Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model

Cardiovascular Drugs and Therapy - Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated...     

COVID-19 as a trigger of irritable bowel syndrome: A review of potential mechanisms

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.     

Combined hepatic and portal vein embolization as preparation for major hepatectomy: a systematic review

BackgroundSome patients remain deemed unsuitable for resection after portal vein embolization (PVE) because of insufficient hypertrophy of the future remnant liver (FRL). Hepatic and portal vein embolization (HPVE) has been shown to induce hypertrophy of the FRL. The aim of this study was to provide a systematic review of the available literature on HPVE as preparation for major hepatectomy.MethodsThe literature search was performed on online databases. Studies including patients who underwent preoperative HPVE were retrieved for evaluation.ResultsSix articles including 68 patients were published between 2003 and 2017. HPVE was performed successfully in all patients with no mortality and morbidity-related procedures. The degree of hypertrophy of the FRL after HPVE ranged from 33% to 63.3%. Surgical resection after preoperative HPVE could be performed in 85.3% of patients, but 14.7% remained unsuitable for resection because of insufficient hypertrophy of the FRL or tumor progression. Posthepatectomy morbidity and mortality rates were 10.3% and 5.1%, respectively. The postoperative liver failure rate was nil.ConclusionHPVE as a preparation for major hepatectomy appears to be feasible and safe and could increase the resectability of patients initially deemed unsuitable for resection because of absent or insufficient hypertrophy of the FRL after PVE alone.     

Neural plasticity and adult neurogenesis: the deep biology perspective

The recognition that neurogenesis does not stop with adolescence has spun off research towards the reduction of brain disorders by enhancing brain regeneration. Adult neurogenesis is one of the tougher problems of developmental biology as it requires the generation of complex intracellular and pericellular anatomies, amidst the danger of neuroinflammation. We here review how a multitude of regulatory pathways optimized for early neurogenesis has to be revamped into a new choreography of time dependencies. Distinct pathways need to be regulated, ranging from neural growth factor induced differentiation to mitochondrial bioenergetics, reactive oxygen metabolism, and apoptosis. Requiring much Gibbs energy consumption, brain depends on aerobic energy metabolism, hence on mitochondrial activity. Mitochondrial fission and fusion, movement and perhaps even mitoptosis, thereby come into play. All these network processes are interlinked and involve a plethora of molecules. We recommend a deep thinking approach to adult neurobiology.     

New drugs in early-stage clinical trials for allergic rhinitis

Introduction: Allergic rhinitis (AR) is the most common allergic disease, and it has a relevant impact on the quality of life of the patient. Treatment of AR includes a combination of strategies of proven efficacy and effectiveness; however, a relevant proportion of patients remain uncontrolled.

Areas covered: This review article summarizes emerging therapeutic approaches to AR; these approaches include nasal sprays, oral drugs, alternative allergen immunotherapy administration routes, and biologic agents.

Expert opinion: The agents discussed require further clinical trials to prove their efficacy in the treatment of AR. Some of these agents, in particular, allergen immunotherapies and biologics, have the potential to form crucial precision medicine approaches to AR. Those that prove their efficacy in clinical trials must also be evaluated from a pharmacoeconomic perspective, possibly in real-life studies; this will define which therapeutic strategies achieve the most convenient and cost-effective ratio, thus yielding a novel opportunity for the most severe and previously treatment-resistant allergic patients.     

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.