Patients with pre-existing cardiovascular disease (CVD) might be more susceptible to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have higher mortality rates. Nevertheless, the risk of mortality has not been previously quantified. The aim of this meta-analysis is to quantify the risk of mortality in coronavirus disease 2019 (COVID-19) patients. A meta-analysis was conducted analyzing the impact of (1) sex, (2) age, (3) CVD with coronary artery disease (CAD), (4) CAD alone, (5) CVD without CAD, (6) hypertension, (7) cerebrovascular diseases, and (8) diabetes on mortality. Relative risk was assessed for dichotomous variables, mean difference for continuous variables. Twenty-six studies were included, encompassing 8497 patients. Males had 16% higher risk of mortality than females (p < 0.05) and elderly patients had higher chance of dying than younger patients (p < 0.0001). Patients with overall CVD have a 1.96-fold higher mortality risk (p < 0.0001). CAD increases risk of mortality by 1.90-fold (p < 0.05). CVD-CAD were found to increase risk up to 2.03-fold (p < 0.05). Hypertension, cerebrovascular disease and diabetes increase the risk of death up to 1.73-fold, 1.76-fold and 1.59-fold, respectively (p < 0.0001, p < 0.0001, p < 0.05, respectively). Sex, age, presence of CAD and/or other types of CVD, hypertension, cerebrovascular diseases and diabetes mellitus increase mortality in patients with COVID-19. Full article

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m²; albuminuria and eGFR <60 mL/min/1.73 m². Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines. Full article

Survivorship care that is shared between oncology and primary care providers may be a suitable model to effectively and efficiently care for the growing survivor population, however recommendations supporting implementation are lacking. This qualitative study aimed to explore health care professionals’ (HCPs) perceived facilitators and barriers to the implementation, delivery and sustainability of shared survivorship care. Data were collected via semi-structured focus groups and analysed by inductive thematic analysis. Results identified four overarching themes: (1) considerations for HCPs; (2) considerations regarding patients; (3) considerations for planning and process; and (4) policy implications. For HCPs, subthemes included general practitioner (GP, primary care physician) knowledge and need for further training, having clear protocols for follow-up, and direct communication channels between providers. Patient considerations included identifying patients suitable for shared care, discussing shared care with patients early in their cancer journey, and patients’ relationships with their GPs. Regarding process, subthemes included rapid referral pathways back to hospital, care coordination, and ongoing data collection to inform refinement of a dynamic model. Finally, policy implications included development of policy to support a consistent shared care model, and reliable and sustainable funding mechanisms. Based on study findings, a set of recommendations for practice and policy were developed. Full article

Modest weight loss enhances clinical control over cardiovascular disease (CVD) risk factors in overweight and obese individuals. This study aimed to assess the associations between individual weight loss and predefined criteria for clinical improvement in blood pressure, lipid levels, and glycemia. A two-year follow-up study involved 3388 (37.9% men) aged 45−64 years, BMI ≥ 25 kg/m². Changes in body weight were calculated as a percentage of baseline weight; outcome variables: systolic (SBP), diastolic (DBP) blood pressure, high-density (HDL-C) and low-density (LDL-C) lipoproteins, fasting blood glucose (FBG), and triglycerides (TG) were construed as the differences between baseline and outcome values. Clinically significant improvement was defined as SBP/DBP reduction by 5 mm/Hg, FBG−20 mg/dL, LDL-C-10 mg/dL, TG−40 mg/dL, and HDL-C increase by 5 mg/dL. Apart from LDL-C, a modest 5%–10% weight loss was associated with clinically significantly improved outcomes. The incident rate ratios and 95% confidence intervals for clinical improvement of SBP were: 1.27 (1.14–1.40), DBP/1.30 (1.12–1.50), HDL/1.54 (1.18–2.02), and TG/1.69 (1.32–2.17). In the higher category of weight loss, associations were still manifest, although the results proved diagnostically challenging (low number of cases). Even though modest weight loss does enhance clinical control over CVD risk factors, offering regular medical guidance to patients is postulated to further boos the anticipated outcomes. Full article

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention. Full article

To assess neck disability with respect to jaw disability, craniocervical position, cervical alignment, and sensorimotor impairments in patients with temporomandibular disorders (TMD), a systematic review and meta-analysis of observational studies trials were conducted. The meta-analysis showed statistically significant differences in the association between neck disability and jaw disability (standardized mean difference (SMD), 0.72 (0.56–0.82)). However, results showed no significant differences for cervical alignment (SMD, 0.02 (−0.31–0.36)) or for the craniocervical position (SMD, −0.09 (−0.27–0.09)). There was moderate evidence for lower pressure pain thresholds (PPT) and for limited cervical range of motion (ROM). There was limited evidence for equal values for maximal strength between the patients with TMD and controls. There was also limited evidence for reduced cervical endurance and conflicting evidence for abnormal electromyographic (EMG) activity and motor control in TMD patients. Results showed a clinically relevant association between cervical and mandibular disability in patients with TMD. Regarding sensory-motor alterations, the most conclusive findings were observed in the reduction of PPT and cervical ROM, with moderate evidence of their presence in the patients with TMD. Lastly, the evidence on impaired motor control and cervical EMG activity in patients with TMD was conflicting. Full article

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presence of a combined phenotype—defined as both pulmonary AVMs and brain VMs—was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype (p < 0.001). We conclude that genotype–phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype. Full article

Excoriation disorder is a psychocutaneous disorder characterized by repetitive skin-picking and associated with significant morbidity. Currently, epidemiological data in patients with excoriation disorder are lacking so we sought to characterize common patient demographics and comorbidities. We conducted a retrospective case-control study comparing 250 patients with excoriation disorder with 250 age-, race- and sex-matched controls identified between 2007 and 2019 at a single tertiary care center. We found that the majority of excoriation disorder patients were female (76%), Caucasian (82%) and unmarried (62%), with a mean age of 49 years. Compared to the matched controls, patients with excoriation disorder had increased odds of several psychiatric illnesses, including obsessive compulsive disorder (odds ratio (OR) 28.48, 95% confidence interval (CI): 1.68, 481.75), substance use disorder (OR 24.33, 95% CI: 5.81, 101.77), post-traumatic stress disorder (OR 8.23, 95% CI: 2.24, 129.40), depression (OR 8.19, 95% CI: 4.86, 13.80), bipolar disorder (OR 7.55, 95% CI: 2.22, 25.65), attention-deficit/hyperactivity disorder (OR 5.63, 95% CI: 1.62, 19.57), and anxiety (OR 5.01, 95% CI: 2.92, 8.62). Only a minority (42%) of patients were given psychiatry referrals and of those referred, a majority (64%) did not follow-up with psychiatry. The outcomes were also generally unfavorable as only 21% of patients experienced a resolution or improvement in their symptoms. This highlights the need for a multidisciplinary approach to manage patients with excoriation disorder, involving both dermatologists and psychiatrists. Full article

Cardiac mechanical energetic efficiency is the ratio of external work (EW) to the total energy consumption. EW performed by the left ventricle (LV) during a single beat is represented by LV stroke work and may be calculated from the pressure–volume loop area (PVLA), while energy consumption corresponds to myocardial oxygen consumption (MVO₂) expressed on a per-beat basis. Classical early human studies estimated total mechanical LV efficiency at 20–30%, whereas the remaining energy is dissipated as heat. Total mechanical efficiency is a joint effect of the efficiency of energy transfer at three sequential stages. The first step, from MVO₂ to adenosine triphosphate (ATP), reflects the yield of oxidative phosphorylation (i.e., phosphate-to-oxygen ratio). The second step, from ATP split to pressure–volume area, represents the proportion of the energy liberated during ATP hydrolysis which is converted to total mechanical energy. Total mechanical energy generated per beat—represented by pressure–volume area—consists of EW (corresponding to PVLA) and potential energy, which is needed to develop tension during isovolumic contraction. The efficiency of the third step of energy transfer, i.e., from pressure–volume area to EW, decreases with depressed LV contractility, increased afterload, more concentric LV geometry with diastolic dysfunction and lower LV preload reserve. As practical assessment of LV efficiency poses methodological problems, De Simone et al. proposed a simple surrogate measure of myocardial efficiency, i.e., mechano-energetic efficiency index (MEEi) calculated from LV stroke volume, heart rate and LV mass. In two independent cohorts, including a large group of hypertensive subjects and a population-based cohort (both free of prevalent cardiovascular disease and with preserved ejection fraction), low MEEi independently predicted composite adverse cardiovascular events and incident heart failure. It was hypothesized that the prognostic ability of low MEEi can result from its association with both metabolic and hemodynamic alterations, i.e., metabolic syndrome components, the degree of insulin resistance, concentric LV geometry, LV diastolic and discrete systolic dysfunction. On the one part, an increased reliance of cardiomyocytes on the oxidation of free fatty acids, typical for insulin-resistant states, is associated with both a lower yield of ATP per oxygen molecule and lesser availability of ATP for contraction, which might decrease energetic efficiency of the first and second step of energy transfer from MVO₂ to EW. On the other part, concentric LV remodeling and LV dysfunction despite preserved ejection fraction can impair the efficiency of the third energy transfer step. In conclusion, the association of low MEEi with adverse cardiovascular outcome might be related to a multi-step impairment of energy transfer from MVO₂ to EW in various clinical settings, including metabolic syndrome, diabetes, hypertension and heart failure. Irrespective of theoretical considerations, MEEi appears an attractive simple tool which couldt improve risk stratification in hypertensive and diabetic patients for primary prevention purposes. Further clinical studies are warranted to estimate the predictive ability of MEEi and its post-treatment changes, especially in patients on novel antidiabetic drugs and subjects with common metabolic diseases and concomitant chronic coronary syndromes, in whom the potential relevance of MEE can be potentiated by myocardial ischemia. Full article

Background: Limited available evidence suggests that a small proportion of inpatients undergo prolonged hospitalization and use a disproportionate number of bed days. Understanding the factors contributing to prolonged hospitalization may improve patient care and reduce the length of stay in such patients. Methods: We undertook a retrospective cohort study of adult (≥20 years) patients admitted for at least 24 h between 14 November 2016 and 14 November 2018 to hospitals in Victoria, Australia. Data including baseline demographics, admitting specialty, survival status and discharge disposition were obtained from the Victorian Admission Episode Dataset. Multivariable logistic regression analysis was used to identify factors independently associated with prolonged hospitalization (≥14 days). Cox proportional hazard regression model was used to examine the association between various factors and in-hospital mortality. Results: There were almost 5 million hospital admissions over two years. After exclusions, 1,696,112 admissions lasting at least 24 h were included. Admissions with prolonged hospitalization comprised only 9.7% of admissions but utilized 44.2% of all hospital bed days. Factors independently associated with prolonged hospitalization included age, female gender, not being in a relationship, being a current smoker, level of co-morbidity, admission from another hospital, admission on the weekend, and the number of admissions in the prior 12 months. The in-hospital mortality rate was 5.0% for those with prolonged hospitalization compared with 1.8% in those without (p < 0.001). Prolonged hospitalization was also independently associated with a decreased likelihood of being discharged to home (OR 0.53, 95% CI 0.52–0.54). Conclusions: Patients experiencing prolonged hospitalization utilize a disproportionate proportion of bed days and are at higher risk of in-hospital death and discharge to destinations other than home. Further studies are required to identify modifiable factors contributing to prolonged hospitalization as well as the quality of end-of-life care in such admissions. Full article

B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily, is universally expressed by normal and neoplastic plasma cells and plays a critical role in the proliferation, survival and tumor progression in multiple myeloma (MM). B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have been recognized as proliferation ligands for BCMA in the bone marrow microenvironment. Soluble BCMA levels in the serum correlates with disease phase and tumor burden and is a predictor of progression-free survival (PFS) and overall survival (OS). Recently, the introduction of new monoclonal antibodies against CD38 (Daratumumab and Isatuximab) and SLAM7 (Elotuzumab) has changed the therapeutic approach to MM, improving the response rate and the time to progression, both in newly diagnosed and refractory/relapsed patients. Among the surface antigens on MM cells, BCMA is a suitable target for the design of new antibody-based strategies. Experimental approaches targeting BCMA are currently being investigated and include antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs) and genetically engineered T-cells with chimeric antigen receptors (CAR). In this review we summarize the more recent findings about BCMA biologic rationale as a therapeutic target and report the updated results of preclinical and clinical studies focused on ADCs and bsAbs targeting BCMA. Full article

Backgrounds: The etiology of gastroesophageal reflux disease (GERD) including reflux esophagitis and non-erosive reflux disease is multifactorial and a recent meta-analysis showed no association between the development of GERD and Helicobacter pylori eradication in both Western and East-Asian populations. However, the problem remains that various inclusion criteria are used in these studies, which hinders meta-analysis. With a focus on reflux esophagitis with endoscopic mucosal injury, we meta-analysed to evaluate the association between eradication and reflux esophagitis and symptoms using a clearly defined set of inclusion criteria. Methods: We conducted a meta-analysis of studies published up until March 2020, which compared the incidence of reflux esophagitis and symptoms between patients undergoing H. pylori eradication therapy in a randomized placebo-controlled trial (Category A); between patients with successful and failed eradication (Category B); and between patients with successful vs. failed eradication, receipt of placebo, or no-treatment H. pylori-positives (Category C). Results: A total of 27 studies were included. Significant statistical effects were found for development of endoscopic reflux esophagitis [relative risk (RR): 1.46, 95% confidence interval (CI): 1.16–1.84, p = 0.01] or de novo reflux esophagitis (RR: 1.42, 95% CI: 1.01–2.00, p = 0.03) in the case group that received eradication in all studies, especially in Western populations. There was no significant difference in the incidence of symptoms after eradication between patient and control groups, regardless of category, location of population, or baseline disease. Conclusions: Eradication therapy for H pylori increases the risk of reflux esophagitis, irrespective of past history of esophagitis. In contrast, no effect was seen on reflux-related symptoms. Full article

Almost every kind of inflammation in the human body is accompanied by rising C-reactive protein (CRP) concentrations. This can include bacterial and viral infection, chronic inflammation and so-called sterile inflammation triggered by (internal) acute tissue injury. CRP is part of the ancient humoral immune response and secreted into the circulation by the liver upon respective stimuli. Its main immunological functions are the opsonization of biological particles (bacteria and dead or dying cells) for their clearance by macrophages and the activation of the classical complement pathway. This not only helps to eliminate pathogens and dead cells, which is very useful in any case, but unfortunately also to remove only slightly damaged or inactive human cells that may potentially regenerate with more CRP-free time. CRP action severely aggravates the extent of tissue damage during the acute phase response after an acute injury and therefore negatively affects clinical outcome. CRP is therefore a promising therapeutic target to rescue energy-deprived tissue either caused by ischemic injury (e.g., myocardial infarction and stroke) or by an overcompensating immune reaction occurring in acute inflammation (e.g., pancreatitis) or systemic inflammatory response syndrome (SIRS; e.g., after transplantation or surgery). Selective CRP apheresis can remove circulating CRP safely and efficiently. We explain the pathophysiological reasoning behind therapeutic CRP apheresis and summarize the broad span of indications in which its application could be beneficial with a focus on ischemic stroke as well as the results of this therapeutic approach after myocardial infarction. Full article

Connective tissue diseases (CTDs) are an important secondary cause of interstitial lung disease (ILD). If a CTD is suspected, clinicians are recommended to perform autoantibody testing, including for myositis autoantibodies. In this study, the prevalence and clinical associations of novel myositis autoantibodies in ILD are presented. A total of 1194 patients with ILD and 116 healthy subjects were tested for antibodies specific for Ks, Ha, Zoα, and cN1A with a line-blot assay on serum available at the time of diagnosis. Autoantibodies were demonstrated in 63 (5.3%) patients and one (0.9%) healthy control (p = 0.035). Autoantibodies were found more frequently in females (p = 0.042) and patients without a histological and/or radiological usual interstitial pneumonia (UIP; p = 0.010) and a trend towards CTD-ILDs (8.4%) was seen compared with other ILDs (4.9%; p = 0.090). The prevalence of antibodies specific for Ks, Ha, Zoα, and cN1A was, respectively, 1.3%, 2.0%, 1.4%, and 0.9% in ILD. Anti-Ha and Anti-Ks were observed in males with unclassifiable idiopathic interstitial pneumonia (unclassifiable IIP), hypersensitivity pneumonitis (HP), and various CTD-ILDs, whereas anti-cN1A was seen in females with antisynthetase syndrome (ASS), HP, and idiopathic pulmonary fibrosis (IPF). Anti-Zoα was associated with CTD-ILD (OR 2.5; 95%CI 1.11–5.61; p = 0.027). In conclusion, a relatively high prevalence of previously unknown myositis autoantibodies was found in a large cohort of various ILDs. Our results contribute to the awareness that circulating autoantibodies can be found in ILDs with or without established CTD. Whether these antibodies have to be added to the standard set of autoantibodies analysed in conventional myositis blot assays for diagnostic purposes in clinical ILD care requires further study. Full article

Background: This study aims to analyze the effect of physical activity practice on the postural control state of school children. If such an effect was detected, the second aim of the study was to identify which specific capacities of postural control benefited the most from physical activity. Methods: A cross-sectional study was performed using a convenience sample of 118 healthy children (54 girls) with a mean age of 10.3 ± 1.2 years. Their weight and height were measured. The accelerometric assessment of balance included four different tests in static balance and walking. Results: Physical activity habit prevalence was 38.9% in girls and 60.9% in boys, and its frequency was 2.3 days per week in girls and 2.8 days in boys. The active children obtained lower accelerations, but the active and sedentary girls showed lower accelerometric values than the active boys. The logistic regression analysis demonstrated the influence of sex on the accelerations of the body (p < 0.001), regardless of the habit of physical activity. Conclusions: Active children have better postural control than sedentary children, although sedentary girls have better balance than active boys. Therefore, physical activity practice seems to favor a more efficient development of postural control, but it cannot level or reverse the effect of the neurophysiological factors that are conditioned by sex. Full article