Macrophages treated with interferons induce different responses in lymphocytes via extracellular vesicles.

Limited information exists regarding the impact of interferons (IFNs) on the information carried by extracellular vesicles (EVs). This study aimed at investigating whether IFN-α2b, IFN-ß, IFN-γ, and IFN-λ1/2 modulate the content of EVs released by primary monocyte-derived macrophages (MDM). Small-EVs (sEVs) were purified by size exclusion chromatography from supernatants of MDM treated with IFNs. To characterize the concentration and dimensions of vesicles, nanoparticle tracking analysis was used. SEVs surface markers were examined by flow cytometry. IFN treatments induced a significant down-regulation of the exosomal markers CD9, CD63, and CD81 on sEVs, and a significant modulation of some adhesion molecules, major histocompatibility complexes and pro-coagulant proteins, suggesting IFNs influence biogenesis and shape the immunological asset of sEVs. SEVs released by IFN-stimulated MDM also impact lymphocyte function, showing significant modulation of lymphocyte activation and IL-17 release. Altogether, our results show that sEVs composition and activity are affected by IFN treatment of MDM.

Endovascular aortic arch repair under monitored anaesthesia care: maximizing microinvasiveness.

Patients with aortic arch pathologies after surgery for type-A acute aortic dissection represent a challenging population since open surgery is associated with a non-negligible rate of mortality and complications. Microinvasive endovascular aortic arch repair Arch-Thoracic EndoVascular Aortic Repair (Ar-TEVAR) has shown promising results in high-risk patients. Ar-TEVAR is usually performed under general anaesthesia. We report the case of an 83-year-old man with a history of ascending aorta replacement for type-A acute aortic dissection who was referred for an anastomotic pseudoaneurysm. Ar-TEVAR using an off-the-shelf single-branch aortic arch stent graft was chosen. In order to further minimize procedural invasiveness, monitored anaesthesia care (local anaesthesia with sedation and analgesia) was performed since it provides less stress on the cardiovascular and respiratory systems and overall leads to a faster recovery especially in elderly patients.

Propensity-Weighted Comparison of Conventional Stented and Rapid-Deployment Aortic Bioprostheses.

Aim of this study was to compare early clinical and hemodynamic outcomes of Intuity and ME bioprostheses. A propensity score weighting approach was performed. Preoperative variables were defined according to EuroSCORE criteria and postoperative complications according to VARC-2 definitions. We evaluated 375 patients who underwent SAVR with the 2 study devices. Intuity and ME were implanted in 252 (67.2%) and in 123 (32.8%) patients, respectively. There were no differences in terms of postoperative complications, including mortality (1% in each group; OR 0.46[0.05;4.21]). The incidence of pace-maker implantation was 6% and 5% in Intuity and ME groups, respectively (OR 0.53[0.27;1.07]). Intuity showed significantly lower gradients (Median mean gradients: 9mmHg vs 14mmHg, P<0.001), larger effective orifice area index (1.13cm2/m2 vs 1cm2/m2, P=0.007) and lower incidence of patient-prosthesis mismatch (7.1% vs 22.8%, P=0.006). The RD Intuity provides similar early clinical outcomes but shows significantly better hemodynamic performance compared to the ME valve.

The role of vitamin D in prevention OF COVID-19 and its severity: an umbrella review.

BACKGROUND AND AIM: Vitamin D is known to modulate immune response and its deficiency was associated with respiratory distress in patients hospitalized for pneumonia. Nevertheless, numerous reviews on vitamin D in COVID-19 patients have shown conflicting results, as previously reported also for other respiratory diseases (e.g., influenza). METHODS: This umbrella review aims to assess whether low serum 25-OHD is associated with susceptibility to COVID 19, their severity, and mortality. A total of 1559 studies were excluded after the title, abstract and full-text articles screening and 9 papers were included in this review: 2 systematic reviews and 7 metanalysis. RESULTS: The findings of this review that summarized studies from 5 WHO regions (European Region, Region of the Americas, South-East Asia Region, Eastern Mediterranean Region, Western Pacific Region) to exclusion only African region, show that low serum 25-OHD levels are associated with higher infection risks for COVID-19. CONCLUSIONS: Although the umbrella findings indicate a potential role of vitamin D deficiency in COVID-19 severity in hospitalized patients and showing an association between Vitamin D supplementation and COVID-19 severity, however, more robust data from randomized controlled trials are further needed to confirm a possible association with the mortality rates.

Sociodemographic, clinical and criminological characteristics of a sample of Italian Volterra REMS patients.

BACKGROUND: In Italy the Law 9/2012 prescribed the total closure of forensic psychiatric hospitals (OPGs) and the conversion to a care model based on residential units in the community employing only clinical personnel (Residenze per l'Esecuzione delle Misure di Sicurezza - REMS) and fully integrated in public mental health services. The aim of this study is to report sociodemographic, clinical and criminological characteristics of patients admitted in Volterra REMS since it opened on 01/12/15 up to 31/12/17. METHODS: Sociodemographic and clinical information was collected from official documents (clinical files, ward reports) and from patients' personal health records. Psychiatric diagnoses were made by REMS psychiatrists according to the DSM-5 criteria. Criminological information was obtained from patients' criminal records. RESULTS: Volterra REMS patients' characteristics are similar to those of samples of OPGs patients (unmarried socially disadvantaged males with an average age of 40, no offsprings, low education, high rates of Schizophrenia Spectrum Disorders and medical comorbidity). However, the REMS model presents a very high turnover rate: during the study period 61 patients were admitted while 32 were discharged. Being assisted by public mental health services before committing the crime increased the probability of discharge. In non-EU patients long acting injectable antipsychotics were used more frequently than in community ones. Substance-Related Disorders are the main psychiatric comorbidity and resulted as being more frequent in bipolar patients than in other patients. CONCLUSIONS: Due to the high patients' turnover, we expect a progressive change in sociodemographic, clinical and criminological features of the REMS population. The REMS model provides a return for mentally disordered criminals to the care of local public mental health services which are recovering after many years some of their most challenging patients ensuring their deinstitutionalization and reintegration into society.

Relationship quality of persons with obstructive sleep apnoea syndrome.

In the field of sleep disorders, the quality of couple relationship is arousing increasing attention, given its implications for quality of life and treatment adherence. The aim of the present study was to evaluate relationship quality in a sample of treated or untreated patients with Obstructive Sleep Apnoea Syndrome. Eighty-seven patients were recruited in a hospital-based Centre for Sleep Medicine. Subjects were administered the Dyadic Adjustment Scale (DAS) to evaluate relationship quality, and the Epworth Sleepiness Scale (ESS). Apnoea-hypopnoea indexes (AHI) were collected through nocturnal polysomnography or home testing with a portable monitoring device. Although the DAS average scores were similar to local normative values, relationship quality was significantly lower in the untreated patients when compared with the ones treated. The ESS scores showed a negative correlation with many DAS scores, whereas no significant correlation emerged for AHI. Such data suggest a significant impact of perceived sleep apnoea symptoms on marital satisfaction, even though in the absence of striking differences between the whole sample and the general population.

Recovery of hand function with robot-assisted therapy in acute stroke patients: a randomized-controlled trial.

In the last few years, not many studies on the use of robot-assisted therapy to recover hand function in acute stroke patients have been carried out. This randomized-controlled observer trial is aimed at evaluating the effects of intensive robot-assisted hand therapy compared with intensive occupational therapy in the early recovery phases after stroke with a 3-month follow-up. Twenty acute stroke patients at their first-ever stroke were enrolled and randomized into two groups. The experimental treatment was performed using the Amadeo Robotic System. Control treatment, instead, was carried out using occupational therapy executed by a trained physiotherapist. All participants received 20 sessions of treatment for 4 consecutive weeks (5 days/week). The following clinical scales, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI) and modified Ashworth Scale for wrist and hand muscles (MAS), were performed at baseline (T0), after 20 sessions (end of treatment) (T1) and at the 3-month follow-up (T2). The Barthel Index was assessed only at T0 and T1. Evidence of a significant improvement was shown by the Friedman test for the FM [experimental group (EG): P=0.0039, control group (CG): P<0.0001], Box and Block Test (EG: P=0.0185, CG: P=0.0086), MI (EG: P<0.0001, CG: P=0.0303) and MRC (EG: P<0.0001, CG: P=0.001) scales. These results provide further support to the generalized therapeutic impact of intensive robot-assisted treatment on hand recovery functions in individuals with acute stroke. The robotic rehabilitation treatment may contribute toward the recovery of hand motor function in acute stroke patients. The positive results obtained through the safe and reliable robotic rehabilitation treatment reinforce the recommendation to extend it to a larger clinical practice.

Hand robotics rehabilitation: feasibility and preliminary results of a robotic treatment in patients with hemiparesis.

Background. No strongly clinical evidence about the use of hand robot-assisted therapy in stroke patients was demonstrated. This preliminary observer study was aimed at evaluating the efficacy of intensive robot-assisted therapy in hand function recovery, in the early phase after a stroke onset. Methods. Seven acute ischemic stroke patients at their first-ever stroke were enrolled. Treatment was performed using Amadeo robotic system (Tyromotion GmbH Graz, Austria). Each participant received, in addition to inpatients standard rehabilitative treatment, 20 sessions of robotic treatment for 4 consecutive weeks (5 days/week). Each session lasted for 40 minutes. The exercises were carried out as follows: passive modality (5 minutes), passive/plus modality (5 minutes), assisted therapy (10 minutes), and balloon (10 minutes). The following impairment and functional evaluations, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI), and modified Ashworth Scale for wrist and hand muscles (AS), were performed at the beginning (T0), after 10 sessions (T1), and at the end of the treatment (T2). The strength hand flexion and extension performed by Robot were assessed at T0 and T2. The Barthel Index and COMP (performance and satisfaction subscale) were assessed at T0 and T2. Results. Clinical improvements were found in all patients. No dropouts were recorded during the treatment and all subjects fulfilled the protocol. Evidence of a significant improvement was demonstrated by the Friedman test for the MRC (P < 0.0123). Evidence of an improvement was demonstrated for AS, FM, and MI. Conclusions. This original rehabilitation treatment could contribute to increase the hand motor recovery in acute stroke patients. The simplicity of the treatment, the lack of side effects, and the first positive results in acute stroke patients support the recommendations to extend the clinical trial of this treatment, in association with physiotherapy and/or occupational therapy.

Sorcin induces a drug-resistant phenotype in human colorectal cancer by modulating Ca(2+) homeostasis.

The Ca(2+)-binding protein sorcin regulates intracellular calcium homeostasis and plays a role in the induction of drug resistance in human cancers. Recently, an 18 kDa mitochondrial isoform of sorcin was reported to participate in antiapoptosis in human colorectal cancer (CRC), but information remains lacking about the functional role of the more abundant 22 kDa isoform of sorcin expressed in CRC. We found the 22 kDa isoform to be widely expressed in human CRC cells, whether or not they were drug resistant. Its upregulation in drug-sensitive cells induced resistance to 5-fluorouracil, oxaliplatin, and irinotecan, whereas its downregulation sensitized CRC cells to these chemotherapeutic agents. Sorcin enhances the accumulation of Ca(2+) in the endoplasmic reticulum (ER), preventing ER stress, and, in support of this function, we found that the 22 kDa isoform of sorcin was upregulated under conditions of ER stress. In contrast, RNAi-mediated silencing of sorcin activated caspase-3, caspase-12, and GRP78/BiP, triggering apoptosis through the mitochondrial pathway. Our findings establish that CRC cells overexpress sorcin as an adaptive mechanism to prevent ER stress and escape apoptosis triggered by chemotherapeutic agents, prompting its further investigation as a novel molecular target to overcome MDR.

Novel treatment modalities for Graves' orbitopathy.

Non-surgical treatments for moderate to severe and active Graves' orbitopathy (systemic glucocorticoids with or without orbital radiotherapy) have limited effects on the underlying autoimmune process causing the disease. Although the clinical responses to treatment are often good, at least one third of patients with Graves' orbitopathy are eventually dissatisfied with the treatment outcome. Progress in our understanding of the autoimmune basis of Graves' orbitopathy (although still incomplete) made it possible, similar to other autoimmune disorders, to envision the use of novel immunomodulating drugs. Among the currently available biologic agents, the CD20+ B cell-depleting agent, rituximab, and tumor necrosis factor-alpha inhibitors are presently the drugs that have the best chance of being employed in the future for the treatment of Graves' orbitopathy. However, randomized, controlled clinical trials to support their use are warranted.

Ectopic submandibular thyroid tissue with a coexisting normally located multinodular goitre: case report and review of the literature.

The simultaneous finding of submandibular ectopic thyroid tissue and functional orthotopic thyroid gland is an extremely rare event. The present report describes the case of a woman presenting with a left submandibular mass, distant from a palpable multinodular goitre. Ultrasonography showed an ovoidal solid mass adjacent to the lower margin of the left submandibular gland. Cytological specimens showed colloid material and thyroid follicular cells with no malignant features. A preoperative CT scan demonstrated a very thin connection between the thyroid and the submandibular mass. The patient underwent total thyroidectomy and excision of the submandibular mass. The histopathological diagnosis of the thyroid tissue was multinodular goitre, and the submandibular mass was ectopic thyroid tissue showing a hyperplastic pattern. The main differential diagnosis of the submandibular mass was a metastasis from a well differentiated cancer. This case illustrates that an ectopic thyroid off the midline may not necessarily be a metastasis from a thyroid cancer.

Nevirapine toxicity in non-HIV cancer patients.

BACKGROUND: Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor used in HIV patients and recently evaluated as a differentiating and antiproliferative agent in human malignancies. However, while NVP is a safe treatment in immunocompromised patients, NVP-containing regimens have been associated with severe immune-mediated toxicities in non-HIV individuals. METHODS AND RESULTS: We describe the toxicity profile of single-agent NVP in 6 non-HIV cancer patients treated for a median period of 7.3 months (range 1-24), reporting only a reversible grade III increase in glutamyl transpeptidase and glutamic pyruvic transaminase serum values. Interestingly, NVP treatment correlates with either a decrease in CD8+ T cell counts or a parallel increase in CD4/CD8 ratio, antithyroglobulin and antithyroid peroxidase autoantibody titers. CONCLUSIONS: These results, although obtained in a small cohort of patients, suggest that the toxicity profile of single-agent NVP may be worth testing in a phase I/II study in non-HIV cancer patients and that NVP toxicity may depend on its capacity to trigger autoimmune responses in susceptible individuals.

Comorbidity with axis I anxiety disorders in remitted psychotic patients 1 year after hospitalization.

INTRODUCTION: Comorbid anxiety disorders are frequently encountered in psychoses and mainly assessed during the hospitalization. METHODS: Comorbidity was investigated in 98 patients with schizophrenia, schizoaffective, or bipolar disorder, previously hospitalized for psychotic symptoms. Assessments, including Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Brief Psychiatric Rating Scale, and Clinical Global Impressions Scale, were performed during hospitalization (t0) and subsequently in a phase of remission (t1). Comorbidity was assessed at t1 only. RESULTS: One or more comorbid anxiety diagnoses were made in 46 (46.9%) patients. Of these, 15 (32.6%) received multiple anxiety diagnoses, while 31 (67.4%) single anxiety diagnoses. Schizophrenic patients had a rate of social anxiety disorder (SAD) higher (P<.05) than the others. Patients assessed with panic disorder or with obsessive-compulsive disorder at t1 showed significantly greater severity of illness at t0; patients with SAD demonstrated greater severity at t1. No significant differences in the rates of individual anxiety disorders were found in patients treated with typical or atypical antipsychotics or with both. CONCLUSION: Anxiety disorders, particularly obsessive-compulsive disorder, panic disorder and SAD, seem to be frequently comorbid in remitted psychotic patients; SAD would be more prevalent in schizophrenia and might negatively impact the course of the illness.