-Fa Ding, Xiu-Li Zhang, Ping-Zhen Yang, Jing-Wei Gao, Ze-Hua Li
Journal: Gut Microbes (2024)

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.
The experiences of transgender and gender diverse children and youth using telehealth: a meta-ethnography
Authors: Josh Vriends, Holly Symonds-Brown
Journal: International Journal of Transgender Health (2024)

Background Transgender and gender diverse (TGD) children and youth face significant disparities when accessing healthcare. Telehealth has become a promising strategy for improving healthcare access. The experiences of TGD children and youth using telehealth to access healthcare are poorly understood.
Clinical and biological characterization of involvement of nasal‐associated lymphoid tissues in chronic lymphocytic leukemia
Authors: Thimali Ranaweera Arachchige, Catherine Mendiburu, Antoine Martin, Carole Fleury, Elisabetta Dondi, Rémi Letestu, Virginie Eclache, Fanny Baran‐Marszak, Florence Cymbalista, Gregory Lazarian
Journal: American Journal of Hematology (2024)
Clinical Trials for Kidney Disease in the Era of Personalized Medicine
Authors: Hiddo J.L. Heerspink, Matthias Kretzler
Journal: Journal of the American Society of Nephrology (2024)

1Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 2Department of Medicine-Nephrology and Computational Medicine and Bioinformatics University of Michigan, Ann Arbor, MI, USA aCorresponding author Hiddo J.L. Heerspink Department of Clinical Pharmacy and Pharmacology University of Groningen Hanzeplein 1 PO Box 30 001 Groningen, The Netherlands Tel: +31 50 361 4071 E-mail: [email protected]
Enhancing oncogenic signaling to kill cancer cells
Authors: Maxim Noeparast, Oleg Timofeev, Martin Pichler
Journal: Trends in Pharmacological Sciences (2024)

Cancer-targeted therapies that inhibit oncogenic signaling often lead to resistance and recurrence. In a recent study, Dias et al. propose activating oncogenic pathways and inducing replication stress, resulting in cell death and tumor-suppressive mechanisms in colorectal cancer (CRC). This approach could spark a new wave of target discovery, and drug development and repurposing against cancer.