Utilizing ambulatory electrocardiogram monitoring to reduce conduction related death after transcatheter aortic valve replacement.

OBJECTIVE: The purpose of this study is to assess the utility of ambulatory cardiac monitoring (ACM) in detecting delayed advanced conduction abnormalities (DACA) and associated 30-day mortality. BACKGROUND: DACA are well-known complications of TAVR and may be associated with post-discharge mortality within 30-days. METHODS: Between October 2019 and October 2020, TAVR patients who were discharged home without a permanent pacemaker (PPM) were monitored with an ACM device for 14-days. The incidence of DACA at follow up, mortality and readmission within 30-days were investigated. The risk of DACA was assessed in three patient categories based on a composite of their 12-lead electrocardiogram (ECG) data. Group I: Normal pre-TAVR, periprocedural, and discharge ECGs. Group II: Normal pre-TAVR and abnormal subsequent ECGs. Group III. Abnormal baseline and abnormal subsequent ECGs. RESULTS: Among 340 TAVR patients, 248 were discharged home with an ACM device. The overall incidence of DACA was 7% (n = 17), of whom 4% (n = 10) required a PPM. Mortality and readmission between discharge and 30 days was 0% and 8.3%, respectively. Stratification of patients identified 96 (38.7%) patients in Group I: 50 (20%) in Group II, and 102 (41%) in Group III. The incidence of DACA requiring a PPM was 0% in Group I, 4% (n = 2) in Group II, and 8.5% (n = 8) in Group III (p < 0.004). CONCLUSIONS: In TAVR patients who were discharged home with ACM, none died between discharge and 30-days. For those with normal baseline, perioperative and discharge ECG, there were no events of DACA at 14-days.

Expanding donor pool for live donor liver transplantation: utilization of donors with non-alcoholic steatohepatitis after optimization.

INTRODUCTION: Potential live liver donors with non-alcoholic steatohepatitis (NASH) are rejected upfront for donation in live donor liver transplantation (LDLT). Herein, we share our experience of the feasibility of live liver donation in donors with NASH after successful donor optimization. MATERIALS AND METHODS: Prospectively collected data of 410 consecutive donor hepatectomies from June 2011 to January 2018 were analyzed. RESULTS: During the study period, NASH was diagnosed histopathologically in 17 donors. Four donors were rejected in view of grade 2 fibrosis on histology. Out of remaining 13 donors, six became eligible for donation following lifestyle changes, dietary modifications, and target weight reduction of ≥5%. Reversal of NASH was confirmed on repeat liver biopsy in all the 6 donors. Five out of 6 underwent right lobe (without MHV) donor hepatectomies, while one had left lobe donation. These donors had significantly higher peak bilirubin levels in the immediate post-operative period as compared to other non-NASH donors (4.00 ± 0.32 vs. 2.57 ± 1.77 mg/dL, p = 0.043). In addition, post-hepatectomy normalization of hyperbilirubinemia, if any, was slower in donors with NASH (7 ± 1.3 vs. 5 ± 1.7 days, p = 0.016). However, none of these donors had post-hepatectomy liver failure. All these donors were discharged after an average hospital stay of 8 ± 1.7 days. Their respective recipients had uneventful post-operative courses without complications. Both the recipients and donors are having satisfactory liver functions after 46.7 ± 10.2 months of follow-up. CONCLUSION: Scrupulous selection of live liver donors with NASH can open a door for expanding the organ pool in LDLT after a successful donor optimization program.

Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis.

BACKGROUND: Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived extracellular vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. METHODS: Immune cell-derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n = 15; B n = 16; C n = 43 and Child-C with sepsis (n = 38)], and healthy controls (HC, n = 11). In vitro and in vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. RESULTS: Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (P < .001)and correlated with liver disease severity indices (r2  > 0.3, P < .001), which further increased in Child C sepsis than without sepsis(P < .001); monocyte EV showing the highest association with disease stage [P = .013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio-6.2 (2.4-15.9), AUROC = 0.76, P < .01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (P = .004), reduced basal oxygen consumption rate (P < .001) and induced pro-inflammatory genes (P < .05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis-like condition within 24 h with leukocytopenia (P = .005), intrahepatic inflammation with increased CD11b + cells (P = .03) and bone marrow hyperplasia (P < .01). CONCLUSION: Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients.

Does the Presence of Significant Mitral Regurgitation prior to Transcatheter Aortic Valve Implantation for Aortic Stenosis Impact Mortality? - Meta-Analysis and Systematic Review.

BACKGROUND: Mitral regurgitation (MR) is commonly encountered in patients with severe aortic stenosis (AS). However, its independent impact on mortality in patients undergoing transcatheter aortic valve implantation (TAVI) has not been established. METHODS: We performed a systematic search for studies reporting characteristics and outcome of patients with and without significant MR and/or adjusted mortality associated with MR post-TAVI. We conducted a meta-analysis of quantitative data. RESULTS: Seventeen studies with 20,717 patients compared outcomes and group characteristics. Twenty-one studies with 32,257 patients reported adjusted odds of mortality associated with MR. Patients with MR were older, had a higher Society of Thoracic Surgeons score, lower left ventricular ejection fraction, a higher incidence of prior myocardial infarction, atrial fibrillation, and a trend towards higher NYHA class III/IV, but had similar mean gradient, gender, and chronic kidney disease. The MR patients had a higher unadjusted short-term (RR = 1.46, 95% CI 1.30-1.65) and long-term mortality (RR = 1.40, 95% CI 1.18-1.65). However, 16 of 21 studies with 27,777 patients found no association between MR and mortality after adjusting for baseline variables. In greater than half of the patients (0.56, 95% CI 0.45-0.66) MR improved by at least one grade following TAVI. CONCLUSION: The patients with MR undergoing TAVI have a higher burden of risk factors which can independently impact mortality. There is a lack of robust evidence supporting an increased mortality in MR patients, after adjusting for other compounding variables. MR tends to improve in the majority of patients post-TAVI.

PbS nanosculptured thin film for phase retarder, anti-reflective, excellent absorber, polarizer and sensor applications.

Lead-sulphide (PbS) nanosculptured thin film (nSTF) is prepared using a glancing angle deposition (GLAD) technique and the physical vapour deposition (PVD) process. The morphology of the GLAD films clearly shows that an anisotropic structure is obtained and is composed of micro-sheets with sharp top edges (a few tens of nanometres tip width). Due to this anisotropy, optical birefringence is induced in the nSTF as well as linear dichroism. The structural and optical properties of the PbS nSTF have been characterized by scanning electron microscopy, atomic force microscopy, Raman spectroscopy and transmission measurements. The Raman spectra of PbS nSTF exhibit sharp peaks representative of vibrations in nano-crystalline PbS. Due to the absorption of PbS the nSTF is found to act as a linear polarizer with good extinction and contrast in the near infra-red range. Due to its porosity this nSTF also has the ability to sense fluids, which we demonstrate using ethanol-water solution at different concentrations. The combination of these effects in PbS nSTF is believed to constitute a prime candidate for many desirable device applications in different aspects with the low cost of production in large areas.

Evaluation of Trends of Inpatient Hospitalisation for Significant Haemorrhage in Patients Anticoagulated for Atrial Fibrillation before and after the Release of Novel Anticoagulants.

Compared to Vitamin K antagonists (VKA), novel oral anticoagulants (NOACs) appear to be safer in terms of major bleeding risks with added advantage of having fixed dosing schedules when used in patients with non-valvular atrial fibrillation (AF). We sought to study the differences as sources and severity of anticoagulant-associated haemorrhage in patients with AF in the year preceding introduction of NOACs (first cohort) as compared to post approval of the NOACs (second cohort) by retrospectively reviewing the hospital admissions, as well as the pharmacodynamic and pharmacokinetic interactions between time periods. There were 359 patients for the first cohort and 405 patients for the second cohort, including 57 patients prescribed NOACs. There was no significant difference in age, deaths, source of bleeding, or rate of pharmacokinetic or pharmacodynamic interaction between the two time periods. Comparing all VKA patients to patients prescribed NOAC's, there were non-significant but higher rates of intracerebral bleed, significantly higher rates of pharmacokinetic (194 (25.4%) versus 0 (0%), p<.001) and similar rates of pharmacodynamic interactions (505 (66.1%) versus 39 (68.4%), p=.70). Drug-renal interactions were seen in 7 of the 57 (12.3%) NOAC-treated patients, in which all seven had acute renal failure that may have prolonged the effects of the anticoagulants. NOACs hold promise in that drug interactions are far less common than those seen in VKAs, and intracerebral bleeds appear to be less common in randomised trials as well as our review. For patients on dabigatran or rivaroxaban, consideration should be given to serial monitoring of renal function.

Role of NADPH oxidase and xanthine oxidase in mediating inducible VT/VF and triggered activity in a canine model of myocardial ischemia.

BACKGROUND: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF. METHODS: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV), oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or standard microelectrode techniques. Results (mean±SE, * p<0.05): VT/VF originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated myocardium, TA was blocked by APO (10(-6) M) or OXY (10(-8) M). Rac1 levels in ischemic endocardium were decreased by APO or OXY. CONCLUSION: APO and OXY suppressed focal VT/VF due to DADs, but the combination of the drugs was not more effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF suggests that other mechanisms also contribute to ischemic VT.

Patients undergoing emergent surgery for type A intramural hematomas or type A aortic dissections have similar outcomes.

OBJECTIVE: Despite key differences in pathological processes, both Intramural Hematomas and Aortic Dissections are Acute Aortic Syndromes repaired with similar surgical technique. The objective of this study was to determine differences in surgical outcomes between patients with Intramural Hematoma versus Type A Aortic Dissection undergoing Ascending Aortic Arch repair. METHODS: This retrospective review of prospectively collected data included all patients with acute Intramural Hematoma or Type A Aortic Dissection who underwent emergent Ascending- or Arch Repair from January 2018 to May 2023 at a single academic institution. Primary outcomes included intraoperative mortality, 30-Day mortality, and postoperative stay. Secondary outcomes included postoperative complications. Outcomes were analyzed using Chi-squared, Fisher's Exact, and t-tests, with significance set at p < 0.05. RESULTS: A total of 107 patients were included, 27 of whom (25%) had Intramural Hematoma and 80 (75%) had Type A Aortic Dissection. There were no differences in preoperative characteristics such as age, gender, and comorbidities, and no differences in perioperative characteristics such as case length, cardiopulmonary bypass, aortic cross-clamp, and circulatory arrest times. When comparing postoperative outcomes, there was a higher rate of postoperative pericardial effusions requiring pericardial window in the Intramural Hematoma cohort compared to the Aortic Dissection cohort (15% [n = 4] vs. 3% [n = 2]; p = 0.02). There were no differences in other primary outcomes such as intraoperative mortality, 30-Day mortality, and postoperative length of stay. There were also no differences in the rates of postoperative complications such as bleeding requiring reoperation, cerebrovascular accident, atrial fibrillation, pleural effusion requiring thoracentesis, and surgery-related Emergency Department visits. CONCLUSIONS: Our analysis demonstrates similar outcomes for patients undergoing Ascending Aortic Arch repair between patients with Intramural Hematoma and Type A Aortic Dissection. Despite the higher rate of required postoperative pericardial windows in the Intramural Hematoma cohort, the overall primary outcomes remained comparable. These findings better elucidate the standard of care for patients with acute Intramural Hematoma undergoing Ascending Aortic Arch repair.

Establishment of human post-vaccination SARS-CoV-2 standard reference sera.

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.

Transcatheter aortic valve replacement among heart transplant recipients with donor aortic valve diseases: a systematic review of the literature.

BACKGROUND: Despite high surgical risk among heart transplant (HTx) recipients, who develop aortic valve diseases (AVD), transcutaneous aortic valve replacement (TAVR) has been scarcely reported as a viable option in this patient population. METHODS: A systematic review was conducted to identify studies reporting the outcomes of HTx recipients who developed AVD of the donor heart and underwent TAVR. Studies were eligible if they provided individual-level data for HTx recipients, who underwent TAVR on the donor heart. Review articles, editorials or commentaries, studies lacking original data, or those reporting surgical valve replacement for AVD in HTx recipients were excluded. RESULTS: A total of 15 case reports, encompassing 15 patients, describing characteristics and outcomes of HTx recipients undergoing TAVR were included. These included 13 males and 2 females with an average age of 63.6±15 years. The indications for HTx were non-ischemic dilated cardiomyopathy, ischemic cardiomyopathy and ischemic dilated cardiomyopathy in 42.9%, 35.7%, and 21.4% of the patients, respectively. The main indication for aortic valve replacement (AVR) among HTx recipients was aortic stenosis (73.3%). The transcutaneous approach was preferred over surgical AVR due to high surgical risk in > 50% of the patients. Both pre-TAVR transvalvular pressure gradient and the peak aortic pressure gradient decreased after the TAVR. Paravalvular leak was minimal/none to mild in all the patients post-TAVR. Most patients had an uneventful post-TAVR recovery with no recurrence of the symptoms or echocardiographic finings at a median follow-up of 6 months. CONCLUSIONS: TAVR seems to be a viable option for HTx recipients who develop donor aortic valve diseases. However, there is a paucity of knowledge on the long-term survivability of the replaced aortic valves and the clinical and echocardiographic outcomes of HTx recipients undergoing TAVR.

Identification and characterization of probiotics isolated from indigenous chicken (Gallus domesticus) of Nepal.

BACKGROUND: Excessive and irrational use of antibiotics as growth promoters in poultry has been one of key factors contributing to increased emergence of antibiotics resistant bacteria. Several alternatives for antibiotic growth promoters are being sought, and the search for effective probiotics to be used as feed additives is amongst the promising ones. Our study aimed to isolate and test potential probiotics bacteria from cloacal swabs of various indigenous chicken (Gallus domesticus) breeds from rural outskirts of the Kathmandu valley (Nepal). METHODS: Selective isolation of probiotics was conducted by micro-aerophilic enrichment of sample in MRS Broth at 37°C, followed by culturing on MRS agar supplemented with 5 g/L of CaCO3. Isolated bacterial colonies producing transparent halo were selected as potential lactic acid bacteria (LAB), and tested for their antibacterial activity, phenotypic and biochemical characteristics, acidic yield, and tolerance to acid and bile. RESULTS: A total of 90 potential LAB were isolated from cloacal samples collected from 41 free-ranging chickens of indigenous breeds. Of these, 52 LAB isolates (57%) showed variable antibacterial activity to at least one bacterial pathogen. Of 52 LAB, 46 isolates fulfilled phenotypic and biochemical criteria of Lactobacillus spp. Of these, 37 isolates produced varying percentage yields of lactic acid, 27 isolates showed survival at pH 3.0, and 17 isolates showed survival tolerances in the presence of 0.3% and 0.5% bile salts for 24 hours. Phylogenetic analysis of 16S rDNA sequencing of LAB isolates fulfilling in vitro probiotics properties showed that 3 isolates had genetic identity of 99.38% with Lactobacillus plantarum, while one isolate was genetically similar (99.85%) with the clade of L. reuteri, L. antri and L. panis. CONCLUSION: Our study identified four Lactobacillus spp. strains having potential probiotics properties. Further investigations are needed to evaluate these isolates to be used as poultry probiotics feed supplement.

Novel strains of Campylobacter cause diarrheal outbreak in Rhesus macaques (Macaca mulatta) of Kathmandu Valley.

Campylobacter spp. is often underreported and underrated bacteria that present real health risks to both humans and animals, including non-human primates. It is a commensal microorganism of gastrointestinal tract known to cause gastroenteritis in humans. Commonly found in many wild animals including non-human primates (monkeys- Rhesus macaques) these pathogens are known to be a common cause of diarrhea in humans in many parts of developing and under developed countries. Rhesus macaques from the two holy sites in Kathmandu (Pashupati and Swoyambhu) were included in this cross-sectional study. Diarrheal samples of monkeys were analyzed to detect and characterize the pathogen using 16S rRNA-based PCR screening, followed by DNA sequencing and phylogenetic analysis. Out of a total 67 collected diarrheal samples, Campylobacter spp. were detected in the majority of the samples (n = 64; 96%). DNA sequences of the amplified PCR products were successfully obtained from 13 samples. Phylogenetic analysis identified Candidatus Campylobacter infans (n = 10, Kimura-2 parameter (K2P) pairwise distance values of 0.002287). Remaining three sequences might potentially belong to a novel Campylobacter species/sub-species- closely relating to known species of C. helviticus (K2P pairwise distance of 0.0267). Both Candidatus Campylobacter infans and C. helvitucus are known to infect humans and animals. Additionally, we also detected the bacteria in water and soil samples from the sites. Campylobacter spp. caused the 2018 diarrhea outbreak in Rhesus macaques in the Kathmandu valley. Campylobacter might be one of the important contributing pathogens in diarrheal outbreaks-both in humans and animals (monkeys) in Nepal. Due to close interactions of these animals with humans and other animals, One Health approach might be the most effective way to prevent and mitigate the threat posed by this pathogen.

Rapid genomic surveillance of SARS-CoV-2 in a dense urban community of Kathmandu Valley using sewage samples.

Understanding disease burden and transmission dynamics in resource-limited, low-income countries like Nepal are often challenging due to inadequate surveillance systems. These issues are exacerbated by limited access to diagnostic and research facilities throughout the country. Nepal has one of the highest COVID-19 case rates (915 cases per 100,000 people) in South Asia, with densely-populated Kathmandu experiencing the highest number of cases. Swiftly identifying case clusters (hotspots) and introducing effective intervention programs is crucial to mounting an effective containment strategy. The rapid identification of circulating SARS-CoV-2 variants can also provide important information on viral evolution and epidemiology. Genomic-based environmental surveillance can help in the early detection of outbreaks before clinical cases are recognized and identify viral micro-diversity that can be used for designing real-time risk-based interventions. This research aimed to develop a genomic-based environmental surveillance system by detecting and characterizing SARS-CoV-2 in sewage samples of Kathmandu using portable next-generation DNA sequencing devices. Out of 22 sites in the Kathmandu Valley from June to August 2020, sewage samples from 16 (80%) sites had detectable SARS-CoV-2. A heatmap was created to visualize the presence of SARS-CoV-2 infection in the community based on viral load intensity and corresponding geospatial data. Further, 47 mutations were observed in the SARS-CoV-2 genome. Some detected mutations (n = 9, 22%) were novel at the time of data analysis and yet to be reported in the global database, with one indicating a frameshift deletion in the spike gene. SNP analysis revealed possibility of assessing circulating major/minor variant diversity on environmental samples based on key mutations. Our study demonstrated the feasibility of rapidly obtaining vital information on community transmission and disease dynamics of SARS-CoV-2 using genomic-based environmental surveillance.

Predictive accuracy of ST depression during rapid atrial fibrillation on the presence of obstructive coronary artery disease.

BACKGROUND: Rapid atrial fibrillation (AF) is commonly associated with ST-segment depressions. ST-segment depression during a chest pain episode or exercise stress testing in sinus rhythm is predictive of obstructive coronary artery disease (CAD), but it is unclear if the presence or magnitude of ST-segment depression during rapid AF has similar predictive accuracy. METHODS: One hundred twenty-seven patients with rapid AF (heart rate ≥120 beats per minute) who had cardiac catheterization performed during the same hospital admission were retrospectively reviewed. Variables to compute thrombolysis in myocardial infarction (TIMI) risk score, demographic profiles, ST-segment deviation, cardiac catheterization results, and cardiac interventions were collected. RESULTS: Thirty-five patients had ST-segment depression of 1 mm or more, and 92 had no or less than 1 mm ST depression. Thirty-one patients were found to have obstructive CAD. In the group with ST-segment depression, 11 (31%) patients had obstructive CAD and 24 (69%) did not. In the group with less than 1 mm ST-segment depression, 20 (22%) had obstructive CAD and 72 (78%) did not (P = .25). Sensitivity, specificity, and positive and negative predictive values for presence of obstructive CAD were 35%, 75%, 31%, and 78%, respectively. The presence of ST-segment depression of 1 mm or more was not associated with presence of obstructive CAD before or after adjustment of TIMI variables. The relationship between increasing grades of ST-segment depression and obstructive CAD showed a trend toward significance (P = .09), which did not persist after adjusting for TIMI risk variables (P = .36). CONCLUSION: ST-segment depression during rapid AF is not predictive for the presence of obstructive CAD.

Immune Response to SARS-CoV-2 Vaccine among Heart Transplant Recipients: A Systematic Review.

Background: Heart transplant (HTX) recipients are at a significantly higher risk of adverse clinical outcomes, due to chronic immunosuppression and co-existence of other chronic conditions, when contracting the SARS-CoV-2 infection. Although vaccination against SARS-CoV-2 is currently the most promising measure for the prevention of severe Coronavirus Disease 2019 (COVID-19) among solid organ transplant recipients, the extent of immune response and its protective efficacy among patients receiving HTX has not been sufficiently studied. Methods: We performed a systematic review of the literature by inquiring PubMed/Medline to identify original studies among HTX recipients, who had received at least one dose of the SARS-CoV-2 vaccine. Data on the measured humoral or cellular immune response was collected from all the eligible studies. Factors associated with a poor immune response were further investigated within these studies. Results: A total of 12 studies comprising 563 HTX recipients were included. The average age of the study participants was 60.8 years. Sixty four percent of the study population were male. Ninety percent of the patients had received an mRNA vaccine (Pfizer/ BNT162b2 or Moderna/mRNA-1273). A positive immune response to SARS-CoV-2 vaccine was variably reported in 0% to 100% of the patients. Older age (> 65 years), vaccine dose (first, second, or third), time since HTX to the first dose of the vaccine, the time interval between the latest dose of the vaccine and measurement of the immune response, and the type of immunosuppressive regimen were all indicated as potential determinants of a robust immune response to the SARS-CoV-2 vaccination. Conclusion: HTX recipients demonstrate a weaker immune response to the vaccination against SARS-CoV-2 compared to the general population. Older age, anti-metabolite agents such as mycophenolate mofetil, and vaccination during the first year following the HTX have been indicated as potential determinants of a poor immune response.

Characteristics and outcomes of hospitalized adults with COVID-19 in Nepal: a multicenter, prospective cohort study.

INTRODUCTION: There is limited data on clinical course and outcomes of hospitalized adults with COVID-19 in Nepal. Thus, it is imperative to characterize the features of this disease in the domestic context. METHODOLOGY: We identified all adult patients with laboratory-confirmed COVID-19 admitted to five different hospitals in Nepal from June 15 to July 15, 2020. We collected epidemiological, socio-cultural and clinicopathologic data, and stratified the patients based on their symptom status. RESULTS: The study included 220 patients with an overall median age of 31.5 (25-37) years, and 181 (82.3%) were males. 159 (72.3%) were asymptomatic, and 163 (74.1%) were imported cases. Of 217 patients with the available data, 110 (50.7%) reported their annual household income less than 2000 US dollars, and 122 (56.2%) practiced Pranayama (yogic rhythmic breathing techniques) regularly. Eight patients (3.6%) required supplemental oxygen and two patients (0.9%) died. None of the patients who practiced Pranayama regularly required supplemental oxygen. Compared to asymptomatic patients, symptomatic patients had greater proportion of females (31.1% vs. 12.6%, p = 0.001), imported cases (85.2% vs. 69.8%, p = 0.02), illiterates (26.8% vs. 12.1%, p = 0.01), alcohol users (43.3% vs. 24.5%, p = 0.01), and had higher platelet count (253×109/L vs. 185×109/L, p = 0.02). CONCLUSIONS: Most cases were imported, asymptomatic young males, with very few deaths. Pranayama practice was associated with protection against severe COVID-19, but more data is needed to substantiate this. The association of platelets count with symptom status in the Nepalese population needs further exploration.

I(f) and SR Ca(2+) release both contribute to pacemaker activity in canine sinoatrial node cells.

Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a 'voltage clock' and a Ca(2+) dependent process, or 'Ca(2+) clock.' The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (I(f)) is thought to be particularly important. A Ca(2+) dependent process triggers APs when sarcoplasmic reticulum (SR) Ca(2+) release activates inward current carried by the forward mode of the electrogenic Na(+)/Ca(2+) exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca(2+) clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective I(f) antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest ( approximately 14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca(2+) release, but did not affect basal or isoproterenol-enhanced I(f). Taken together, these results indicate that voltage and Ca(2+) dependent automaticity mechanisms coexist in canine SAN cells, and suggest that I(f) and SR Ca(2+) release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells.

Knowledge and Attitude about COVID 19 among Health Care Workers Working in Seti Provincial Hospital.

BACKGROUND: Health care workers are at greater risk of infection during COVID 19 pandemic.  This study was carried out to assess the knowledge and attitude toward COVID-19 among healthcare workers at working at Seti Zonal Hospital. METHODS: A cross-sectional study was performed between April and May 2020 at Seti Zonal Hospital with purposive sampling technique and self-administered questionnaire of the knowledge and attitude of healthcare workers regarding COVID-19. The demographic characteristics mean knowledge and attitude score of healthcare workers were identified and inferential statistics t-test, ANOVA and Spearman's correlation were used to show the relationship between variables. RESULTS: A total of 230 healthcare workers (92% response rate) had a mean score of knowledge and attitude of 8±0.88 and 7.88±1.32, respectively with good knowledge and a low positive attitude. Majority (94.7%) were familiar with the sign and symptoms, agreed that chronic diseases patients and HCWs are at a higher risk (97%) and (87.8%) respectively while knowledge related to COVID 19 vaccination, isolation period and treatment by antibiotics was poor with low positive attitude towards information availability about COVID 19 (41%), government ability to control the epidemic (49%), and the family members might get infection (60%). There was a positive correlation between knowledge scores and attitude scores (r=0.28, p<0.0001). CONCLUSIONS: We identified a significant gap in information source, sufficient knowledge and low positive attitude about COVID 19 among health care workers. Greater educational efforts about prevention should be directed to different level of health workers.

MitraClip Implantation in a Patient With Post-Surgical Repair of Primum Atrial Septal Defect and Residual Mitral Cleft.

This paper presents the case of a 67-year-old female with primum atrial septal defect and congenital mitral cleft status-post surgical repair 40 years previously who was recently found to have severe mitral regurgitation. Percutaneous mitral valve repair was successfully performed using implantation of 2 MitraClips with mild residual mitral regurgitation. (Level of Difficulty: Advanced.).

Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT(2) receptor.

Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT(2) blocker PD-123319 (PD), or AT(1) blocker losartan, will affect this VT. Anesthetized dogs (n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1-3 h after CAO received AGII, and those with VT received either PD or losartan. Focal endocardium excised from ischemic sites was studied in vitro with standard microelectrode. Of 33 dogs with no inducible VT, AGII infusion resulted in sustained VT of only focal Purkinje origin in 13 (39%) compared with 0 of 20 dogs with saline. Of 26 dogs with inducible VT at baseline, given PD, reinduction was blocked in 8 of 10 (P < 0.05) focal VT, but only 1 of 15 with reentry. In contrast, of 11 dogs given losartan, reinduction of either mechanism was not blocked. In vitro triggered activity in Purkinje was blocked by PD in 13 of 19 (P < 0.05), but not by losartan in 8. Also, triggered activity was promoted by AGII, losartan, or the combination in 9 of 12 tissues. AGII promotes only focal, mainly Purkinje ischemic VT. PD, but not losartan, preferentially blocked focal VT, which is likely due to triggered activity due to delayed afterdepolarizations in Purkinje.