Cardiovascular risk factors and metabolic syndrome in patients treated with long-acting injectables antipsychotics: a retrospective study.

The present cross-sectional, retrospective study aimed to assess the prevalence of cardiovascular disease (CVD) risk factors and metabolic syndrome in a sample of psychiatric patients treated with long-acting injectable antipsychotics (LAIs). The clinical charts of 120 patients, mainly diagnosed with schizophrenia (30.0%), schizoaffective disorder (15.0%), and bipolar disorder (13.3%) on LAIs therapy - initiated in the period from 2013 to 2019 and lasting at least one year - were retrospectively reviewed and related socio-demographic, clinical and laboratory variables were collected. The 70.8% of patients were treated with first-generation LAIs, and the remaining 29.2% with second-generation LAIs. The overall sample showed low compliance in performing the required exams and evaluations related to CVD risk factors. The prevalence of metabolic syndrome was 30.8%, and, considering specific CVD risk factors, 55% of the total sample reported abdominal obesity, 43.3% arterial hypertension, 41.7% low HDL-cholesterol, 25.8% hypertriglyceridemia, and 20.8% fasting hyperglycemia. Lastly, 6.7% showed prolonged corrected QT (QTc) interval at the ECG. Patients treated with LAIs should be regularly monitored for metabolic changes and CVD risk factors. Metabolic changes rapidly develop after initiating an antipsychotic therapy and these often involve parameters, that can be easily recorded in an outpatient setting (e.g. abdominal obesity and hypertension).

Ceftazidime-Avibactam for the Treatment of Multidrug-Resistant Pathogens: A Retrospective, Single Center Study.

Background: Ceftazidime/avibactam is a new cephalosporin/beta-lactamase inhibitor combination approved in 2015 by the FDA for the treatment of complicated intra-abdominal and urinary tract infection, hospital-acquired pneumoniae and Gram-negative infections with limited treatment options. Methods: In this retrospective study, we evaluate the efficacy of ceftazidime/avibactam treatment in 81 patients with Gram-negative infection treated in our center from January 2018 to December 2019. The outcome evaluated was 30-days survival or relapse of infection after the first positive blood culture. Results: the majority of patients were 56 male (69%), with median age of 67. Charlson's Comorbidity Index was >3 in 58 patients. In total, 46% of the patients were admitted into the medical unit, 41% in the ICU, and 14% in the surgical ward. Of the patients, 78% had nosocomial infections, and 22% had healthcare-related infections. The clinical failure rate was 35%: 13 patients died within 30 days from the onset of infection. The outcome was influenced by the clinical condition of the patients: solid organ transplantation (p = 0.003) emerged as an independent predictor of mortality; non-survival patients most frequently had pneumonia (p = 0.009) or mechanical ventilation (p = 0.049). Conclusion: Ceftazidime−avibactam showed high efficacy in infections caused by MDR Gram-negative pathogens with limited therapeutic options.

Use of Dalbavancin in Skin, Bone and Joint Infections: A Real-Life Experience in an Italian Center.

Dalbavancin is a lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). The aim of the study was to evaluate the efficacy and safety in all patients who received at least one administration of dalbavancin. METHODS: We carried out a retrospective study of the use of dalbavancin in 55 patients at the Azienda Ospedaliera Ospedali Riuniti Umberto I (Ancona, Italy) from February 2017 to May 2020 and compared "on label" and "off label" use of dalbavancin in ABSSSI and non-ABSSSI. RESULTS: A total of 55 patients were included in the study. The median age was 61 years; 51% had ABSSSI; 24% had prosthetic joint infections, and 14% had osteomyelitis. A total of 53% received a single 1500 mg infusion of dalbavancin, and 18% received a second dose 14 days later; 24% of patients received further doses at 14-day intervals. In 91% of cases, patients achieved clinical objectives with dalbavancin: 96% of patients with ABSSSI and 69% of those with prosthetic joint infections. CONCLUSIONS: Dalbavancin was shown to have an excellent tolerability profile and to be a highly successful therapeutic approach even in those cases treated "off-label".

Pleiotropic effects of hexavalent chromium (CrVI) in Mytilus galloprovincialis digestive gland.

Hexavalent Chromium Cr(VI) is an important contaminant considered as a model oxidative toxicant released from both domestic and industrial effluents, and represents the predominant chemical form of the metal in aquatic ecosystems. On the other hand, in mammals the reduced form Cr(III) is considered an essential microelement, involved in regulation of lipid and carbohydrate metabolism; moreover, recent evidence suggests that Cr may have endocrine effects. In this work, the effects of Cr(VI) were investigated in the digestive gland of the marine bivalve Mytilus galloprovincialis. Mussels were exposed to 0.1-1-10-100 µg Cr(VI) L(-1) animal(-1) for 96 h. At 100 µg L(-1), a large increase in total Cr tissue content was observed; in these conditions, the lysosomal membranes were completely destabilized, whereas other lysosomal biomarkers (neutral lipids-NL and lipofuscin-LF), as well as different enzyme activities and gene expression were unaffected, this indicating severe stress conditions in the tissue. On the other hand, at lower concentrations, changes in other histochemical, biochemical and molecular endpoints were observed. In particular, at both 1 and 10 µg L(-1), lysosomal destabilization was associated with significant NL and LF accumulation; however, no changes in catalase and GSH transferase (GST) activities were observed. At the same concentrations, GSSG reductase (GSR) activity was significantly increased, this probably reflecting the recycling of GSSG produced in the GSH-mediated intracellular reduction of Cr(VI). Increased activities of the key glycolytic enzymes PFK (phosphofructokinase) and PK (pyruvate kinase) were also observed, indicating that Cr(VI) could affect carbohydrate metabolism. Cr(VI) induced downregulation or no effects on the expression of metallothioneins MT10 and MT20, except for an increase in MT20 transcription in males. Moreover, significant up-regulation of the Mytilus estrogen receptor MeER2 and serotonin receptor (5-HTR) were observed in both sexes. The results demonstrate that exposure to Cr(VI) in the low ppb range did not result in strong toxicity or oxidative stress conditions in mussel digestive gland. On the other hand, our data support the hypothesis that low concentrations of the metal can exert pleiotropic effects on mussel physiology, from modulation of lipid and carbohydrate metabolism, to effects on the expression of estrogen-responsive genes.

Increased apoptosis in circulating lymphocyte cultures of anti-RNA polymerase III positive patients with systemic sclerosis.

The sera of 39 patients (38 women and 1 man), 16 with limited and 23 with diffuse clinical form of systemic sclerosis (SSc), were tested for anti-centromere (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (ARA) antibodies. The presence of apoptotic cells in cultures of circulating lymphocytes was investigated using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) technique. ACAs were present in 16 (41%), ATA in 15 (38%) and ARA in 8 (21%) cases. The mean frequency of apoptotic lymphocytes was statistically higher in the ARA positive patients with respect to that in the control population (P < 0.001), in ACA (P < 0.001) and in the ATA (P < 0.001) groups. Moreover, apoptosis was distributed homogenously in ACA and ATA positive subjects, but not in the ARA patients. Our results show that there is an increase in apoptosis in the lymphocytes of ARA positive SSc patients.

Unstabilized DNA breaks in lymphocytes of patients with different subsets of systemic sclerosis.

The clastogenic effects on DNA, proven by the presence of micronuclei (MN) and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in three subsets of patients with systemic sclerosis (SSc). The frequency of MN found in cultures of peripheral lymphocytes in patients with anticentromere and antitopoisomerase I antibodies was significantly higher than that in the control group. The group with anticentromere antibody showed a significantly higher frequency of MN than did the subjects with antitopoisomerase antibody (4.22% versus 2.34%, P < 0.001). Patients with anti-RNA polymerase III, instead, had a low prevalence of typical micronucleated cells (0.98%), not significantly different from that of the healthy controls (0.82%). Moreover, when MN was characterized for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase, its frequency was found to be increased in the groups with anticentromere and antitopoisomerase I antibodies with respect to that in the controls. The increase was significantly higher in the lymphocytes of the patients with anticentromere than in those with antitopoisomerase I antibody (35% versus 20.08%, P < 0.001). Nonetheless, the prevalence of unstable DNA fragments in patients with anti-RNA polymerase III antibody was low (2.05%) and not significantly different from that of the control group (1.18%). Our results indicate that there is a clastogenic effect on DNA and an interference in the protective cellular mechanisms normally stabilizing DNA breaks only in some subsets of SSc patients.