Evaluation of qualitative and semi-quantitative cut offs for rapid diagnostic lateral flow test in relation to serology for the detection of SARS-CoV-2 antibodies: findings of a prospective study

There is limited information to compare the qualitative and semi-quantitative performance of rapid diagnostic tests (RDT) and serology for the assessment of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, the objective of the study was (a) to compare the efficacy of SARS-CoV-2 antibody detection between RDT and laboratory serology, trying to identify appropriate semi-quantitative cut-offs for RDT in relation with quantitative serology values and to (b) evaluate diagnostic accuracy of RDT compared to the NAAT gold standard in an unselected adult population

Heterozygosity for Neuronal Ceroid Lipofuscinosis predisposes to Bipolar Disorder

Objective: Bipolar Disorder (BD) is an heritable chronic mental disorder causing psychosocial impairment, affecting patients with depressive/manic episodes. The familial transmission of BD does not follow any of the simple Mendelian patterns of inheritance. The aim of this study is to describe a new large family with twelve affected BD members: WES was performed in eight of them, three of which were diagnosed for BD, and one was reported as a "borderline" individual. Material and methods: WES data allowed us to select variants in common between the affected subjects, once including and once excluding a "borderline" subject with moderate anxiety and traits of obsessive-compulsive disorder. Results: Results were in favor of new predisposing BD genes, electing a heterozygous missense variant in CLN6 resulting in a "borderline" phenotype that if combined with a heterozygous missense variant in ZNF92 is responsible for the more severe BD phenotype. Both rare missense changes are predicted to disrupt the protein function. Conclusions: Loss of both alleles in CLN6 causes Neuronal Ceroid Lipofuscinosis, a severe progressive neurological disorder of childhood. Our results indicate that heterozygous CLN6 carriers, previously reported as healthy, may be susceptible to bipolar disorder late in life if associated with additional variants in ZNF92

The Fall in Antibody Response to SARS-CoV-2: a Longitudinal Study of Asymptomatic to Critically Ill Patients Up to 10 Months after Recovery

The aim of this study was to assess the long-term dynamics and factors associated with the serological response against the severe acute respiratory syndrome coronavirus 2 after primary infection. A prospective longitudinal study was conducted with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) during the first wave (from March to May 2020). A total of 546 individuals were included (289 female, mean age 53.1 years), mostly with mild COVID-19 (370, 68.3%). Patients were followed for a median of 302 days (interquartile range, 186 to 311). The overall seroconversion rate within 2 months was 32% for IgM and 90% for IgG. Seroreversion was observed in 90% of patients for IgM at 4 months and in 47% for IgG at 10 months. Older age, number of symptoms at acute onset, and severity of acute COVID-19 were all independent predictors of long-term immunity both for IgM (beta, linear regression coefficient, 1.10, P = 0.001; beta 5.15 P = 0.014; beta 43.84 P = 0.021, respectively) and for IgG (beta 1.43 P < 0.001; beta 10.46 P < 0.001; beta 46.79 P, 0.001, respectively), whereas the initial IgG peak was associated only with IgG duration (beta 1.12, P < 0.001). IgM antibodies disappeared at 4 months, and IgG antibodies declined in about half of patients 10 months after acute COVID-19. These effects varied depending on the intensity of the initial antibody response, age, and burden of acute COVID-19

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Mesenchymal stem cells-derived vascular smooth muscle cells release abundant levels of osteoprotegerin

Although several studies have shown that the serum levels of osteoprotegerin (OPG) are significantly elevated in patients affected with atherosclerotic lesions in coronary and peripheral arteries, the cellular source and the role of OPG in the physiopathology of atherosclerosis are not completely defined. Therefore, we aimed to investigate the potential contribution of mesenchymal stem cells in the production/release of OPG. OPG was detectable by immunohistochemistry in aortic and coronary atherosclerotic plaques, within or in proximity of intimal vascular smooth muscle cells (SMC). In addition, bone marrow mesenchymal stem cell (MSC)-derived vascular SMC as well as primary aortic SMC released in the culture supernatant significantly higher levels of OPG with respect to MSC-derived endothelial cells (EC) or primary aortic EC. On the other hand, in vitro exposure to full-length human recombinant OPG significantly increased the proliferation rate of aortic SMC cultures, as monitored by bromodeoxyuridine incorporation. Taken together, these data suggest that OPG acts as an autocrine/paracrine growth factor for vascular SMC, which might contribute to the progression of atherosclerotic lesions

Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience

Background: Procalcitonin (PCT) is routinely used for an early recognition of severe infections and for promoting appropriate use of antibiotics. However, limited data correlating values of PCT with etiology of infection has been reported.Methods: During 2016, all positive blood cultures (BC) were retrospectively extracted in a 1100-beds Italian tertiary-care hospital. PCT and C-reactive protein (CRP) values were recorded within 24 h from BC collection. Primary endpoint of the study was to investigate the correlation between PCT and CRP values and the occurrence of bloodstream infections (BSI) caused by bacteria or fungi.Results: During the study period, 1296 positive BC were included: 712 (54.9%) due to Gram-positive (GP), 525 (40.5%) due to Gram-negative (GN) strains, and 59 (4.6%) caused by fungi. Among GN isolates, enterobacteriaceae were reported in 453 (86.3%) cases. PCT values were higher in patients with GN etiology (26.1 +/- 14.2 ng/mL) compared to GP (6.9 +/- 4.5) and fungi (3.3 +/- 2.4). Mean values for CRP in GN, GP, and fungi were not different. Receiver Operating Characteristic (ROC) curves showed an area under curve (AUC) of 0.71 for PCT and 0.51 for CRP among GN isolates; an AUC of 0.7 for PCT and 0.52 for CRP among enterobacteriaceae. Lower AUC for PCT were reported for GP and fungi.Conclusions: PCT showed moderate performance in early detection (within 24 h) of Gram-negative infections, especially those caused by enterobacteriaceae. Further prospective studies are mandatory to confirm these observations. (C) 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences

Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience

Background: Procalcitonin (PCT) is routinely used for an early recognition of severe infections and for promoting appropriate use of antibiotics. However, limited data correlating values of PCT with etiology of infection has been reported.Methods: During 2016, all positive blood cultures (BC) were retrospectively extracted in a 1100-beds Italian tertiary-care hospital. PCT and C-reactive protein (CRP) values were recorded within 24 h from BC collection. Primary endpoint of the study was to investigate the correlation between PCT and CRP values and the occurrence of bloodstream infections (BSI) caused by bacteria or fungi.Results: During the study period, 1296 positive BC were included: 712 (54.9%) due to Gram-positive (GP), 525 (40.5%) due to Gram-negative (GN) strains, and 59 (4.6%) caused by fungi. Among GN isolates, enterobacteriaceae were reported in 453 (86.3%) cases. PCT values were higher in patients with GN etiology (26.1 +/- 14.2 ng/mL) compared to GP (6.9 +/- 4.5) and fungi (3.3 +/- 2.4). Mean values for CRP in GN, GP, and fungi were not different. Receiver Operating Characteristic (ROC) curves showed an area under curve (AUC) of 0.71 for PCT and 0.51 for CRP among GN isolates; an AUC of 0.7 for PCT and 0.52 for CRP among enterobacteriaceae. Lower AUC for PCT were reported for GP and fungi.Conclusions: PCT showed moderate performance in early detection (within 24 h) of Gram-negative infections, especially those caused by enterobacteriaceae. Further prospective studies are mandatory to confirm these observations. (C) 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences

Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience

Background: Procalcitonin (PCT) is routinely used for an early recognition of severe infections and for promoting appropriate use of antibiotics. However, limited data correlating values of PCT with etiology of infection has been reported.Methods: During 2016, all positive blood cultures (BC) were retrospectively extracted in a 1100-beds Italian tertiary-care hospital. PCT and C-reactive protein (CRP) values were recorded within 24 h from BC collection. Primary endpoint of the study was to investigate the correlation between PCT and CRP values and the occurrence of bloodstream infections (BSI) caused by bacteria or fungi.Results: During the study period, 1296 positive BC were included: 712 (54.9%) due to Gram-positive (GP), 525 (40.5%) due to Gram-negative (GN) strains, and 59 (4.6%) caused by fungi. Among GN isolates, enterobacteriaceae were reported in 453 (86.3%) cases. PCT values were higher in patients with GN etiology (26.1 +/- 14.2 ng/mL) compared to GP (6.9 +/- 4.5) and fungi (3.3 +/- 2.4). Mean values for CRP in GN, GP, and fungi were not different. Receiver Operating Characteristic (ROC) curves showed an area under curve (AUC) of 0.71 for PCT and 0.51 for CRP among GN isolates; an AUC of 0.7 for PCT and 0.52 for CRP among enterobacteriaceae. Lower AUC for PCT were reported for GP and fungi.Conclusions: PCT showed moderate performance in early detection (within 24 h) of Gram-negative infections, especially those caused by enterobacteriaceae. Further prospective studies are mandatory to confirm these observations. (C) 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences

Robot-assisted training for upper limb in stroke (ROBOTAS): an observational, multicenter study to identify determinants of efficacy

Background: The loss of arm function is a common and disabling outcome after stroke. Robot-assisted upper limb (UL) training may improve outcomes. The aim of this study was to explore the effect of robot-assisted training using end-effector and exoskeleton robots on UL function following a stroke in real-life clinical practice. Methods: A total of 105 patients affected by a first-ever supratentorial stroke were enrolled in 18 neurorehabilitation centers and treated with electromechanically assisted arm training as an add-on to conventional therapy. Both interventions provided either an exoskeleton or an end-effector device (as per clinical practice) and consisted of 20 sessions (3/5 times per week; 6-8 weeks). Patients were assessed by validated UL scales at baseline (T0), post-treatment (T1), and at three-month follow-up (T2). The primary outcome was the Fugl-Meyer Assessment for the upper extremity (FMA-UE). Results: FMA-UE improved at T1 by 6 points on average in the end-effector group and 11 points on average in the exoskeleton group (p < 0.0001). Exoskeletons were more effective in the subacute phase, whereas the end-effectors were more effective in the chronic phase (p < 0.0001). Conclusions: robot-assisted training might help improve UL function in stroke patients as an add-on treatment in both subacute and chronic stages. Pragmatic and highmethodological studies are needed to confirm the showed effectiveness of the exoskeleton and end-effector devices