The emerging role of immunotherapy in biliary tract cancer: a review of new evidence and predictive biomarkers.

Biliary tract cancers (BTCs) are frequently diagnosed in advanced stages and are highly lethal. Immunotherapy may play a role in the treatment of these patients. Promising results come from monotherapy or combination therapy studies in pretreated patients.

Effect of Myosin Isoforms on Cardiac Muscle Twitch of Mice, Rats and Humans.

To understand how pathology-induced changes in contractile protein isoforms modulate cardiac muscle function, it is necessary to quantify the temporal-mechanical properties of contractions that occur under various conditions. Pathological responses are much easier to study in animal model systems than in humans, but extrapolation between species presents numerous challenges. Employing computational approaches can help elucidate relationships that are difficult to test experimentally by translating the observations from rats and mice, as model organisms, to the human heart.

The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring.

Objective: Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF.

Methods: The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF.

Robot-assisted surgery in space: pros and cons. A review from the surgeon's point of view.

The target of human flight in space has changed from permanence on the International Space Station to missions beyond low earth orbit and the Lunar Gateway for deep space exploration and Missions to Mars. Several conditions affecting space missions had to be considered: for example the effect of weightlessness and radiations on the human body, behavioral health decrements or communication latency, and consumable resupply. Telemedicine and telerobotic applications, robot-assisted surgery with some hints on experimental surgical procedures carried out in previous missions, had to be considered as well.

Prevalence of nutritional risk and malnutrition during and after hospitalization for COVID-19 infection: Preliminary results of a single-centre experience.

Background & Aims: The effect of the COVID-19 infection on nutritional status is not well established. Worldwide epidemiological studies have begun to investigate the incidence of malnutrition during hospitalization for COVID-19. The prevalence of malnutrition during follow-up after COVID-19 infection has not been investigated yet.

The New Challenge in the Management of Proximal Femur Fractures during SARS Cov-2 outbreak.

The aim of this study is to evaluate how the spread of Sars-Cov-2 has changed the epidemiology of proximal femur fractures in two major trauma centers in Italy, understanding the workload and the best allocation of the resources for the orthopedics department in such an emergency situation. The rate of patients from January 2019 to April 2020 hospitalized with femoral neck fractures (group A) and trochanteric fractures (group B) were recorded. Demographic data, timing of surgical treatment and the length of stay were recorded.

Clinical and Laboratory Follow-up After Hospitalization for COVID-19 at an Italian Tertiary Care Center.

We evaluated 100 postacute coronavirus disease 2019 (COVID-19) patients a median (interquartile range) of 60 (48-67) days after discharge from the Careggi University Hospital, Italy. Eighty-four (84%) had at least 1 persistent symptom, irrespective of COVID-19 severity. A considerable number of hospital readmissions (10%) and/or infectious diseases (14%) during the postdischarge period were reported.

Human Recombinant Relaxin (Serelaxin) as Anti-fibrotic Agent: Pharmacology, Limitations and Actual Perspectives.

Relaxin (recombinant human relaxin-2 hormone; RLX-2; serelaxin) had raised expectations as a new medication for fibrotic diseases. A plethora of in vitro and in vivo studies have offered convincing demonstrations that relaxin promotes remodeling of connective tissue extracellular matrix mediated by inhibition of multiple fibrogenic pathways, especially the downstream signaling of transforming growth factor (TGF)-β1, a major pro-fibrotic cytokine, and the recruitment and activation of myofibroblasts, the main fibrosis-generating cells. However, all clinical trials with relaxin in patients with fibrotic diseases gave inconclusive results.

The effect of variable troponin C mutation thin filament incorporation on cardiac muscle twitch contractions.

One of the complexities of understanding the pathology of familial forms of cardiac diseases is the level of mutation incorporation in sarcomeres. Computational models of the sarcomere that are spatially explicit offer an approach to study aspects of mutational incorporation into myofilaments that are more challenging to get at experimentally. We studied two well characterized mutations of cardiac TnC, L48Q and I61Q, that decrease or increase the release rate of Ca from cTnC, k, resulting in HCM and DCM respectively [1].

Novel biomarkers in cardiovascular surgery.

Cardiovascular disease includes health problems related to the heart, arteries and veins and is a significant healthcare problem worldwide. Cardiovascular disease may be acute or chronic and relapses are frequent. Biomarkers involved in this field may help clinicians and surgeons in diagnosis and adequate decision making.

Multiscale modeling of twitch contractions in cardiac trabeculae.

Understanding the dynamics of a cardiac muscle twitch contraction is complex because it requires a detailed understanding of the kinetic processes of the Ca2+ transient, thin-filament activation, and the myosin-actin cross-bridge chemomechanical cycle. Each of these steps has been well defined individually, but understanding how all three of the processes operate in combination is a far more complex problem. Computational modeling has the potential to provide detailed insight into each of these processes, how the dynamics of each process affect the complexity of contractile behavior, and how perturbations such as mutations in sarcomere proteins affect the complex interactions of all of these processes.

Adiponectin Exerts Peripheral Inhibitory Effects on the Mouse Gastric Smooth Muscle through the AMPK Pathway.

Some adipokines, such as adiponectin (ADPN), other than being implicated in the central regulation of feeding behavior, may influence gastric motor responses, which are a source of peripheral signals that also influence food intake. The present study aims to elucidate the signaling pathways through which ADPN exerts its actions in the mouse gastric fundus. To this purpose, we used a multidisciplinary approach.

Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria.

In the last decades, there was an important paucity of agents for adequately treating infections due to metallo-β-lactamases-producing Gram-negative bacteria (MBL-GNB). Cefiderocol, a novel siderophore cephalosporin showing activity against MBL-GNB, has been recently marketed, and a combination of aztreonam and ceftazidime/avibactam has shown a possible favorable effect on survival of patients with severe MBL-GNB infections in observational studies. Other agents showing activity against MBL-GNB are currently in clinical development (e.

Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study.

Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioid receptors commonly used to treat opioid addiction; its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects.

Evolution and new frontiers of histology in bio-medical research.

Histology refers to the study of the morphology of cells within their natural tissue environment. As a bio-medical discipline, it dates back to the development of first microscopes which allowed to override the physical visual limitation of the human eye. Since the first observations, it was understood that cell shape predicts function and, therefore, shape alterations can identify and explain dysfunction and diseases.

Spatial and Functional Distribution of Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Pathogenic variants in , encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique variants and relatively small genotyped hypertrophic cardiomyopathy cohorts have precluded detailed genotype-phenotype correlations.

Methods: Patients with hypertrophic cardiomyopathy and variants were identified from the Sarcomeric Human Cardiomyopathy Registry.

Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia-Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation.

Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis.

Melanoma brain metastases: review of histopathological features and immune-molecular aspects.

Patients with melanoma brain metastases (MBM) have a dismal prognosis, but the unprecedented advances in systemic therapy alone or in combination with local therapy have now extended the 1-year overall survival rate from 20-25% to nearing 80-85%, mainly in asymptomatic patients. The histopathological and molecular characterization of MBM and the understanding of the microenvironment are critical to more effectively manage patients with advanced melanoma and to design biologically driven clinical trials. This review aims to give an overview of the main histopathological features and the immune-molecular aspects of MBM.

Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study.

Introduction: Delta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation.

Materials And Methods: This prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline.

Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions.

The management of chronic visceral pain related to Inflammatory Bowel Diseases or Irritable Bowel Syndrome is still a clinical problem and new therapeutic strategies continue to be investigated. In the present study, the efficacy of a pomegranate decoction and of its polysaccharide and ellagitannin components in preventing the development of colitis-induced abdominal pain in rats was evaluated. After colitis induction by 2,4-dinitrobenzenesulfonic acid (DNBS), the pomegranate decoction (300 mg kg), polysaccharides (300 mg kg), and ellagitannins (45 mg kg) were orally administered for 14 days.

Recombinant human H2 relaxin (serelaxin) as a cardiovascular drug: aiming at the right target.

Serelaxin (recombinant human relaxin-2 hormone; RLX-2) had raised expectations as a new medication for cardiovascular diseases. Evidence from preclinical studies indicated that serelaxin has chronotropic, inotropic, and anti-arrhythmic actions on the myocardium and cardioprotective effects mediated by vasodilation, angiogenesis, and inhibition of inflammation and fibrosis. However, clinical trials with serelaxin in patients with acute heart failure (AHF) gave inconclusive results.

Histamine H Receptors Expressed in Ventral Horns Modulate Spinal Motor Output.

Motoneuron activity is modulated by histamine receptors. While H and H receptors have been widely explored, H histamine receptors (HRs) have not been sufficiently characterized. This paper targets the effects of the selective activation of HRs and their expression on the membranes of large ventral horn cells.