A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies.

Association of Group A Exposure and Exacerbations of Chronic Tic Disorders: A Multinational Prospective Cohort Study.

Objective: To examine prospectively the association between group A (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe.

Methods: We followed up 715 children with CTD (age 10.7 ± 2.

Thyroid Hormones Interaction With Immune Response, Inflammation and Non-thyroidal Illness Syndrome.

The interdependence between thyroid hormones (THs), namely, thyroxine and triiodothyronine, and immune system is nowadays well-recognized, although not yet fully explored. Synthesis, conversion to a bioactive form, and release of THs in the circulation are events tightly supervised by the hypothalamic-pituitary-thyroid (HPT) axis. Newly synthesized THs induce leukocyte proliferation, migration, release of cytokines, and antibody production, triggering an immune response against either sterile or microbial insults.

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice.

Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat.

Diabetes and Pancreatic Cancer-A Dangerous Liaison Relying on Carbonyl Stress.

Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity.

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice.

Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat.

BiCoN: network-constrained biclustering of patients and omics data.

Motivation: Unsupervised learning approaches are frequently used to stratify patients into clinically relevant subgroups and to identify biomarkers such as disease-associated genes. However, clustering and biclustering techniques are oblivious to the functional relationship of genes and are thus not ideally suited to pinpoint molecular mechanisms along with patient subgroups.

Results: We developed the network-constrained biclustering approach Biclustering Constrained by Networks (BiCoN) which (i) restricts biclusters to functionally related genes connected in molecular interaction networks and (ii) maximizes the difference in gene expression between two subgroups of patients.

Outcomes of older adults aged 90 and over with cutaneous malignancies after electrochemotherapy with bleomycin: A matched cohort analysis from the InspECT registry.

Background: With extending life expectancy, more people are diagnosed with cutaneous malignancies at advanced ages and are offered nonsurgical treatment. We assessed outcomes of the oldest-old adults after electrochemotherapy (ECT).

Methods: The International Network for Sharing Practices of ECT (InspECT) registry was queried for adults aged ≥90 years (ys) with skin cancers/cutaneous metastases of any histotype who underwent bleomycin-ECT (2006-2019).

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020.

A Major Change in Rate of Climate Niche Envelope Evolution during Hominid History.

is the only species alive able to take advantage of its cognitive abilities to inhabit almost all environments on Earth. Humans are able to culturally construct, rather than biologically inherit, their occupied climatic niche to a degree unparalleled within the animal kingdom. Precisely, when hominins acquired such an ability remains unknown, and scholars disagree on the extent to which our ancestors shared this same ability.

Damage Control Surgery may be a Safe Option for Severe Non-Trauma Peritonitis Management: Proposal of a New Decision-Making Algorithm.

Background: Damage control surgery (DCS) has emerged as a new option in the management of non-traumatic peritonitis patients to increase survival in critically ill patients. The purpose of this study was to compare DCS with conventional strategy (anastomosis/ostomies in the index laparotomy) for severe non-traumatic peritonitis regarding postoperative complications, ostomy rate, and mortality and to propose a useful algorithm in the clinical practice.

Methods: Patients who underwent an urgent laparotomy for non-trauma peritonitis at a single level I trauma center in Colombia between January 2003 and December 2018, were retrospectively included.

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database.

Background: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis.

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

1: ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia.Strong recommendation, high quality evidence.ESGE/ESGAR do not recommend barium enema in this setting.

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

1. ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. Strong recommendation, high quality evidence.

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group.

Intravascular Lithotripsy for Treatment of Calcified Lesions During Carotid Artery Stenting.

Purpose: To report the use of intravascular lithotripsy (IVL) in the treatment of calcified carotid artery lesions.

Materials And Methods: The records of 21 high-surgical-risk patients (mean age 75.1±8.

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

Background: The natural history of facioscapulohumeral muscular dystrophy (FSHD) is undefined.

Methods: An observational cohort study was conducted in 246 FSHD1 patients. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF).

Protocol of an interdisciplinary consensus project aiming to develop an AGREE II extension for guidelines in surgery.

Introduction: Appraisal of Guidelines for Research and Evaluation (AGREE II) is an instrument that informs development, reporting and assessment of clinical practice guidelines. Previous research has demonstrated the need for improvement in methodological and reporting quality of clinical practice guidelines specifically in surgery. We aimed to develop an AGREE II extension document for application in surgical guidelines.

Diabetes promotes invasive pancreatic cancer by increasing systemic and tumour carbonyl stress in Kras mice.

Background: Type 1 and 2 diabetes confer an increased risk of pancreatic cancer (PaC) of similar magnitude, suggesting a common mechanism. The recent finding that PaC incidence increases linearly with increasing fasting glucose levels supports a central role for hyperglycaemia, which is known to cause carbonyl stress and advanced glycation end-product (AGE) accumulation through increased glycolytic activity and non-enzymatic reactions. This study investigated the impact of hyperglycaemia on invasive tumour development and the underlying mechanisms involved.

The Current Clinically Relevant Findings on COVID-19 Pandemic.

The emergence of a novel coronavirus and coronavirus disease 2019 (COVID-19) represents a challenge to global healthcare. In the past 20 years, this is the third coronavirus that jumped the species barrier and infected humans. It is highly contagious but associated with low pathogenicity.

The Deadly Quartet (Covid-19, Old Age, Lung Disease, and Heart Failure) Explains Why Coronavirus-Related Mortality in Northern Italy Was So High.

Since its outbreak in China at the end of 2019, the new coronavirus disease (COVID-19) was characterized by both easy spreading and high mortality. The latter proved to be way more elevated in the North of Italy -with a peak of 18.4% in region Lombardia and even 31% in the city of Bergamo and surrounding county- than in the rest of the world.

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine.