Biological Rhythms and Psychosocial Functioning in Depression: An Exploratory Analysis Informed by a Mediation Model

Background. Major Depressive Disorder (MDD) is a highly prevalent and disabling condition frequently accompanied by cognitive deficits, impaired psychosocial functioning, and biological rhythm disturbances. Despite extensive literature on individual associations between depression and circadian disruptions, the mediating role of biological rhythms in the functional outcomes of MDD remains underexplored. Objectives. This study aimed to explore the associations between depression severity, biological rhythms, sleep quality, and psychosocial functioning, and to assess whether biological rhythm disturbances mediate the impact of depression on functioning. Methods. Sixty-one inpatients diagnosed with moderate-to-severe MDD were assessed using standardized instruments: BDI-II for depressive symptoms, BRIAN for biological rhythms, PSQI for sleep quality, and FAST for global functioning. Group comparisons, non-parametric correlations, and a mediation analysis were conducted to test direct and indirect effects. Results. Participants showed severe depressive symptoms, impaired functioning, disrupted biological rhythms, and poor sleep. Women reported more depressive episodes, reduced autonomy, and worse sleep than men. Depression severity was associated with circadian and sleep disturbances, which in turn related to functional impairment. Mediation analysis suggested that biological rhythms partially mediate the impact of depression on functioning. Conclusions. Findings from this preliminary analysis suggest that biological rhythm disturbances may play a mediating role in the relationship between depressive symptoms and daily psychosocial functioning. While not conclusive, these results highlight the potential relevance of chronobiological factors in understanding functional outcomes in MDD. Further research using longitudinal and controlled designs is needed to clarify these associations and their clinical implications.</p

The COVID-19 Assessment for Survival at Admission (CASA) Index: A 12 Months Observational Study

Objective: Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the stratification of patients at risk of mortality is not well defined. In this study, we aimed to define a mortality risk index to allocate patients to the appropriate intensity of care. Methods: This is a 12 months observational longitudinal study designed to develop and validate a pragmatic mortality risk score to stratify COVID-19 patients aged ≥18 years and admitted to hospital between March 2020 and March 2021. Main outcome was in-hospital mortality. Results: 244 patients were included in the study (mortality rate 29.9%). The Covid-19 Assessment for Survival at Admission (CASA) index included seven variables readily available at admission: respiratory rate, troponin, albumin, CKD-EPI, white blood cell count, D-dimer, Pa02/Fi02. The CASA index showed high discrimination for mortality with an AUC of 0.91 (sensitivity 98.6%; specificity 69%) and a better performance compared to SOFA (AUC = 0.76), age (AUC = 0.76) and 4C mortality (AUC = 0.82). The cut-off identified (11.994) for CASA index showed a negative predictive value of 99.16% and a positive predictive value of 57.58%. Conclusions: A quick and readily available index has been identified to help clinicians stratify COVID-19 patients according to the appropriate intensity of care and minimize hospital admission to patients at high risk of mortality

Case Report: Rapid renal response to venetoclax monotherapy in a CLL patient with secondary membranous glomerulonephritis

Membranous glomerulonephritis (MGN) is a rare extra-hematological autoimmune complication of chronic lymphocytic leukemia (CLL), clinically characterized by nephrotic-range proteinuria and, less frequently, renal failure. Because of the rarity of this condition, there is no standardized treatment. Chlorambucil and fludarabine-based regimens, possibly combined with rituximab, have been historically the most frequent therapeutic approaches, with renal response obtained in about two-third of the patients. However, responses are often transient and partial. Here we describe the first patient with rituximab-refractory, CLL-related MGN successfully treated with the Bcl-2 antagonist venetoclax. Nephrotic syndrome resolved as soon as three months after venetoclax initiation, with no unexpected toxicities. At the last follow-up, 17 months after venetoclax start, renal response persists, with proteinuria below 0.5 g/24 hours. This case suggests that targeted agents, particularly Bcl-2 antagonists, might be suitable options for patients with renal autoimmune disorders arising in the context of CLL

Prognostic Value of Glomerular Collagen IV Immunofluorescence Studies in Male Patients with X-Linked Alport Syndrome

Background and objectives X-linked Alport syndrome (X-AS) is caused by mutations of the COL4A5 gene, which encodes for the collagen IV a5 chain (a5[COLIV]), resulting in structural and functional abnormalities of the glomerular basement membrane (GBM) and leading to CKD. The aim of the present study was to evaluate the prognostic value of residual collagen IV chain expression in the GBM of patients with X-AS. Design, setting, participants, &amp; measurements The medical records of 22 patients with X-AS from 21 unrelated families collected between 1987 and 2009 were reviewed (median age at last follow-up, 19.9 years; range, 5.4-35.1 years); GBM expression of a1, a3, and a5(COLIV) chains was assessed by immunofluorescence microscopy. Results GBM distribution of the a5(COLIV) chain was diffuse in 1 and segmental or absent in 21 of the 22 patients; the expression of the a3(COLIV) chain was diffuse in 5 of 22 patients and segmental or absent in 17 of 22 patients. Patients with diffuse staining for the a3(COLIV) chain presented with proteinuria significantly later (median age, 16.9 versus 6.1 years; P=0.02) and reached an estimated GFR &lt; 90 ml/min per 1.73 m2 at an older age (median age, 27.0 versus 14.9 years; P=0.01) compared with patients with segmental or absent staining. Two thirds of patients with abnormal a3(COLIV) expression by immunofluorescence studies had null or truncating COL4A5 mutations, as opposed to none of the 4 tested patients with diffuse a3(COLIV) chain glomerular distribution. © 2013 by the American Society of Nephrology

Choroidopathy in patients with systemic lupus erythematosus with or without nephropathy

The aim of this study was to evaluate indocyanine green angiographic findings in patients with systemic lupus erythematosus (SLE) with or without lupus nephritis. In particular, the presence of choroidal abnormalities at indocyanine green angiography (ICG-A) that could not be detected by fluorescein angiography (FAG) was investigated. METHODS: Sixteen patients with SLE underwent simultaneous ICG-A and FAG. Patients were divided into 2 groups based on whether renal disease was present (group A, n=9) or not (group B, n=7). RESULTS: Drusen-like deposits were ophthalmoscopically evident in only 1 out of 9 group A patients (11.1%). While FAG disclosed the deposits in 4 out of 9 group A patients (44.4%), drusen-like deposits were otherwise found in all group A patients (100%) by ICG-A. FAG and ICG-A did not show choroidal alterations in group B patients. CONCLUSIONS: ICG-A can provide information that is not detectable by clinical or FAG examination in patients with lupus nephritis (group A). The findings of choroidopathy by ICG-A represent an indicator of ocular involvement and could be an indirect sign of renal involvement. Given that histological lesions may be present where there are no anomalies in urinary sediment and/or proteinuria, the positivity of ICG-A could help in deciding whether or not to carry out a renal biopsy. Therefore, ICG-A could be useful in the screening of patients with SLE, especially where there are no evident signs of renal involvemen

Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience

Abstract Aims To evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy. Methods Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12 months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2. Patients were defined as responders if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at their last follow-up visit. Results Forty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9 mmHg and 155.2/86.5 ± 20.9/14.0 mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by − 19.7 ± 27.1 mmHg and by − 13.9 ± 23.6 mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR &lt; 45 mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12 months), even in patients with the lowest eGFR values at baseline. Conclusion RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12 months. Graphic abstract </jats:sec

Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience

Aims: To evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy. Methods: Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12&nbsp;months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45&nbsp;mL/min/1.73&nbsp;m2. Patients were defined as responders if systolic BP decreased by at least 5&nbsp;mmHg at ambulatory BP or by 10&nbsp;mmHg at office BP at their last follow-up visit. Results: Forty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9&nbsp;mmHg and 155.2/86.5 ± 20.9/14.0&nbsp;mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by - 19.7 ± 27.1&nbsp;mmHg and by - 13.9 ± 23.6&nbsp;mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR &lt; 45&nbsp;mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E' at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12&nbsp;months), even in patients with the lowest eGFR values at baseline. Conclusion: RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12&nbsp;months

Prognostic Value of glomerular collagen IV immunofluorescence studies in male patients with X-linked alport syndrome

Background and objectives X-linked Alport syndrome (X-AS) is caused by mutations of the COL4A5 gene, which encodes for the collagen IV a5 chain (a5[COLIV]), resulting in structural and functional abnormalities of the glomerular basement membrane (GBM) and leading to CKD. The aim of the present study was to evaluate the prognostic value of residual collagen IV chain expression in the GBM of patients with X-AS. Design, setting, participants, &amp; measurements The medical records of 22 patients with X-AS from 21 unrelated families collected between 1987 and 2009 were reviewed (median age at last follow-up, 19.9 years; range, 5.4-35.1 years); GBM expression of a1, a3, and a5(COLIV) chains was assessed by immunofluorescence microscopy. Results GBM distribution of the a5(COLIV) chain was diffuse in 1 and segmental or absent in 21 of the 22 patients; the expression of the a3(COLIV) chain was diffuse in 5 of 22 patients and segmental or absent in 17 of 22 patients. Patients with diffuse staining for the a3(COLIV) chain presented with proteinuria significantly later (median age, 16.9 versus 6.1 years; P=0.02) and reached an estimated GFR &lt; 90 ml/min per 1.73 m2 at an older age (median age, 27.0 versus 14.9 years; P=0.01) compared with patients with segmental or absent staining. Two thirds of patients with abnormal a3(COLIV) expression by immunofluorescence studies had null or truncating COL4A5 mutations, as opposed to none of the 4 tested patients with diffuse a3(COLIV) chain glomerular distribution. © 2013 by the American Society of Nephrology