Miracle-dz/UniFAR-FTUs huggingface dataset:
Remission of lupus nephritis: the trajectory of histological response in successfully treated patients

Objective This study investigated changes in kidney histology over time in patients with lupus nephritis (LN) undergoing immunosuppressive treatment. Methods Patients with proliferative±membranous LN were studied. After a diagnostic kidney biopsy (Bx1), patients had protocol biopsy 2 (Bx2) at 9 (6–15) months and protocol biopsy 3 (Bx3) at 42 (28–67) months. Kidney histological activity and chronicity indices (AI, CI) were measured. Results AI declined in a biphasic fashion, falling rapidly between Bx1 and Bx2 and then more slowly between Bx2 and Bx3. Patients were divided into those who achieved histological remission, defined as an AI=0 at Bx3 (group 1), and those with persistent histological activity (AI >0) at Bx3 (group 2). The early decline in AI was 1.6 times greater (95% CI 1.30, 1.91) in group 1 than group 2 (p=0.01). Between Bx2 and Bx3, the AI decline was 2.19-fold greater (95% CI 2.09, 2.29) in group 1 versus group 2 (p=7.34×10−5). Individual histological components of the AI resolved at different rates. Inflammatory lesions like glomerular crescents, karyorrhexis and necrosis mostly resolved by Bx2, whereas endocapillary hypercellularity, subendothelial hyaline deposits and interstitial inflammation resolved slowly, accounting for residual histological activity at biopsy 3 in group 2. In contrast, CI increased rapidly, by 0.15 units/month between Bx1 and Bx2, then plateaued. There were no differences in the rate of accumulation of chronic damage between group 1 and group 2. The increase in CI was significantly related to the severity of glomerular crescents (p=0.044), subendothelial hyaline deposits (p=0.002) and interstitial inflammation (p=0.015) at Bx1. Conclusions LN histological activity takes months to years to resolve, providing a rationale for the need of long-term, well-tolerated maintenance immunosuppression. Despite responding, LN kidneys accrue chronic damage early during treatment. This finding provides an explanation for the association of chronic progressive kidney disease with recurrent episodes of LN.
Intracytoplasmic sperm injection vs. in‐vitro fertilization in couples in whom the male partners had a semen analysis within normal reference ranges: An open debate

During recent decades, the application of intracytoplasmic sperm injection has increased considerably worldwide, especially in couples with non‐male factor infertility. However, several studies analyzing the broad use of intracytoplasmic sperm injection, even in cases with a normal semen analysis, have collectively demonstrated no benefits compared to conventional in‐vitro fertilization. Currently, there is insufficient evidence to support the intracytoplasmic sperm injection technique vs. in‐vitro fertilization in cases of poor ovarian response or a low number of oocytes collected, or in patients with advanced maternal age. Since the intracytoplasmic sperm injection technique is more operator‐dependent and invasive, its use should only be recommended in cases of male‐factor infertility. There is some evidence showing that intracytoplasmic sperm injection is linked with an increased risk of birth defects. Albeit this evidence is limited, and currently it is not possible to draw a firm conclusion on these concerns, we do believe that these risks should be rigorously investigated. Thus, this review aims to clarify the debate on the application of the intracytoplasmic sperm injection procedure, as compared to standard in‐vitro fertilization, in those assisted reproductive technology cycles without a clear male factor infertility. Furthermore, we try to clarify whether intracytoplasmic sperm injection would result in a higher live birth rate than in‐vitro fertilization, in couples with non‐male factor infertility.
Variance estimation of the risk difference when using propensity‐score matching and weighting with time‐to‐event outcomes

Observational studies are increasingly being used in medicine to estimate the effects of treatments or exposures on outcomes. To minimize the potential for confounding when estimating treatment effects, propensity score methods are frequently implemented. Often outcomes are the time to event. While it is common to report the treatment effect as a relative effect, such as the hazard ratio, reporting the effect using an absolute measure of effect is also important. One commonly used absolute measure of effect is the risk difference or difference in probability of the occurrence of an event within a specified duration of follow‐up between a treatment and comparison group. We first describe methods for point and variance estimation of the risk difference when using weighting or matching based on the propensity score when outcomes are time‐to‐event. Next, we conducted Monte Carlo simulations to compare the relative performance of these methods with respect to bias of the point estimate, accuracy of variance estimates, and coverage of estimated confidence intervals. The results of the simulation generally support the use of weighting methods (untrimmed ATT weights and IPTW) or caliper matching when the prevalence of treatment is low for point estimation. For standard error estimation the simulation results support the use of weighted robust standard errors, bootstrap methods, or matching with a naïve standard error (i.e., Greenwood method). The methods considered in the article are illustrated using a real‐world example in which we estimate the effect of discharge prescribing of statins on patients hospitalized for acute myocardial infarction.
Health Professional- and Volunteer-partnered Self-management Support (COMBO-KEY) to Promote Self-efficacy and Self-management Behaviors in People with Stroke: A Randomized Controlled Trial

Abstract Background Multiple systematic reviews have reported that self-management interventions are associated with positive impacts on self-efficacy and health-related quality of life (HRQoL) of people with stroke. Purpose This article reports the effects of an enhanced stroke self-management program. Methods Eligible adults with stroke were recruited from community-based organizations and a support group for a two-arm, assessor-blinded randomized controlled trial. Participants in the control group received usual care, while those in the intervention group also received the 8-week self-management program, Coaching Ongoing Momentum Building On stroKe rEcovery journeY (COMBO-KEY), consisting of four individual home visits and five follow-up phone calls, delivered by healthcare professionals and trained volunteers. Assessments were conducted at baseline and after the intervention, for outcomes of self-efficacy, satisfaction with the performance of self-management behaviors, HRQoL, and community reintegration, which were analyzed using generalized estimating equations (GEEs). Results 134 Participants were recruited [mean age = 64.1 years, standard deviation (SD) = 12.7]. Over 80% of the participants had a first-ever stroke [mean years after first stroke: 4.2 (SD = 5.1)]. The GEE analysis revealed that the intervention group participants showed significantly greater improvements in self-efficacy, satisfaction with their performance of self-management behaviors, HRQoL, and community reintegration at 8-week follow-up with respect to their baseline levels. Conclusions The COMBO-KEY program showed effective improvements in recovery outcomes of people with stroke. Future research should explore the inclusion of virtual/hybrid sessions, strategies to assess health conditions of people with stroke via online modes, and assessment of goal attainment and actual performance of self-management behaviors.
Citizenship status and cost‐related nonadherence in the United States, 2017–2021

Abstract Objective To assess inequities in prescription medication use and subsequent cost‐related nonadherence (CRN) and cost‐saving strategies by citizenship status in the United States. Data Sources/Study Setting National Health Interview Survey (2017–2021). Study Design This cross‐sectional study examined noncitizen (n = 8596), naturalized citizen (n = 12,800), and US‐born citizen (n = 120,195) adults. We also examined older adults (≥65 years) separately, including noncitizens without Medicare (a group of importance given their immigration‐related barriers to health care access). Multiple mediation analysis was used to examine differences in CRN and determine whether economic, health care, and immigration factors explain observed inequities. Principal Findings Noncitizens (41.9%) were less likely to use prescription medications than naturalized (60.5%) and US‐born citizens (68.2%). Among prescription medication users, noncitizens (13.8%) were more likely to report CRN than naturalized (9.5%) and US‐born citizens (11.0%). CRN differences between noncitizens and naturalized citizens (OR 1.38, 95% CI 1.21–1.44) and between noncitizens and US‐born citizens (OR 1.23, 95% CI 1.07–1.35) were explained by insurance status and food insecurity. Only 4.9% of medication users turned to alternative therapies to lower their drug costs, but there were no substantial differences across citizenship status. More medication users requested lower‐cost prescriptions (19.0%); however, noncitizens were less likely to make these requests. Older noncitizens without Medicare, of whom 23.9% requested lower‐cost drugs, were an exception. Noncitizens (5.8%), particularly older noncitizens without Medicare (21.8%), were more likely to import their drugs than naturalized (3.5%) and US‐born citizens (1.2%). Conclusions Noncitizens experience a high burden of cost‐related barriers to prescription medications. Efforts to reduce these inequities should focus on dismantling health care and food access barriers, regardless of citizenship status.
Athlete Muscular Phenotypes Identified and Compared with High-Dimensional Clustering of Lower Limb Muscle Volume Measurements

ABSTRACT Introduction Athletes use their skeletal muscles to demonstrate performance. Muscle force generating capacity is correlated with volume, meaning that variations in sizes of different muscles may be indicative of how athletes meet different demands in their sports. Medical imaging enables in vivo quantification of muscle volumes; however, muscle volume distribution has not been compared across athletes of different sports. Purpose The goal of this work was to define “muscular phenotypes” in athletes of different sports and compare these using hierarchical clustering. Methods Muscle volumes normalized by body mass of athletes (football, baseball, basketball, or track) were compared with control participants to quantify size differences using z-scores. z-Scores of 35 muscles described the pattern of volume deviation within each athlete’s lower limb, characterizing their muscular phenotype. Data-driven high-dimensional clustering analysis was used to group athletes presenting similar phenotypes. Efficacy of clustering to identify similar phenotypes was demonstrated by grouping athletes’ contralateral limbs before other athletes’ limbs. Results Analyses revealed that athletes did not tend to cluster with others competing in the same sport. Basketball players with similar phenotypes grouped by clustering also demonstrated similarities in performance. Clustering also identified muscles with similar volume variation patterns across athletes, and principal component analysis revealed specific muscles that accounted for most of the variance (gluteus maximus, sartorius, semitendinosus, vastus medialis, vastus lateralis, and rectus femoris). Conclusions Athletes exhibit heterogeneous lower limb muscle volumes that can be characterized and compared as individual muscular phenotypes. Clustering revealed that athletes with the most similar phenotypes do not always play the same sport such that patterns of muscular heterogeneity across a group of athletes reflect factors beyond their specific sports.
Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, β=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, β=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, β=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.
Impact of sarcopenia and low muscle attenuation on outcomes of ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE The aim of this study was to examine the association of sarcopenia and low muscle attenuation with survival and other clinical outcomes in patients with ovarian cancer. MATERIALS AND METHODS Systematic search was done in PubMed, EMBASE and Scopus databases for observational studies that documented the link between sarcopenia and outcomes of interest in patients with ovarian cancer, with long-term survival as a primary outcome. Other outcomes included risk of recurrence, progression-free survival and complications. Pooled effect sizes were reported as hazards ratio (HR), relative risk ratio (RR) or weighted mean difference (WMD). Random effects model was used for the analysis. RESULTS Twenty-two studies were selected, of which all, except one, were retrospective in design. Low skeletal muscle index (SMI, indicating muscle mass) (HR 1.30, 95% CI: 1.07, 1.58) and low muscle quality (HR 1.24, 95% CI: 1.03, 1.49) were associated with poor long-term survival, but not with the risk of recurrence and progression-free survival. Both low skeletal muscle index (SMI) (RR 1.49, 95% CI: 1.13, 1.98) and low muscle quality (RR 1.99, 95% CI: 1.04, 3.79) were associated with increased risk of complications. CONCLUSIONS Both low skeletal muscle mass and low muscle quality showed significant association with poor long-term survival and an increased risk of complications. However, they do not have a significant association with the risk of recurrence and progression-free survival. There is a need for more prospective studies to confirm these associations.
A prospective survey on therapeutic inertia in psoriatic arthritis (OPTI’PsA)

Abstract Objectives Clinical inertia, or therapeutic inertia (TI), is the medical behaviour of not initiating or intensifying treatment when recommended by clinical recommendations. To our knowledge, our survey is the first to assess TI around psoriatic arthritis (PsA). Methods Eight hundred and twenty-five French rheumatologists were contacted via email between January and March 2021 and invited to complete an online questionnaire consisting of seven clinical vignettes: five cases (‘oligoarthritis’, ‘enthesitis’, ‘polyarthritis’, ‘neoplastic history’, ‘cardiovascular risk’) requiring treatment OPTImization, and two ‘control’ cases (distal interphalangeal arthritis, atypical axial involvement) not requiring any change of treatment—according to the most recent PsA recommendations. Rheumatologists were also questioned about their routine practice, continuing medical education and perception of PsA. Results One hundred and one rheumatologists completed this OPTI’PsA survey. Almost half the respondents (47%) demonstrated TI on at least one of the five vignettes that warranted treatment optimization. The complex profiles inducing the most TI were ‘oligoarthritis’ and ‘enthesitis’ with 20% and 19% of respondents not modifying treatment, respectively. Conversely, clinical profiles for which there was the least uncertainty (‘polyarthritis in relapse’, ‘neoplastic history’ and ‘cardiovascular risk’) generated less TI with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment. Conclusion The rate of TI we observed for PsA is similar to published data for other chronic diseases such as diabetes, hypertension, gout or multiple sclerosis. Our study is the first to show marked clinical inertia in PsA, and further research is warranted to ascertain the reasons behind this inertia.
IL-6–Dependent STAT3 Activation and Induction of Proinflammatory Cytokines in Primary Sclerosing Cholangitis

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with periductal inflammation and fibrosis. Genetic studies suggest inflammatory cytokines and IL-6–dependent activation of transcription factor STAT3 as pivotal steps in PSC pathogenesis. However, details of inflammatory regulation remain unclear. METHODS: We recruited 50 patients with PSC (36 with inflammatory bowel disease, 14 without inflammatory bowel disease), 12 patients with autoimmune hepatitis, and 36 healthy controls to measure cytokines in the serum, bile, and immune cell supernatant using bead-based immunoassays and flow cytometry and immunohistochemistry to analyze phosphorylation of STATs in immune cells. Finally, we analyzed cytokines and STAT3 phosphorylation of T cells in the presence of JAK1/2 inhibitors. RESULTS: In PSC, IL-6 specifically triggered phosphorylation of STAT3 in CD4+ T cells and lead to enhanced production of interferon (IFN) gamma and interleukin (IL)-17A. Phospho-STAT3–positive CD4+ T cells correlated with systemic inflammation (C-reactive protein serum levels). Combination of immunohistology and flow cytometry indicated that phospho-STAT3–positive cells were enriched in the peribiliary liver stroma and represented CD4+ T cells with prominent production of IFN gamma and IL-17A. JAK1/2 inhibitors blocked STAT3 phosphorylation and production of IFN gamma and IL-6, whereas IL-17A was apparently resistant to this inhibition. DISCUSSION: Our results demonstrate systemic and local activation of the IL-6/STAT3 pathway in PSC. Resistance of IL-17A to STAT3-targeted inhibition points to a more complex immune dysregulation beyond STAT3 activation.
Right hemicolectomy for colon cancer: does the anastomotic configuration affect short‐term outcomes?

Right hemicolectomy is a common colorectal operation for resection of cancers of the right colon. The ileocolic anastomosis may be created using a stapled end‐to‐side, stapled side‐to‐side or handsewn technique. Anastomotic leak and post‐operative bleeding are uncommon but serious causes of morbidity and mortality, while post‐operative ileus contributes to prolonged length of stay. The aim of this study was to evaluate differences in short‐term outcomes between different anastomotic configurations following right hemicolectomy for colon cancer.
Interventional Versus Conservative Strategy in Patients With Spontaneous Coronary Artery Dissections: Insights From DISCO Registry

Background: The optimal management of patients with spontaneous coronary artery dissection remains debated. Methods: Patients enrolled in the DISCO (Dissezioni Spontanee Coronariche) Registry up to December 2020 were included. The primary end point was major adverse cardiovascular events, a composite of all-cause death, nonfatal myocardial infarction, and repeat percutaneous coronary intervention (PCI). Independent predictors of PCI and medical management were investigated. Results: Among 369 patients, 129 (35%) underwent PCI, whereas 240 (65%) were medically managed. ST-segment–elevation myocardial infarction (68% versus 35%, P<0.001), resuscitated cardiac arrest (9% versus 3%, P<0.001), proximal coronary segment involvement (32% versus 7%, P<0.001), and Thrombolysis in Myocardial Infarction flow 0 to 1 (54% versus 20%, P<0.001) were more frequent in the PCI arm. In-hospital event rates were similar. Between patients treated with PCI and medical therapy, there were no differences in terms of major adverse cardiovascular events at 2 years (13.9% versus 11.7%, P=0.467), all-cause death (0.7% versus 0.4%, P=0.652), myocardial infarction (9.3% versus 8.3%, P=0.921) and repeat PCI (12.4% versus 8.7%, P=0.229). ST-segment–elevation myocardial infarction at presentation (odds ratio [OR], 3.30 [95% CI, 1.56–7.12]; P=0.002), proximal coronary segment involvement (OR, 5.43 [95% CI, 1.98–16.45]; P=0.002), Thrombolysis in Myocardial Infarction flow grade 0 to 1 and 2 (respectively, OR, 3.22 [95% CI, 1.08–9.96]; P=0.038; and OR, 3.98 [95% CI, 1.38–11.80]; P=0.009) and luminal narrowing (OR per 5% increase, 1.13 [95% CI, 1.01–1.28]; P=0.037) were predictors of PCI, whereas the 2B-angiographic subtype predicted medical management (OR, 0.25 [95% CI, 0.07–0.83]; P=0.026). Conclusions: Clinical presentation and procedural variables drive the choice of the initial therapeutic approach in spontaneous coronary artery dissection. If PCI is needed, it seems to be associated with a similar risk of short-to-mid-term adverse events compared to medical treatment. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT04415762.
Zonulin as a potential biomarker for diminished ovarian reserve: A prospective study

Objective: The purpose of this research is to investigate the relationship between zonulin levels and diminished ovarian reserve (DOR), and to evaluate the potential role of autoimmunity in the development of DOR. The study contributes to the understanding of the pathogenesis of DOR, which can be an unexpected diagnosis often associated with infertility and unpleasant physical symptoms in women. Materials and Methods: This cross-sectional study was conducted by scanning 224 patients. The demographic characteristics of the patients were recorded. Antral follicle counts of the patients were determined by ultrasound, and Anti-Mullerian hormone (AMH) levels were examined. Follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, AMH measurement, and antral follicle counts were made on the 2nd or 3rd day of menstrual bleeding. The zonulin levels of the participants were measured by the ELISA method. The patients were divided into two groups according to the presence of DOR. The patients’ demographic characteristics and hormone levels were compared between these two groups, serum zonulin levels were examined, and the relationship between other hormone parameters and zonulin was investigated. Results: When the median ages of the patients in both groups were compared, the median age of patients with DOR was 38 years, significantly higher (p<0.001) than the median age of those without DOR, which was 27 years. The median zonulin levels of both groups were compare; it was observed that it was 19.71 ng/mL in the group with DOR and 11.03 ng/mL without DOR, and a statistically significant difference was found between the zonulin levels of the patients in both groups (p<0.001). A moderate inverse correlation (p<0.001) between patients’ zonulin and AMH levels, and a moderate correlation between FSH levels (p<0.001). Conclusion: In conclusion, zonulin levels of patients with DOR were higher than women without DOR. Evaluation of zonulin levels may also be considered during the diagnosis of DOR.