Incidence,risk factors and outcome of acute kidney injury (AKI) in patients with COVID-19

Clinical and Experimental Nephrology - Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and...     

A recurrent homozygous LMNA missense variant p.Thr528Met causes atypical progeroid syndrome characterized by mandibuloacral dysostosis,severe muscular dystrophy,and skeletal deformities

Atypical progeroid syndromes (APS) are premature aging syndromes caused by pathogenic LMNA missense variants, associated with unaltered expression levels of lamins A and C, without accumulation of wild-type or deleted prelamin A isoforms, as observed in Hutchinson-Gilford progeria syndrome (HGPS) or HGPS-like syndromes. A specific LMNA missense variant, (p.Thr528Met), was previously identified in a compound heterozygous state in patients affected by APS and severe familial partial lipodystrophy, whereas heterozygosity was recently identified in patients affected by Type 2 familial partial lipodystrophy. Here, we report four unrelated boys harboring homozygosity for the p.Thr528Met, variant who presented with strikingly homogeneous APS clinical features, including osteolysis of mandibles, distal clavicles and phalanges, congenital muscular dystrophy with elevated creatine kinase levels, and major skeletal deformities. Immunofluorescence analyses of patient-derived primary fibroblasts showed a high percentage of dysmorphic nuclei with nuclear blebs and typical honeycomb patterns devoid of lamin B1. Interestingly, in some protrusions emerin or LAP2α formed aberrant aggregates, suggesting pathophysiology-associated clues. These four cases further confirm that a specific LMNA variant can lead to the development of strikingly homogeneous clinical phenotypes, in these particular cases a premature aging phenotype with major musculoskeletal involvement linked to the homozygous p.Thr528Met variant.     

In vivo imaging of neuroinflammation

We briefly outline the rationale for employing positron emission tomography (PET), using the ligand [¹¹C](R)-PK11195, the binding site for which is highly expressed by activated microglia, in order (a) to detect in vivo neuroinflammatory changes occurring in a variety of brain diseases and at different disease stages and (b) to monitor the progression of neuroinflammation as a generic in vivo marker of ‘disease activity’. The use of [¹¹C](R)-PK11195 PET is described as a systematic attempt at measuring the emerging phenomenology of tissue pathology itself—as opposed to measuring, for example, the loss of neuronal function or structure—and as a proof of principle for the clinical utility of imaging glial cells in vivo.     

Serial versus isolated assessment of clinical and instrumental parameters in heart failure: prognostic and therapeutic implications

Background

In heart failure (HF), it is not known whether analysis of serial changes in prognostic parameters provides incremental information with respect to comprehensive isolated clinical and instrumental assessments.

Methods

We analyzed time-related changes in a period ≥6 months in a broad panel of clinical and instrumental (electrocardiographic, echocardiographic, hemodynamic, and cardiopulmonary) parameters in 105 patients with HF (age, 53 ± 10 years; 88% men; 55% New York Heart Association classification III-IV; EF, 24% ± 6%).

Results

Among the time-related parameters, QRS widening (adjusted RR per 10 ms, 1.21; 95% CI, 1.10-1.48; P = .003) and peak oxygen uptake (pVO2) decrease (adjusted RR per mL/Kg/min, 1.11; 95% CI, 1.01-1.22; P = .034) provided independent, incremental information for predicting cardiac death/need for heart transplantation (CD/HT) with respect to the entire panel of isolated readings. The overall rate of CD/HT-free survival after 12 months was 60% ± 5%. Patients who were clinically stable with QRS widening and pVO2 decrease values of <10% had a better CD/HT event-free survival rate at 1 year (92% ± 5% vs 50% ± 6%; P <.001).

Conclusions

This study indicates that analysis of time-related changes in prognostic parameters provides relevant incremental prognostic information and may help in the risk stratification of patients with HF and the selection of candidates for HT. In particular, patients who were clinically stable and had QRS widening and a pVO2 decreases <10% in a period ≥6 months appear to be characterized by a good prognosis and may not be suitable candidates for HT.     

Metabolic syndrome affects cardiovascular risk profile and response to treatment in hypertensive postmenopausal women

Metabolic syndrome is increasingly recognized as an important cardiovascular risk factor in hypertension, but its influence on the cardiovascular risk profile in hypertensive postmenopausal women has not been studied. The aim of the present study was to investigate the impact of metabolic syndrome on the cardiovascular risk profile and the response to treatment. We enrolled 350 hypertensive postmenopausal women, 55+/-6 years of age (range 47 to 60 years of age). Patients were divided into 2 groups according to the presence of metabolic syndrome. Compared with those without, women with metabolic syndrome had higher waist circumference, body mass index, and levels of glucose, triglycerides, and HDL cholesterol, as would be expected, based on definition. In addition, patients with metabolic syndrome had a cardiovascular risk profile less favorable, characterized by a significantly higher highly sensitive C-reactive protein (2.2+/-0.6 versus 1.7+/-0.7 ng/L; P<0.01), a more compromised endothelial function (flow-mediated vasodilation 2.4+/-2.2 versus 4.4+/-2.5%; P=0.01), and a significantly higher left ventricular mass (44+/-15 versus 41+/-16 g/m(2.7)). Also, antihypertensive treatment induced a more modest improvement of both endothelial dysfunction and subclinical inflammation in women with metabolic syndrome. The results of our study show that in postmenopausal women, there are 2 different forms of hypertension: that which is isolated, and that which is associated with metabolic syndrome. This last form is related to a more severe risk profile, and response to therapy is less favorable.     

Critical subaortic stenosis due to fibromuscular ridge in a 66-year-old woman: 2D-3D echocardiography findings

Subvalvular aortic stenosis (SAS) can be either a fixed stenosis resulting from subaortic anatomical obstacle or a dynamic stenosis because of hypertrophic cardiomyopathy. Here, we report a patient with a rare subaortic circumferential fibromuscular tunnel who became unusually symptomatic in her sixth decade of life. Transthoracic and mostly transesophageal echocardiography with 3D application is the preferred diagnostic modality. Indications for surgery include symptoms and LVOT gradient of 50 mm Hg. Our purpose is an image focus on this infrequent case.     

Italian version of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS): validation and longitudinal performance

Objective

To validate an Italian version of the Rasch-Built Overall ALS Disability Scale (ROADS) in a broad population of patients and assess its longitudinal performance over time.

Methods

270 ALS patients referring to the Motor Neuron Disease Clinic of the University of Padova and Modena (Italy) accepted to compile the Italian version of the ROADS and results were correlated with the ALSFRSr and ALSAQ-40 scores, FVC values, and creatinine or albumin blood levels. To verify test–retest reliability, patients were asked to fill in a second copy of the scale within 5–7 days. Thirty-nine patients compiled a further copy of questionnaire during the follow up visit (after 133 days on average) which allowed us a longitudinal assessment of the scale.

Results

We found a good external construct validity between ROADS and either ALSFRS-R (correlation coefficient = 0.85) or ALSAQ-40 (correlation coefficient = − 0.84). Test–retest reliability was excellent with a concordance-correlation coefficient of 0.93. Yet, we observed a significant correlation between changes over time of the ROADS normalised sum score (− 2.18 point loss per month) and those of both the ALSFRS-R (positive correlation; Rho = 0.64, p ≤ 0.0001) or the ALSAQ-40 (negative correlation; Rho = − 0.60, p = 0.014).

Conclusions

The Italian version of ROADS proved to be a reliable marker to monitor overall disability in ALS patients. Further studies are necessary to assess its longitudinal performance.