tbuckley/cabot-search huggingface dataset:
Outcomes by Race and Ethnicity Following a Medicare Bundled Payment Program for Joint Replacement
Authors: Narae Kim, Mireille Jacobson
Journal: JAMA Network Open (2024)

Importance The Comprehensive Care for Joint Replacement (CJR) model, a traditional Medicare bundled payment program for lower-extremity joint replacement, is associated with care for patients outside traditional Medicare. Whether CJR model outcomes have differed by patient race or ethnicity outside of traditional Medicare is unclear. Objective To evaluate outcomes associated with the CJR model among Hispanic patients not enrolled in traditional Medicare. Design, Setting, and Participants This cohort study used hospitalization data from California’s Patient Discharge Dataset for all patients who underwent lower-extremity joint replacement in California between January 1, 2014, and December 31, 2017. In California, 3 metropolitan statistical areas (MSAs) were randomly selected to participate in CJR in April 2016. Hospitals not participating in other Medicare Alternative Payment Models were included in the treated group if they were in these 3 MSAs and in the control group if they were in the remaining 23 MSAs. The data analysis was performed between October 1 and December 31, 2023. Exposure Comprehensive Care for Joint Replacement program implementation. Main Outcomes and Measures The main outcomes were hospital length of stay and home discharge rates by race and ethnicity. Home discharge status included self-care, the use of home health services, and hospice care at home. Event study, difference-in-differences, and triple differences models were used to estimate differential changes in health care service use by race and ethnicity for patients in the treated MSAs compared with the control MSAs before vs after CJR implementation. Results Of 309 834 hospitalizations (patient mean [SD] age, 68.3 [11.3] years; 60.6% women; 14.8% Hispanic; 72.4% non-Hispanic White), 48.0% were in treated MSAs and 52.0% in control MSAs. The CJR program was associated with an increase in home discharge rates for patients without traditional Medicare coverage; however, the increase differed by patient race and ethnicity. The increase was 0.05 (95% CI, 0.02-0.08) percentage points higher for Hispanic patients with Medicare Advantage and 0.03 (95% CI, 0.01-0.04) percentage points higher for Hispanic patients without Medicare compared with their non-Hispanic White counterparts. Conclusions and Relevance This cohort study shows that CJR program outcomes differed by race and ethnicity for patients covered outside traditional Medicare, with home discharge rates increasing more for Hispanic compared with non-Hispanic White patients. These findings suggest the importance of considering differential outcomes of Medicare payment policies for racial and ethnic minority patient populations beyond the initially targeted groups.
Excess Body Weight and the Risk of Second Primary Cancers Among Cancer Survivors
Authors: Clara Bodelon, Hyuna Sung, Ellen L. Mitchell, Emily L. Deubler, Christina C. Newton, Ahmedin Jemal, Lauren R. Teras, Alpa V. Patel
Journal: JAMA Network Open (2024)

Importance Little is known about the causes of second primary cancers among individuals with a history of cancer. Descriptive studies have suggested that lifestyle factors, including excess body weight, may be important. Objective To investigate whether excess body weight is associated with the risk of a second primary malignant neoplasm among cancer survivors. Design, Setting, and Participants This cohort study of adults in 21 states in the US used data from the Cancer Prevention Study II Nutrition cohort, a large prospective study that invited participants to respond to a survey in 1992 and biennial surveys starting in 1997, and who were followed-up through 2017. Eligible participants included those who received a diagnosis of a first primary nonmetastatic invasive cancer between 1992 and 2015. Data analysis occurred from September 2023 to March 2024. Exposure Body mass index (BMI), computed from self-reported height and weight at the time of the first primary cancer diagnosis (mean [SD] years to diagnosis, 1.7 [1.5] years). Main Outcome and Measures Main outcomes included a second primary cancer or an obesity-related second cancer. Cancer diagnoses were reported on biennial surveys and verified through medical record abstraction or linkage with state cancer registries. Results This cohort included 26 894 participants who received a diagnosis of a first nonmetastatic primary cancer (mean [SD] age at first cancer diagnosis, 72.2 [6.5] years; 15 920 male [59.2%]). At the time of first diagnosis, 11 497 participants (42.8%) had overweight and 4684 (17.2%) had obesity. During a median (IQR) follow-up time of 7.9 (3.4-13.6) years, 3749 (13.9%) participants received a diagnosis of a second primary cancer, of which 1243 (33.2%) were obesity-related second primary cancers. Compared with cancer survivors whose BMI was in the normal range (18.5 to &amp;amp;lt;25), there was 15% increased risk of any second primary cancer for those who had overweight (25 to &amp;amp;lt;30; adjusted hazard ratio [aHR], 1.15; 95% CI, 1.07-1.25) and a 34% increased risk for those who had obesity (BMI ≥30; aHR, 1.34; 95% CI, 1.21-1.48), with greater risk for obesity-related second primary cancers, including a 40% increased risk for those with overweight (aHR, 1.40; 95% CI, 1.22,-1.61) and a 78% increased risk for those with obesity (aHR, 1.78; 95% CI, 1.51-2.11). Conclusions and Relevance In this cohort study of older survivors of nonmetastatic cancer, those who had overweight or obesity at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially an obesity-related second cancer. Given the high prevalence of overweight and obesity among cancer survivors, it is important to promote survivorship care guidelines recommending weight management and increase awareness of second cancers among physicians and cancer survivors.
Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy
Authors: Marion Delcroix, Joanna Pepke-Zaba, Andrea M. D’Armini, Elie Fadel, Stefan Guth, Stephen P. Hoole, David P. Jenkins, David G. Kiely, Nick H. Kim, Michael M. Madani, Hiromi Matsubara, Kazuhiko Nakayama, Aiko Ogawa, Jaquelina S. Ota-Arakaki, Rozenn Quarck, Roela Sadushi-Kolici, Gérald Simonneau, Christoph B. Wiedenroth, Bedrettin Yildizeli, Eckhard Mayer, Irene M. Lang
Journal: Circulation (2024)

BACKGROUND: The European Chronic Thromboembolic Pulmonary Hypertension (CTEPH) registry, conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. METHODS: Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. RESULTS: Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Of patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes.s.cm −5 . During the observation period (&gt;3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention ( P &lt;0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non–vitamin K oral anticoagulants ( P =0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. CONCLUSIONS: This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02656238.
County-level jail and state-level prison incarceration and cancer mortality in the United States
Authors: Jingxuan Zhao, Sandhya Kajeepeta, Christopher R Manz, Xuesong Han, Leticia M Nogueira, Zhiyuan Zheng, Qinjin Fan, Kewei Sylvia Shi, Fumiko Chino, K Robin Yabroff
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract This study examined the association of county-level jail and state-level prison incarceration rates and cancer mortality rates in the United States. Incarceration rates (1995-2018) were sourced from national data and categorized into quartiles. County- and state-level mortality rates (2000-2019) with invasive cancer as the underlying cause of death were obtained from the National Vital Statistics System. Compared with the first quartile (lowest incarceration rate), the second, third, and fourth quartiles (highest incarceration rate) of county-level jail incarceration rate were associated with 1.3%, 2.3%, and 3.9% higher county-level cancer mortality rates, respectively, in adjusted analyses. Compared with the first quartile, the second, third, and fourth quartiles of state-level prison incarceration rate were associated with 1.7%, 2.5%, and 3.9% higher state-level cancer mortality rates, respectively. Associations were more pronounced for liver and lung cancers. Addressing adverse effects of mass incarceration may potentially improve cancer outcomes in affected communities.
Unraveling The Genetics of Shared Clinical and Serological Manifestations in Systemic Inflammatory Autoimmune Diseases
Authors: Matteo Bianchi, Sergey V. Kozyrev, Antonella Notarnicola, Johanna K. Sandling, Mats Pettersson, Dag Leonard, Christopher Sjöwall, Iva Gunnarsson, Solbritt Rantapää‐Dahlqvist, Anders A. Bengtsson, Andreas Jönsen, Elisabet Svenungsson, Helena Enocsson, Marika Kvarnström, Helena Forsblad‐d'Elia, Sara Magnusson Bucher, Katrine B. Norheim, Eva Baecklund, Roland Jonsson, Daniel Hammenfors, Per Eriksson, Thomas Mandl, Roald Omdal, Leonid Padyukov, Helena Andersson, Øyvind Molberg, Louise Pyndt Diederichsen, Ann‐Christine Syvänen, Marie Wahren‐Herlenius, Gunnel Nordmark, Ingrid E. Lundberg, Lars Rönnblom, Kerstin Lindblad‐Toh
Journal: Arthritis & Rheumatology (2024)

OBJECTIVES Systemic inflammatory autoimmune diseases (SIADs) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and idiopathic inflammatory myopathies (myositis) are complex conditions characterized by shared circulating autoantibodies and clinical manifestations, including skin rashes, among others. This study aimed at elucidating the genetics underlying these common features. METHODS We performed targeted DNA sequencing of coding and regulatory regions from ~1,900 immune‐related genes in a large SIAD cohort of 2,292 well‐characterized Scandinavian patients with SLE, pSS and myositis, as well as 1,252 controls. A gene‐based functionally‐weighted genetic score for aggregate testing of all genetic variants, including rare variants, was complemented by in‐silico functional analyses and in‐vitro reporter experiments. RESULTS Case‐control association analysis detected known and potentially novel genetic loci in agreement with previous genetic and transcriptomics findings linked to the SIAD autoimmune background. Intriguingly, case‐case comparisons between patient subgroups with and without specific autoantibodies revealed that the subgroups defined by ANA and anti‐dsDNA antibodies have unique genetic profiles reflecting their heterogeneity. When focusing on clinical features, we overall showed that DUSP1 protective genetic variants lead to increased gene expression and potentially to anti‐inflammatory effects on the SIAD‐associated skin phenotype. This is consistent with recent genetic findings on eczema and with the previously reported downregulation of the MAPK signaling‐related gene DUSP1 in other skin disorders. CONCLUSION Together, this suggests common molecular mechanisms potentially underlying overlapping clinical manifestations shared among different disorders and informs clinical heterogeneity, which could be translated to improve disease diagnostic and treatment, also in more generalized disease frameworks.
Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease
Authors: Abdoulaye Sissoko, Astan Cissé, Clémence Duverdier, Mickaël Marin, Lucie Dumas, Sandra Manceau, Blandine Maître, Anita Eckly, Aurélie Fricot‐Monsinjon, Camille Roussel, Papa Alioune Ndour, Michael Dussiot, Safi Dokmak, Béatrice Aussilhou, Jeanne Dembinski, Alain Sauvanet, François Paye, Mickaël Lesurtel, Jérôme Cros, Dominique Wendum, Magali Tichit, David Hardy, Carmen Capito, Slimane Allali, Pierre Buffet
Journal: American Journal of Hematology (2024)

In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long-term risk of asplenia-related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC-related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with Hb
Quantitative tissue analysis reveals AK2, COL1A1, &amp; PLG protein signatures: Targeted therapeutics for meningioma
Authors: Swati Sharma, Shamjetsabam Nandibala Devi, Kirti Chauhan, M.H. Yashavarddhan, Poonam Gautam, Prem Prakash, Priyanka Choudhary, Satnam Singh Chhabra, Rajesh Acharya, Samir Kumar Kalra, Anshul Gupta, Sunila Jain, Nirmal Kumar Ganguly, Rashmi Rana
Journal: International Journal of Surgery (2024)
Whole genomes inform genetic rescue strategy for montane red foxes in North America
Authors: Cate B Quinn, Sophie Preckler-Quisquater, Michael R Buchalski, Benjamin N Sacks
Journal: Molecular Biology and Evolution (2024)

Abstract A few iconic examples have proven the value of facilitated gene flow for counteracting inbreeding depression and staving off extinction, yet the practice is often not implemented for fear of causing outbreeding depression. Using genomic sequencing, climatic niche modeling, and demographic reconstruction, we sought to assess the risks and benefits of using translocations as a tool for recovery of endangered montane red fox (Vulpes vulpes) populations in the western United States. We demonstrated elevated inbreeding and homozygosity of deleterious alleles across all populations, but especially those isolated in the Cascade and Sierra Nevada ranges. Consequently, translocations would be expected to increase population growth by masking deleterious recessive alleles. Demographic reconstructions further indicated shallow divergences of less than a few thousand years among montane populations, suggesting low risk of outbreeding depression. These genomic-guided findings set the stage for future management, the documentation of which will provide a roadmap for recovery of other data-deficient taxa.
Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program
Authors: Steven G. Johnson, Sajjad Abedian, Til Stürmer, Jared D. Huling, Colby Lewis V, John B. Buse, Shari B. Brosnahan, Praveen C. Mudumbi, Kristine M. Erlandson, Grace A. McComsey, Jonathan Arnold, Talia D. Wiggen, Rachel Wong, Shawn Murphy, Clifford Rosen, Rainu Kaushal, Mark G. Weiner, Carolyn Bramante
Journal: Diabetes Care (2024)

Studies show metformin use before and during SARS-CoV-2 infection reduces severe COVID-19 and postacute sequelae of SARS-CoV-2 (PASC) in adults. Our objective was to describe the incidence of PASC and possible associations with prevalent metformin use in adults with type 2 diabetes mellitus (T2DM).
Comparison of prognostic scores according to <scp>WHO</scp> classification in 170 patients with advanced mastocytosis and C‐finding treated with midostaurin
Authors: Maël Heiblig, Clément Gourguechon, Philippe Guilpain, Cristina Bulai‐Livideanu, Stéphane Barete, Yannick Chantran, Julie Agopian, Fabienne Brenet, Patrice Dubreuil, Jérémie Lespinasse, Richard Lemal, Olivier Tournilhac, Louis Terriou, David Launay, Laurence Bouillet, Catharina Chatain, Ghandi Damaj, Thomas Ballul, Celine Greco, Laura Polivka, Laurent Frenzel, Cécile Meni, Hassiba Bouktit, Dina Benabou, Caroline Gaudy‐Marqueste, Marie Gousseff, Edwige Le Mouel, Antoine Neel, Dana Ranta, Roland Jaussaud, Thierry Jo Molina, Julie Bruneau, Patrick Villarese, Ludovic Lhermitte, Leila Maouche‐Chrétien, Marie Temple, Olivier Kosmider, Rose‐Marie Javier, Fabien Pelletier, Florence Castelain, Frederique Retornaz, Quentin Cabrera, Patricia Zunic, Marie Pierre Gourin, Ewa Wierzbicka–Hainaut, Jean François Viallard, Christian Lavigne, Cyrille Hoarau, Isabelle Durieu, Sophie Dimicoli‐Salazar, Jose Miguel Torregrosa‐Diaz, Mathieu Wemeau, Angèle Soria, Michel Arock, Christine Bodemer, Olivier Lortholary, Olivier Hermine, Julien Rossignol
Journal: American Journal of Hematology (2024)

Abstract Advanced systemic mastocytosis (AdvSM) encompasses heterogeneous mastocytosis subtypes and is associated with poor outcomes. Although midostaurin was the first tyrosine kinase inhibitor to be approved for AdvSM patients, long‐lasting responses are limited. The mutation‐Adjusted Risk Score (MARS), the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) have been established to characterize the outcomes of patients with overall AdvSM. However, given the outcome's dependency on the AdvSM subtype, prognostic characterization within each subtype is critical. We aimed to study the predictive ability using Harrell's concordance index of prognostic scores according to the AdvSM subtype. We conducted a nationwide retrospective study using the French mastocytosis reference center's registry and included all midostaurin‐treated patients with C finding. Overall, 170 patients were identified: 46 aggressive SM (ASM), 11 mast cell leukemia (MCL), and 113 SM with associated hematological neoplasm (SM‐AHN). All risk scores improved their discriminative value for overall survival (OS) when combined with the AdvSM subtype. The best predictive value was for adjusted MARS (C‐index = 0.689), followed by GPSM (C‐index = 0.677) and IPSM (C‐index = 0.618). In a multivariable analysis, MARS stratification and the AdvSM subtype were both prognostic for OS. Accordingly, five subgroups of patients with AdvSM and a different median OS were identified: 9.9 months for MCL, 24 months for intermediate/high‐risk SM‐AHN, 33 months for intermediate/high‐risk ASM, 58 months for low‐risk SM‐AHN and was not reached for low‐risk ASM ( p &lt; 0.001). The AdvSM subtype and the MARS are the most predictive of OS and should prompt specific management.
Prebiotic inulin controls Th17 cells mediated central nervous system autoimmunity through modulating the gut microbiota and short chain fatty acids
Authors: Ning Li, Xinyan Han, Ming Ruan, Fei Huang, Liu Yang, Tianhao Xu, Huijun Wang, Hui Wu, Songshan Shi, Yongjun Wang, Xiaojun Wu, Shunchun Wang
Journal: Gut Microbes (2024)

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG
Constitutional mosaicism of pathogenic variants in <i>SMARCB1</i> in a subset of patients with sporadic rhabdoid tumors
Authors: Lara S Fleischmann, Karolina Nemes, Selina Glaser, Alexandra G Kouroukli, Matej Boros, Susanne Bens, Sonja Dahlum, Helene Kretzmer, Florian Oyen, Joachim Gerss, Martin Hasselblatt, Michael C Frühwald, Reiner Siebert
Journal: Neuro-Oncology (2024)

Abstract Background Malignant rhabdoid tumors (RT) are aggressive malignancies predominantly affecting very young children. The characteristic genetic alteration is the biallelic inactivation of SMARCB1. In approximately 30% of patients, one SMARCB1 allele is constitutionally altered conferring a particularly unfavorable prognosis. Constitutional mosaicism for pathogenic SMARCB1 mutations has recently been reported in distinct cases of allegedly sporadic RT. We aimed to systematically investigate the frequency and clinical impact of constitutional mosaicism in patients with sporadic RT included in the EU-RHAB registry. Methods We selected 29 patients with RT displaying at least one pathogenic small variant in SMARCB1 in the tumor DNA and the absence of a germline mutation. We re-screened blood-derived patients and controlled DNA for the respective small variant by polymerase chain reaction with unique molecular identifiers and ultra-deep next-generation sequencing. Clinical data in patients with and without mosaicism and 174 EU-RHAB controls were compared. Results Employing an ultra-deep sequencing approach, we detected tumor-associated SMARCB1 variants in blood-derived DNA in 9/29 patients. In 6/29 patients (21%), whose variant allele frequency (VAF) exceeded 2%, constitutional mosaicism was assumed whereas tumor DNA contamination was documented in 1/3 of patients with VAF below 1%. No significant differences were observed between 6 mosaic-positive and 20 -negative patients regarding age at diagnosis, presence of metastases, event-free or overall survival. Conclusions Constitutional mosaicism for pathogenic small SMARCB1 variants is recurrent in patients with allegedly sporadic RT. The clinical implications of such variants need to be determined in larger, prospective cohorts also including detection of structural variants of SMARCB1.