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OBJECTIVE: In this study, we aimed to evaluate the kidney involvement assessed by estimated glomerular filtration rate (eGFR), the associations with specific clinical disease variables and laboratory findings, and the predictive role of eGFR on clinical outcomes of patients admitted with COVID-19 in Internal Medicine ward in the first wave. PATIENTS AND METHODS: Clinical data of 162 consecutive patients hospitalized in the University Hospital Policlinico Umberto I in Rome, Italy, between December 2020 to May 2021 were collected and retrospectively analyzed. RESULTS: The median eGFR was significantly lower in patients with worse outcomes than in patients with favorable outcomes [56.64 ml/min/1.73 m2 (IQR 32.27-89.73) vs. 83.39 ml/min/1.73 m2 (IQR 69.59-97.08), p<0.001]. Patients with eGFR < 60 ml/min/1.73 m2 (n=38) w ere s ignificantly o lder c ompared to patients with normal eGFR [82 years (IQR 74-90) vs. 61 years (IQR 53-74), p<0.001] and they had fever less frequently [39.5% vs. 64.2%, p<0.01]. Kaplan-Meier curves demonstrated that overall survival was significantly shorter in patients with eGFR < 60 ml/min/1.73 m2 (p<0.001). In multivariate analysis, only eGFR < 60 ml/min/1.73 m2 [HR=2.915 (95% CI=1.110-7.659), p<0.05] and platelet to lymphocyte ratio [HR=1.004 (95% CI=1.002-1.007), p<0.01] showed a significant predictive value for death or transfer to intensive care unit (ICU). CONCLUSIONS: Kidney involvement on admission was an independent predictor for death or transfer to ICU among hospitalized COVID-19 patients. The presence of chronic kidney disease could be regarded as a relevant factor in risk stratification for COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Increased serum uric acid (SUA) levels are found in cardiovascular and kidney diseases, associated with the development of vascular injury. Uric acid stimulates the inflammatory pathways, promotes vascular smooth muscle cells proliferation, activates renin-angiotensin system leading to the development and progression of vascular damage. Renal function-normalized uric acid [SUA to serum creatinine ratio (SUA/SCr)] has been suggested to be a better indicator of uric acid., Aim: To investigate the correlation between SUA level and SUA/SCr in the development of chronic and vascular lesions (CVL) in patients with primary glomerulonephritis (GN)., Methods: A retrospective observational study was conducted in 95 consecutive renal native biopsies performed at Policlinico Umberto I of Rome (Italy). Patient inclusion criteria were age ≥ 18 years, a renal biopsy confirming diagnosis of primary GN, the availability of complete demographic, clinical, pathological, and laboratory data., Results: Median SCr was 1.06 mg/dl (IQR 0.77;1.70) with a median eGFR of 70.40 ml/min (IQR 40.40;105). Median SUA was 5.90 mg/dl (IQR 4.30;6.90) and median SUA/SCr was 4.70 (IQR 3.20;6.80). CVL were reported in 56 (58.9%) patients. Median SUA/SCr was significantly lower in patients with CVL than patients without CVL [3.95 (IQR 2.65;6) vs 5.90 (IQR 4.30;7.20), p<0.01]. Logistic regression analysis showed that SUA/SCr ≤ 4.05 [OR 5.451 (95% CI 1.222;24.325), p<0.05] was independently associated with CVL., Conclusions: CVL play a crucial role in the progression of kidney disease. SUA/SCr ≤ 4.05 is associated with CVL in patients with primitive GN., Competing Interests: Declarations. Conflict of interest: No conflict of interest to declare., (© 2024. The Author(s).)

Introduction: Serum uric acid (SUA), the final product of purine metabolism, is an independent risk factor for cardiovascular (CV) disease. Since SUA levels depend on renal function, SUA to serum creatinine ratio (SUA/sCr) is emerging as a more specific biomarker of CV risk., Aim: To evaluate in hospitalized patients with cardiorenal multimorbidity (CRM) if the SUA/sCr ≥ 5.35 is associated with clinical outcomes. The primary outcome was in-hospital mortality. The secondary outcome was the composite of all-cause of mortality and adverse clinical events., Methods: We conducted a retrospective review of medical records from consecutive CRM inpatients admitted to the medical ward. The composite endpoint was calculated as all-cause mortality and adverse clinical events such as acute coronary syndrome, stroke, infections, and renal replacement therapy., Results: In our cohort, 141 patients (mean age of 75.6 ± 10.2 years) were identified with CRM. In-hospital mortality occurred in 17 patients (16%), and 64 patients (60.4%) experienced adverse clinical outcomes. Among the 106 patients, 20 (18.9%) had an SUA/sCr ≥ 5.35, while 86 (81.1%) had an SUA/sCr < 5.35. Male gender was significantly associated with SUA/sCr ≥ 5.35 (p = 0.007). In-hospital mortality was significantly higher in patients with SUA/sCr ≥ 5.35 (p = 0.010), and a positive correlation with adverse clinical outcomes was documented in this subgroup (p = 0.012)., Conclusion: in patients with CRM, SUA/sCr ≥ 5.35 is associated with increased in-hospital mortality and worse clinical outcomes. The ratio and related cut-off value of SUA/sCr could represent a useful biomarker to assess in-hospital complications in CRM patients., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest regarding this study., (© 2025. The Author(s).)

Patients with hematological malignancies (HMs) are at higher risk of severe COVID-19 and secondary infections, which further complicate their outcomes. This study evaluated the impact of secondary infections (SIs) on mortality in hospitalized HM patients with SARS-CoV-2 infection and identified risk factors associated with SIs. We included 217 patients with HMs and COVID-19 admitted to a tertiary hospital in Rome, from April 2020 to September 2022. SIs occurred in 44.2% of patients, with bloodstream infections (42.7%) and respiratory infections (30.5%) being most frequent; among the latter, COVID-19-associated pulmonary aspergillosis (CAPA) was observed in 41.4% of cases. Viral reactivations, predominantly CMV, occurred in 9.2% of patients. The overall mortality rate was 29%, with higher mortality observed in patients with SIs (47.4% vs. 14.7%, p < 0.01). Risk factors for SIs included severe COVID-19 (OR = 2.957, p < 0.05) and prolonged hospitalization (OR = 1.095, p < 0.001). Severe COVID-19 (OR = 8.229, p < 0.001), intensive care unit (ICU) admission (OR = 15.232, p < 0.001), chronic steroid therapy (OR = 2.803, p < 0.05), SIs (OR = 2.892, p < 0.05), and viral reactivation (OR = 6.269, p < 0.01) were independent predictors of mortality. SIs and viral reactivations are common in patients with HMs and SARS-CoV-2 infection and significantly increase mortality, highlighting the need for timely management and preventive strategies in this vulnerable population.

Objective: The aim of the study was to evaluate the association between the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio and estimated glomerular filtration rate (eGFR) and their association with mortality in the European Scleroderma Trials and Research (EUSTAR) cohort., Methods: Patients with systemic sclerosis (SSc) from the EUSTAR database with TAPSE, sPAP, and parameters required to calculate eGFR were included. Logistic regression and Cox regression analysis were performed to evaluate TAPSE/sPAP as a risk factor for chronic kidney disease (CKD) and overall survival., Results: A total of 2,370 patients with SSc were included; 284 (12%) patients had CKD stage 3a-5. TAPSE/sPAP (odds ratio [OR] 0.479; 95% CI 0.310-0.743; P < 0.001), arterial hypertension (OR 3.118; 95% CI 2.173-4.475; P < 0.001), diastolic dysfunction (OR 1.670; 95% CI 1.148-2.428; P < 0.01), and N-terminal pro-B-type natriuretic peptide (OR 1.165; 95% CI 1.041-1.304; P < 0.01) were associated with CKD stage 3a-5. TAPSE/sPAP ≤0.32 mm/mm Hg (hazard ratio [HR] 3.589; 95% CI 2.236-5.761; P < 0.001), eGFR <60 mL/min per 1.73 m 2 (HR 2.818; 95% CI 1.777-4.468; P < 0.001), and age (HR 1.782; 95% CI 1.348-2.356; P < 0.001) were the most significant predictive factors for all-cause mortality. A total of 276 patients with SSc had pulmonary hypertension (PH) confirmed by right-sided heart catheterization, with 69 (25%) having CKD stage 3a-5. No difference was found in eGFR between patients with PH with reduced or normal cardiac index., Conclusion: Reduced TAPSE/sPAP ratio is independently associated with CKD. TAPSE/sPAP ratio ≤0.32 mm/mm Hg and eGFR <60 mL/min per 1.73 m 2 are prognostic factors for all-cause mortality. In patients with SSc with PH, eGFR is independent by reduced cardiac output., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Alzheimer's disease is a disabling neurodegenerative disorder for which no effective treatment currently exists. To predict the diagnosis of Alzheimer's disease could be crucial for patients' outcome, but current Alzheimer's disease biomarkers are invasive, time consuming or expensive. Thus, developing MRI-based computational methods for Alzheimer's disease early diagnosis would be essential to narrow down the phenotypic measures predictive of cognitive decline. Amnestic mild cognitive impairment (aMCI) is associated with higher risk for Alzheimer's disease, and here, we aimed to identify MRI-based quantitative rules to predict aMCI to possible Alzheimer's disease conversion, applying different machine learning algorithms sequentially. At baseline, T1-weighted brain images were collected for 104 aMCI patients and processed to obtain 146 volumetric measures of cerebral grey matter regions [regions of interest (ROIs)]. One year later, patients were classified as converters (aMCI-c = 32) or non-converters, i.e. clinically and neuropsychologically stable (aMCI-s = 72) based on cognitive performance. Feature selection was performed by random forest (RF), and the identified seven ROIs volumetric data were used to implement support vector machine (SVM) and decision tree (DT) classification algorithms. Both SVM and DT reached an average accuracy of 86% in identifying aMCI-c and aMCI-s. DT found a critical threshold volume of the right entorhinal cortex (EC-r) as the first feature for differentiating aMCI-c/aMCI-s. Almost all aMCI-c had an EC-r volume <1286 mm 3 , while more than half of the aMCI-s patients had a volume above the identified threshold for this structure. Other key regions for the classification between aMCI-c/aMCI-s were the left lateral occipital (LOC-l), the middle temporal gyrus and the temporal pole cortices. Our study reinforces previous evidence suggesting that the morphometry of the EC-r and LOC-l best predicts aMCI to Alzheimer's disease conversion. Further investigations are needed prior to deeming our findings as a broadly applicable predictive framework. However, here, a first indication was derived for volumetric thresholds that, being easy to obtain, may assist in early identification of Alzheimer's disease in clinical practice, thus contributing to establishing MRI as a useful non-invasive prognostic instrument for dementia onset., Competing Interests: The authors report no competing interests., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.)

To investigate the potential contribution of chest wall muscle area (CWMA) to the ventilatory efficiency and exercise capacity in patients with Systemic Sclerosis (SSc) without interstitial lung disease (ILD). Forty-four consecutive SSc patients [F = 37, median age 53.5 years (IQR 43.5-58)] were examined using chest high-resolution computed tomography (HRCT), pulmonary function tests and cardiopulmonary exercise testing (CPET). The CWMA was evaluated at the level of the ninth thoracic vertebra on CT images by two independent evaluators blinded to the patient information. CPET parameters analyzed were maximum oxygen uptake (VO2 max) and VO2 at anaerobic threshold (VO 2 @AT); minute ventilation (VE); maximum tidal volume (VT). A statistically significant positive correlation was found between CWMA and maximum workload (r = 0.470, p < 0.01), VO2 max ml/min (r = 0.380, p < 0.01), VO2@AT (r = 0.343, p < 0.05), VE (r = 0.308, p < 0.05), VT (r = 0.410, p < 0.01) and VO2/heart rate (r = 0.399, p < 0.01). In multiple regression analysis, VO2 max (ml/min) was significantly associated with CWMA [β coefficient = 5.226 (95% CI 2.824, 7.628); p < 0.001], diffusing capacity for carbon monoxide (DLco) [β coefficient = 6.749 (95% CI 1.460, 12.039); p < 0.05] and body mass index (BMI) [β coefficient = 41.481 (95% CI 8.802, 74.161); p < 0.05]. In multiple regression analysis, maximum workload was significantly associated with CWMA [β coefficient = 0.490 (95% CI 0.289, 0.691); p < 0.001], DLco [β coefficient = 0.645 (95% CI 0.202, 1.088); p < 0.01] and BMI [β coefficient = 3.747 (95% CI 1.013, 6.842); p < 0.01]. In SSc-patients without ILD, CWMA represents an important variable in exercise capacity and can be evaluated by the mediastinal window available in the HRCT images required for lung disease staging., Competing Interests: Declarations. Conflict of interest: The authors declare that this research was conducted without commercial or financial relationships that could represent a potential conflict of interest. Ethical approval and Informed consent: This study was approved by the Ethics Committee of Sapienza University (IRB 0304) and written informed consent was obtained from all patients. Human and animal rights statement: The present study was conducted according to the Declaration of Helsinki (1964) and its later amendments., (© 2024. The Author(s).)

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4-5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration., Competing Interests: Competing interests The authors declare no competing interests related to this article. B.A.G. provides consulting services for Natera, Inc. D.J.S. has received consultancy honoraria in the past 3 years from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. P.S. reports personal fees from Bial, AbbVie, and Boston Scientific. G.G. owns stocks in Koios Care (https://www.koios.care/) and has received consultancy fees from Abbvie Belgium, Zambon Belgium, and EG Belgium (Stada group). He also received an Honorarium from Abbvie Belgium, Zambon Belgium, and EG Belgium. J.W. has received Honoraria from the Movement Disorders Society. K.P. owns stocks in Amprion and Curasen. She has also received honoraria from invited scientific presentations to universities and professional societies not exceeding $5000/yr and provides consulting services to Curasen. J.K. has received Honoraria from Ipsen and Merz. Y.D.v.d.W. has received a speaker’s fee for postdoctoral training organized by Medilex and AbbVie., (© 2024. The Author(s).)

Background: The 2022 European Society of Cardiology/European Respiratory Society guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery pressure (mPAP) > 20 mm Hg at right heart catheterization (RHC). Previously, patients with an mPAP between 21 and 24 mm Hg were classified in a "gray zone" of unclear clinical significance., Research Question: What is the diagnostic performance of the main parameters used for PH screening in detecting patients with systemic sclerosis (SSc) with an mPAP of 21 to 24 mm Hg at RHC?, Study Design and Methods: Patients with SSc from the European Scleroderma Trials and Research (EUSTAR) database with available tricuspid annular plane systolic excursion (TAPSE), systolic PAP (sPAP), and mPAP data were included. Patients with mPAP 21 to 24 mm Hg and patients with mPAP ≤ 20 mm Hg were considered for the analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated., Results: TAPSE/sPAP was lower in the group of patients with SSc with mPAP 21 to 24 mm Hg than in the non-PH group (0.58 [0.46-0.72] vs 0.69 [0.57-0.81] mm/mm Hg, respectively; P < .01). No difference was found in other parameters between the two groups. Diffusing capacity of the lungs for carbon monoxide < 80% of the predicted value had the highest sensitivity (88.9%) and NPV (80%), but the lowest specificity (18.2%) and PPV (30.8%) in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity (78.9%), PPV (50%), and accuracy (68.1%); its NPV was 75.4%, and its sensitivity was 45.1%., Interpretation: In this study, diffusing capacity of the lungs for carbon monoxide < 80% of the predicted value was the parameter with the highest sensitivity and NPV in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity, PPV, and accuracy and, therefore, can be a useful additional parameter to decrease the number of unnecessary RHCs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: V. S. is senior clinical investigator of the Research Foundation—Flanders (Belgium): (FWO) (1.8.029.20N). This funding source had no role in the literature review and the synthesis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication. C. B. received grants from Boehringer-Ingelheim, consulting fees from Janssen, honoraria for lectures from Novartis, and travel grants from Kyverna, which were not related to this project. E. Z. received speaking and lecture fees from Janssen and consulting fees from Janssen and GSK. F. I. received honoraria and speaking fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB outside this work. C. P. S. A. received consulting fees and support for attending meetings from Janssen-Cilag SAS, Boehringer Ingelheim Ltd and MSD. None declared (A. C., E. H., C. P., G. R., J. H., D. L., A. M., A. M. G., M.-E. T., S. O., M. V., F. D. G., E. R.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score "moderate-to-very severe" [OR 1.001 (CI 95%: 1.001-1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023-1.506), p < 0.05] as variables associated with UCLA distension/bloating "moderate-to-very severe". The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea "moderate-to-very severe" [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms., (© 2024. The Author(s).)

Objective: To estimate the prevalence of temporomandibular dysfunction in scleroderma patients according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and to correlate it with disease variables., Methods: Temporomandibular dysfunction was evaluated in 75 scleroderma patients and 74 healthy controls using DC/TMD. Gastrointestinal symptoms were evaluated through the University of California Los Angeles (UCLA) score in scleroderma patients., Results: There was no difference of prevalence in temporomandibular dysfunction [30 (40%) vs 30 (40.5%); p > 00.05] between scleroderma patients and healthy controls. Scleroderma patients had a significant reduction in all oral movements compared to healthy controls. Scleroderma patients with temporomandibular dysfunction had a statistically higher score in the UCLA distention/bloating item [1.75 (0.5-2.38) vs 0.75 (0.25-1.75); p < 0.05] than scleroderma patients without temporomandibular dysfunction., Discussion: Temporomandibular dysfunction prevalence between scleroderma patients and healthy controls is similar. In scleroderma patients, temporomandibular dysfunction reduces oral mobility and opening, which worsens distension/bloating.

Background: Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs., Methods: 75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI)., Results: The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels., Conclusion: TSLP might have a key role in digital microvascular damage of SSc patients., Competing Interests: Declaration of competing interest All the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)