DiGeorge syndrome, an immunodeficiency disorder due to long arm microdeletion of chromosome 22. Isolated hemolysis is rarely seen in DiGeorge syndrome and is usually reported in conjunction with idiopathic thrombocytopenic purpura. We report a case of DiGeorge syndrome with AIHA, which was successfully managed by intravenous steroids and intravenous immunoglobulins.

Obstetric anal sphincter injury is a common complication of vaginal delivery. Such injuries are more likely to result in postpartum fecal incontinence and thus diagnosis and restoration of perineal injuries at the time of vaginal delivery is of paramount importance.

Background and Purpose: Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality and healthcare burden in the critically ill patient. There is an urgent medical need for identifying factors of susceptibility and prognosis and for designing new therapeutic tools for treating these disorders. Here, we evaluate the capacity of the immunomodulatory neuropeptide cortistatin to regulate pulmonary inflammation and fibrosis in vivo. Experimental Approach: ALI/ARDS and pulmonary fibrosis were induced experimentally in wild-type and cortistatin-deficient mice by pulmonary infusion of the bacterial endotoxin LPS or the chemotherapeutic drug bleomycin, and the histopathological signs, pulmonary leukocyte infiltration and cytokines and fibrotic markers were evaluated. Key Results: Partially-deficient mice in cortistatin showed exacerbated pulmonary damage, pulmonary inflammation, alveolar oedema and fibrosis, and subsequent increased respiratory failure and mortality when challenged to LPS or bleomycin, even at low doses. Treatment with cortistatin reversed these aggravated phenotypes and protected from progression to severe ARDS and fibrosis after high-exposition to both injury agents. Moreover, cortistatin-deficient pulmonary macrophages and fibroblasts showed exaggerated ex vivo inflammatory and fibrotic responses. The anti-fibrotic protective effect of cortistatin was also observed in experimental scleroderma, in which lack of cortistatin predisposes to develop more severe dermal lesions and associated pulmonary fibrosis. Conclusion and Implications: We identify to cortistatin as an endogenous break of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor-prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies emerge as attractive candidates to treat severe ALI/ARDS, including SARS-Cov-2-associated ARDS.

Northern range margin populations of the European fire-bellied toad (Bombina bombina) have rapidly declined during recent decades. Extensive agricultural land use has fragmented the landscape, leading to habitat disruption and loss, as well as eutrophication of ponds. In Northern Germany (Schleswig-Holstein) and Southern Sweden, this decline resulted in decreased gene flow from surrounding populations, low genetic diversity, and a putative reduction in adaptive potential, leaving populations vulnerable to future environmental and climatic changes. Previous studies using mitochondrial control region and nuclear transcriptome-wide SNP data detected introgressive hybridization in multiple northern B. bombina populations after presumed illegal release of toads from Austria. Here, we determine the impact of this introgression by comparing the body conditions (as a proxy for fitness) of introgressed and non-introgressed populations, and the genetic consequences in two candidate genes for putative local adaptation (the MHC II gene as part of the adaptive immune system and the stress response gene HSP70 kDa). We detected regional differences in body condition. We observed significantly elevated levels of within individual MHC allele counts in introgressed Swedish populations, associated with a tendency towards higher body weight, relative to regional non-introgressed populations. These differences were not observed among introgressed and non-introgressed German populations. Genetic diversity in both MHC and HSP was generally lower in northern than southern populations. Our study sheds light on the potential benefits of translocations of more distantly related conspecifics as a means to increase adaptive genetic variability and fitness of struggling range margin populations without distortion of local adaptation.

Accurate assessment of right ventricular (RV) function is drawing a growing attention. Pressure-volume (PV) loop analysis is the gold standard method for evaluating RV function; however, it is not widely employed due to its invasive nature and complexity. The present report is the first to have drawn a RV PV loop in a patient with pulmonary hypertension, with a simultaneous recording of RV pressure and volume using high fidelity micromanometry and 3D echocardiography. This allows for less invasive and simple assessment of RV function, potentially promoting better understanding and management of pulmonary hypertension and other cardiovascular diseases.

Introduction: The opinion that latent T. gondii infection is having a broadly asymptomatic projection has now been interrogated, in specific due to the echoed association between the latent infection and an elevated incidence of schizophrenia or even suicide attempts. Notwithstanding conducted studies aimed to understand this feasible link are restricted. Methods: In the present case-control study, we focused to illuminate the relationship between the serological and molecular presence of T. gondii and schizophrenia with or without the suicide attempts by comparing it with healthy individuals. A total of 237 participants (117 in schizophrenia; 120 in healthy control) were included in this study. Results: Overall, latent T. gondii infections were found statistically higher in 63 (53.8%) of the 117 patients with schizophrenia and in 33 (27.5%) of the 120 controls (p < 0.001). In schizophrenia patients, seroprevalence T. gondii was again found to be statistically higher in suicide attempters (59.6%), compared to no history of suicide attempts (48.3%) (p < 0.05). The molecular positivity rate of T. gondii DNA was higher in the schizophrenia group, compared to the healthy control group (p < 0.05), whereas the history of suicide attempts was not statistically associated (p = 0.831) with T. gondii DNA positivity by PCR. Conclusion: This case-control study enlightens additional demonstration to the belief that T. gondii infection would be an underlying component for the pathophysiology of schizophrenia. Regardless of the clarity results of this study, this supposition warrants further endorsement.

Phytoplasmas (Mollicutes, Acholeplasmataceae), vector-borne obligate bacterial plant-parasites, infect nearly 1,000 plant species and unknown numbers of insects, mainly leafhoppers (Hemiptera, Deltocephalinae), which play a key role in transmission and epidemiology. Although the plant-phytoplasma-insect association has been evolving for >300 million years, nearly all known phytoplasmas have been discovered as a result of the damage inflicted by phytoplasma diseases on crops. Few efforts have been made to study phytoplasmas occurring in non-economically important plants in natural habitats. In this study, a sub-sample of leafhopper specimens preserved in a large museum biorepository was analyzed to unveil potential new associations. PCR screening for phytoplasmas performed on 227 phloem-feeding leafhoppers collected worldwide from natural habitats revealed the presence of 6 different previously unknown phytoplasma strains. This indicates that museum collections of herbivorous insects represent a rich and largely untapped resource for discovery of new plant pathogens, that natural areas worldwide harbor a diverse but largely undiscovered diversity of phytoplasmas and potential insect vectors, and that independent epidemiological cycles occur in such habitats, posing a potential threat of disease spillover into agricultural systems. Larger-scale future investigations will contribute to a better understanding of phytoplasma genetic diversity, insect host range, and insect-borne phytoplasma transmission and provide an early warning for the emergence of new phytoplasma diseases across global agroecosystems.

Background Pharmacotherapies are widely used for smoking cessation. However, their effect on smoking cessation for people with alcohol dependence remains unclear. Objective This study aimed to explore the effects of pharmacotherapies on smoking cessation for people with alcohol dependence. Methods Five electronic databases were searched in January 2021 for randomized controlled trials (RCTs) reporting the use of pharmacotherapies to promote smoking cessation in people with alcohol dependence. The risk of bias was assessed using the Cochrane tool. RevMan version 5.3 was used to perform meta-analyses of the changes in smoking behavior, and the GRADE approach was used to assess the certainty of the evidence. Results Nine RCTs involving 908 smokers with alcohol dependence were identified. Eight RCTs were published in the United States, and one was from Canada. The risk of bias was rated as low in three studies and unclear in the remaining six. The results of the meta-analysis showed that, compared with the placebo group, Varenicline had a significant effect on short-term smoking cessation (three RCTs, OR = 6.27, 95% CI: [2.49, 15.78], p < 0.05, very low certainty). Naltrexone had no significant effect on smoking cessation in short-term or long-term observations (three RCTs, OR = 0.99, 95% CI: [0.54, 1.81], p = 0.97, moderate certainty), and Topiramate had no significant effect (two RCTs, OR = 1.56, 95% CI: [0.67, 3.46], p > 0.05, low certainty). Only one trial reported that Bupropion had no effect on smoking cessation. Conclusion Varenicline may have a positive effect on smoking cessation in people with alcohol dependence. However, Naltrexone, Topiramate, and Bupropion seem to have no clear effect on increasing smoking abstinence among drinkers. The small number of studies and the low certainty of evidence indicate that caution is required in interpreting the results.

In 2020, we had reported one of the few cases of trisomy 13 with ectrodactyly, a rare form of limb deformity. Herein, we report another newborn who suffered from trisomy 13 and ectrodactyly. The patient also possessed another unusual manifestation of trisomy 13, congenital diaphragmatic hernia, a life- threatening pathology.

Objectives One important group of people at higher risk from the COVID-19 pandemic are those with autoimmune conditions including rheumatoid arthritis/inflammatory bowel disease. To minimise infection risk, many people are now being switched from intravenous to subcutaneous biologics including biosimilars. A key question is how transition costs are viewed by clinicians. Design The survey was designed to understand the comparative economic issues related to the intravenous infusion vs subcutaneous biologic administration routes for infliximab. The survey focused on direct cost drivers/indirect cost drivers. Wider policy implications linked to the pandemic were also explored. Setting/Participants Semi structured telephone interviews were carried out with twenty key stakeholders across the NHS from clinical/pharmacy/commissioning roles. The interviews were undertaken virtually 5thApril-27thApril 2020 and included a semi-structured interview framework with questions across the two administration routes. Results From interview results a simple cost analysis was developed plus a qualitative analysis of reports on wider policy/patient impacts. Key findings included evidence of significant variation in infusion tariffs UK wide, with interviewees reporting that not all actual costs incurred are captured in published tariff costs. A cost analysis showed administration costs 50% that of infusion, with a most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times and reduced risk of COVID-19 infection plus reduced patient costs. However, this was to some extent offset by increased pressure on home-care and community/primary care services. Conclusions Switching from infusion to subcutaneous routes is currently being driven by the COVID-19 pandemic in many services. A case for biologics (infusion vs subcutaneous) must be made on accurate real-world economic analysis. In an analysis of direct/indirect costs, excluding medicine acquisition costs, subcutaneous administration appears to be the more cost saving option for many patients even without the benefit of industry funded home-care.

Arrhythmia Induced Cardiomyopathy: What are Predictors of Myocardial Recovery?Acile Nahlawi BS, Marwan M. Refaat MDDepartment of Internal Medicine, Division of Cardiology, American University of Beirut Medical Center, Beirut, LebanonRunning Title: AIC and Predictors of Myocardial RecoveryDisclosures: NoneFunding: NoneKeywords: Cardiac Arrhythmias, Cardiovascular Diseases, Heart Diseases, Congestive Heart Failure, CardiomyopathyWords: 958 (excluding references)Correspondence:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FRCPAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonFax: +961-1-370814Clinic: +961-1-759616 or +961-1-355500 or +961-1-350000/+961-1-374374 Extension 5800Office: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: [email protected] cause a significant public health burden and improvement in sudden cardiac death risk stratification helped in decreasing mortality by improved pharmacotherapy as well as device implantations including implantable cardiac defibrillators and cardiac resynchronization therapy [1-4]. Arrhythmia induced cardiomyopathy (AIC) is a major cause of non-ischemic cardiomyopathy and heart failure (HF) worldwide [5]. It is characterized by an impairment of left ventricular systolic function secondary to high heart rate (tachycardia-induced), asynchrony (frequent premature ventricular contractions-induced or right ventricular pacing-induced) or an irregular rhythm (such as atrial fibrillation-induced) that serves as the trigger of AIC and this is mediated by calcium mishandling. The distinctive feature of AIC is the substantial improvement in left ventricular systolic function following arrhythmia suppression or elimination [5]. Atrial Fibrillation (AF) is concomitantly present with and potentially the cause of 10 to 50% of HF cases [6]. AIC is an important, commonly encountered and potentially reversible entity that is often under-recognized. The exact incidence and prevalence of AIC remains poorly defined in the literature [7]. In some studies, it was present in as high as 50% of patients with AF undergoing ablation, while it was reported to be present in 10% of patients with focal atrial tachycardia undergoing ablation [8]. In addition, very little attention, if any, is given to AIC in major trials on AF and HF, despite its significant implications on morbidity and mortality and the promising benefits of treatment [7]. Many aspects of AIC are yet to be understood. In fact, few studies limited by small sample size constitute our main source of knowledge on extent and predictors of ventricular recovery after treatment initiation in patients with AIC [9,10].In their multicenter retrospective study, Gopinathannair et al. aimed to assess the degree of recovery of the left ventricular systolic function after suppression/elimination of the underlying arrythmia and to evaluate factors influencing this response such as baseline patient and arrhythmia characteristics. The study sample comprised 243 patients from 3 different institutions whose charts were reviewed retrospectively (no recruitment timeframe was indicated). The patient characteristics studied included baseline left ventricular ejection fraction (LVEF), presence of structural heart disease (SHD) [ defined as significant coronary artery disease, prior myocardial infarction, hemodynamically significant valvular heart disease, or other structural cardiomyopathies] and medications used. As for the arrhythmia characteristics, they included arrhythmia duration and arrhythmia type. The authors used echocardiography as the imaging modality to determine extent of ventricular function recovery by comparing myocardial function before and after treatment of the culprit arrhythmia. The echocardiographic parameters that were assessed included LVEF, LV end-diastolic and end-systolic diameters, left atrial dimension, valvular abnormalities, right ventricular systolic pressures, and pulmonary arterial pressures.In contrast to reported literature on the topic, Gopinathannair et al. found that none of the studied patient and arrhythmia characteristics had a significant effect on the recovery of ventricular function. Their results showed that initiation of aggressive arrhythmia treatment is warranted in patients with suspected AIC, regardless of arrhythmia duration, arrhythmia type, severity of baseline LVEF, and underlying structural heart disease. This was concluded based on the consistent substantial improvement in LVEF after arrhythmia suppression/elimination, mainly through rhythm control, across all different subgroups. In fact, the extent of LVEF improvement was similar whether comparing the group with known arrhythmia duration [KN] to that with unknown arrhythmia duration [UKN] (21.2±9 % vs 19.4±11 %, p-value =0.16) or comparing the group with longest arrhythmia duration to the rest (21.5±7.5 % vs 21.0 ± 9.2%, p-value=0.77). On the other hand, greatest improvement was seen in the group with lowest initial LVEF (24±17 vs 19±7%; p-value <0.0001), making low index LVEF the only predictor of LVEF recovery after arrhythmia treatment in patients with AIC. However, the LVEF in these patients did not reach complete normalization; they had lower post-treatment LVEF compared to other groups (45±14 vs 54±8%; p<0.0001), a finding consistent with the available literature. Also similar to previous studies, the authors found that patients with PVCs experienced smaller extent of recovery compared to other arrhythmia types. The authors concluded by stressing the importance of suspecting AIC in patients having cardiomyopathy with a persistent arrhythmia and initiating aggressive arrhythmia treatment regardless of initial patient and arrhythmia characteristics.As for the limitations of the study by Gopinathannair et al., there are few to mention. First, the study had a retrospective design and therefore findings only serve to generate hypotheses that need further testing and validation. Second, there is a lack of a control group to exclude interference of confounding factors. Although the use of Angiotensin-Converting Enzyme inhibitors (ACEi)/ Angiotension receptor blockers (ARB) did not independently predict LVEF improvement in multivariate analysis, it could still be a confounder given the lower rates of ACEi/ARB use in the cohort. Third, the timeframe of the study and the period of follow-up were not clearly defined. Fourth, there is lack of blinding of echocardiographic analyses which can potentially lead to inter- and intra-observer variability. Finally, the sample population was not diverse as it consisted in its majority of Caucasians.The Gopinathannair et al. study demonstrated several points of strength. Among these are its multicenter nature and its relatively larger sample size compared to similar studies, giving its findings more weight. Moreover, the authors appropriately and clearly defined their inclusion and exclusion criteria. Furthermore, no funding was needed for the study which potentially frees it from direct or indirect influences on its design, execution and interpretation. Finally, the study has successfully improved our understanding of predictors of ventricular recovery in patients with AIC and showed that patients with AIC who had the longest duration of arrhythmia still had LV systolic function improvement with arrhythmia suppression/elimination. This study paves the way for prospective studies and randomized clinical trials to validate the generated hypotheses and corroborate the observational findings.

Periodic chest pain, with bloody pleural effusion, should raise the suspicion of pleural endometriosis as a well-known, but rare condition in clinical practice.

A 49-year-old woman presented to the emergency department with dyspnea, a respiratory rate of 26 times per minute and a room air oxygen saturation of 69% after nasal inhalation of heroin. A chest computed tomography angiogram (CTA) revealed diffuse ground-glass opacities in all five lung lobes representing hypersensitivity pneumonitis

OBJECTIVE The aim of this study is to describe our short-term outcomes using BioIntegral pulmonic conduit. METHODS Between August 2018 and September 2019, the BioIntegral pulmonic valved conduit was used for right ventricular outflow tract reconstruction in 48 patients. The data was retrospectively retrieved from the patient charts. RESULTS The median age at the operation was 36 months (IQR:18-62 months). The diagnoses were PA-VSD in 28 patients, absent pulmonary valve in four patients, truncus arteriosus in six patients, TGA-VSD-PS in five patients, conduit stenosis in three patients and LVOT obstruction requiring Ross operation in two patients. In the postoperative follow-up 15 patients out of 48 had high fever. Out of these, 12 patients had concomitantly elevated CRP levels. There were no patients with blood culture positivity. The median postoperative length of hospital stay was 14 days (IQR:8-21 days). The overall mortality was recorded in 2 patients (4 %), one died due to right ventricular failure and multiple organ failure and one died due to pulmonary embolism. The two patients who died were not among the 15 patients with fever. CONCLUSIONS There was high incidence of fever and adverse outcomes in the short-term postoperative follow-up of the patients in whom the BioIntegral pulmonic valved conduit was implanted. Caution is advisable in using these conduits until there is convincing evidence about the sterilisation and storage standards of these grafts.

Current knowledge on environmental distribution and taxon richness of free-living bacteria is mainly based on cultivation-independent investigations employing 16S rRNA gene sequencing methods. Yet, 16S rRNA genes are evolutionarily rather conserved, resulting in limited taxonomic and ecological resolutions provided by this marker. We used a faster evolving protein-encoding marker to reveal ecological patterns hidden within a single OTU defined by >99% 16S rRNA sequence similarity. The studied taxon, subcluster PnecC of the genus Polynucleobacter, represents a ubiquitous group of planktonic freshwater bacteria with cosmopolitan distribution, which is very frequently detected by diversity surveys of freshwater systems. Based on genome taxonomy and a large set of genome sequences, a sequence similarity threshold for delineation of species-like taxa could be established. In total, 600 species-like taxa were detected in 99 freshwater habitats scattered across three regions representing a latitudinal range of 3400 km (42°N to 71°N) and a pH gradient of 4.2 to 8.6. Besides the unexpectedly high richness, the increased taxonomic resolution revealed structuring of Polynucleobacter communities by a couple of macroecological trends, which was previously only demonstrated for phylogenetically much broader groups of bacteria. A unexpected pattern was the almost complete compositional separation of Polynucleobacter communities of Ca2+-rich and Ca2+-poor habitats, which strongly resembled the vicariance of plant species on silicate and limestone soils. The presented new cultivation-independent approach opened a window to an incredible, previously unseen diversity, and enables investigations aiming on deeper understanding of how environmental conditions shape bacterial communities and drive evolution of free-living bacteria.

COVID-19 can present with lymphopenia and extraordinary complex multi-organ pathologies that can trigger long-term sequela. Given that inflammasome products, like caspase-1, play a role in the pathophysiology of a number of co-morbid conditions, we investigated caspases across the spectrum of COVID-19 disease. We assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of disease. Non-COVID-19 subjects presenting with various co-morbid conditions served as controls. Single-cell RNA-seq data of immune cells from COVID-19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells and eosinophils compared to controls. Caspase-1 was upregulated in CD4+ T-cells from hospitalized COVID-19 patients compared to unexposed controls. Post-COVID-19 patients with lingering symptoms (long-haulers) also showed up-regulated caspase-1 activity in CD4+ T-cells that ex vivo was attenuated with a select pan-caspase inhibitor. We observed elevated caspase-3/7 levels in red blood cells from COVID-19 patients compared to controls that was reduced following caspase inhibition. Our preliminary results suggest an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID-19 will be needed. Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared to the standard of care. Pubmed, EMBASE and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, reslizumab-1) included 1236 adults, with follow-up 20-64 weeks. Dupilumab reduces the need for surgery (NFS) and oral corticosteroid (OCS) use (RR 0.28; 95%CI 0.20-0.39, moderate certainty) and improves with high certainty smell (mean difference (MD) +10.54; 95%CI +9.24 to +11.84) and quality of life (QoL) (MD -19.14; 95%CI 95%CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95%CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95%CI 0.78 to 0.92, high certainty), decreases OCS use (RR 0.38; 95%CI 0.10-1.38, moderate certainty), improves with high certainty smell (MD +3.84; 95%CI +3.64 to +4.04) and QoL (MD -15.65; 95%CI -16.16 to -15.13), with increased TAE (RR 1.73; 95%CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95%CI 0.64 to 0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95%CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95%CI 0.41-6.50). The evidence for reslizumab is very uncertain.

This short note corrects minor mistakes in the original paper.