Massive haemorrhagic pericardial effusion as the cardiac manifestation of Salmonella enteritidis infection in a severely immunocompromised patient

A 41-years-old gentleman was admitted for reduced effort tolerance with non-specific symptoms of weight loss and generalised body weakness. Chest X-ray (CXR) showed cardiomegaly. Echocardiography showed a large pericardial effusion with septation. Emergency pericardiocentesis was performed and pericardial fluid culture grew Salmonella enteritidis (S. enteritidis). He tested positive for the retroviral disease, with a CD4 count of 10 cells/µL. Intravenous (IV) ceftriaxone was administered. A pericardial drain was inserted due to the rapid re-accumulation of pericardial fluid after the initial pericardiocentesis. He also had drainage of his left pleural effusion. He had a guidewire exchange of pericardial drain around 2 weeks after admission, with flushing performed whenever the flow was poor. A repeat echocardiogram showed early signs of constrictive pericarditis with residual pericardial effusion in which intrapericardial fibrinolysis was considered. He was started on antiretroviral therapy (ART) and his condition remained stable. The pericardial drain was kept throughout his admission. Unfortunately, he developed severe sepsis and succumbed to it about a month post-admission

Acute decompensated heart failure in a non cardiology tertiary referral centre, Sarawak General Hospital (SGH‑HF)

Abstract Background: Data on clinical characteristics of acute decompensated heart failure (ADHF) in Malaysia especially in East Malaysia is lacking. Methods: This is a prospective observational study in Sarawak General Hospital, Medical Department, from October 2017 to September 2018. Patients with primary admission diagnosis of ADHF were recruited and followed up for 90 days. Data on patient’s characteristics, precipitating factors, medications and short-term clinical outcomes were recorded. Results: Majority of the patients were classified in lower socioeconomic group and the mean age was 59 years old. Hypertension, diabetes mellitus and dyslipidaemia were the common underlying comorbidities. Heart failure with ischemic aetiology was the commonest ADHF admission precipitating factor. 48.6% of patients were having preserved ejection fraction HF and the median NT-ProBNP level was 4230 pg/mL. Prescription rate of the evidencebased heart failure medication was low. The in-patient mortality and the average length of hospital stay were 7.5% and 5 days respectively. 43% of patients required either ICU care or advanced cardiopulmonary support. The 30-day, 90-day mortality and readmission rate were 13.1%, 11.2%, 16.8% and 14% respectively. Conclusion: Comparing with the HF data from West and Asia Pacific, the short-term mortality and readmission rate were high among the ADHF patients in our study cohort. Maladaptation to evidence-based HF prescription and the higher prevalence of cardiovascular risk factors in younger patients were among the possible issues to be addressed to improve the HF outcome in regions with similar socioeconomic background. Keywords: Acute decompensated heart failure, Epidemiology, Sarawak, Southeast Asia, Malaysi

Clinical Outcome Predictor using Killip Scoring in Acute Decompensated Heart Failure (ADHF): A Non-Cardiac Centre Pilot Experience

Background: Physicians in tertiary centers face a constant challenge in selecting patient with ADHF to be admitted from district healthcare centre, especially with limited resources. Appropriate risk stratification of patients with ADHF would improve the efficiency of our healthcare delivery system. Objective: We aim to find potential relationship between Killip clinical scoring with clinical outcome of ADHF, including in-patient mortality and requirement of advanced cardiorespiratory support. Methods: 35 consecutive cases with a discharge diagnosis of ADHF and admission creatinine clearance of more than 30 were randomly reviewed. Cases were analyzed retrospectively for their Killip score, in-patient mortality, requirement of advance cardiorespiratory care or ICU admission. Results: There were 21 male patients (60%) and 14 female patients. Mean age was 61±19 years old. Mean duration of ward-stay was 6±4 days. Comorbidities were 14 (40%) with history of coronary artery diseases and 17 (49%) with diabetes mellitus. 15 patients (43%) were on at least a single type of guideline directed medication for heart failure. The cohort was almost evenly distributed between those with a Killip score of 2 and above 2. A Killip score of 3 and above was found to have good positive predictive value (87%) for advanced cardio-respiratory care and negative predictive value of 78%. No in-patient death was observed for the group with Killip 2 while 5 deaths were recorded in the group scoring more than 2. A Killip score of 3 had excellent (100%) negative predictive value for in-patient mortality but poor positive predictive value (33%). Significant relationship (p<0.001) was observed for Killip scoring on both outcomes. Conclusion: Killip scoring may be useful for on-call physician to decide the need on tertiary care among patient with ADHF and mortality outcome. However, more prospective studies and patients should be recruited to validate the study

COVID-19 Antibody Surveillance Among Healthcare Workers in A Non-COVID designated Cardiology Centre

BACKGROUND: Reports on healthcare worker antibody response to COVID-19 infection are scarce. We aim to determine theCOVID-19 antibody prevalence among healthcare workers in a cardiology centre and the relationship between case definitioncriteria with the COVID-19 antibody result. METHODS: Convenience sampling was applied. Healthcare workers in SarawakHeart Centre (SHC) cardiology, radiology, and emergency unit were recruited. A survey form on clinical symptoms and closecontact history was distributed. HEALGEN COVID-19 IgG/IgM rapid test was performed using serum/ whole blood specimen.Staff with positive COVID-19 antibody results were referred to the infectious disease specialist for assessment. RESULTS: Atotal of 310 staff were screened. 220(71%) were female, and the mean age was 36±7.7 years old. 46(14.8%) staff reported havingclinical symptoms at some stage from the end of January 2020 to the time of this surveillance. Number of staff who had a historyof overseas travel, close contact with confirmed COVID-19 patients, or had visited places with identified COVID-19 clusterswere 4(1.3%), 24(7.7%) and 24(7.7%) respectively. There were 14 staff (4.5%) with positive tests positive, 2 for IgM, and 12for IgG. All those with positive antibody were subsequently tested negative with RT-PCR test. The history of having clinicalsymptoms and exposure to COVID-19 cluster area were independently associated with a positive IgG result. CONCLUSION:The application of COVID-19 antibody serology rapid tests could determine true exposure of staff to the infection and allowus to reassess existing measures of infection control within the hospital

Clinical Outcomes and Predictors of Improved Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction due to Non-Ischemic Cardiomyopathy

Background: Left ventricular ejection fraction (LVEF) improvement is the cornerstone of LV reverse remodelling. It prognosticates heart failure with reduced ejection fraction (HFrEF). There is limited data on the clinical factors that predict LVEF improvement among non-ischemic cardiomyopathy (NICM) patients in Malaysia. Objective: To determine the 3-year outcomes and predictors of LVEF improvement in patients with (NICM) and HFrEF. Materials &amp; Methods: We recruited patients with NICM and HFrEF (LVEF &lt;40%) between 2016 and 2018. NICM was defined as HF with 1) normal coronary arteries or 2) any coronary artery stenosis not involving the proximal left anterior descending artery (LAD) and without transmural fibrosis in the LAD territory from cardiac magnetic resonance (CMR) imaging to account for the impaired LVEF. Clinical and imaging parameters were assessed using logistic regression statistics to determine the predictors of LVEF improvement. LVEF improvement is defined as a recovery of EF to &gt; 40% with at least a 10-point increment from baseline. The clinical outcomes at three year were 1) change in NYHA class and 2) composite of all-cause mortality, unscheduled clinic or emergency department visits, readmission and/or ventricular arrhythmia. Results: 43 patients were recruited. The mean duration of follow-up and echocardiographic assessment interval were 46 and 23 months, respectively. The cohort had a mean age of 46±13 years, and were mostly male (72%). More patients had NYHA 1 at the end of the study (37% vs 86%). 11 patients (25%) recorded composite outcomes. 62.8% had LVEF improvement. Patients with LVEF improvement had a lower incidence of late gadolinium enhancement (51.7% vs 85.7%, odds 5.6 ,p=0.045) and midwall fibrosis on CMR (18.5% vs 62.5%, odds 7.3, p=0.003). LVEF improvement did not affect the functional NYHA recovery (92% vs 81%, p=0.28). Patients with less LVEF improvement had higher incidence of composite outcome (18.5% vs 37.5%, p=0.168). Other characteristics were not significantly different between the groups. Conclusion: Patients with NICM and LVEF improvement had lower composite outcome. Absence of late gadolinium enhancement, particularly midwall fibrosis was an independant predictor of LVEF improvement. This underscores the importance of CMR tissue characterisation to refine the prognostication of NICM patients

Reversal of cardiac damage in patients with symptomatic severe aortic stenosis following transcatheter aortic valve implantation: An echocardiographic study

Background: Severe aortic stenosis (AS) results in cardiac damages, such as left ventricular hypertrophy, left atrial enlargement, pulmonary pressure elevation and in advanced stage, right ventricular damage. Généreux and colleagues proposed a staging classification based on these extra-valvular damages in 2017, with increasing stage representing more cardiac damage. While regression of these cardiac damages is expected following aortic valve replacement, the reversal of cardiac damage based on this staging system has not been described. Purpose: This study aimed to describe and stage the changes in cardiac structure and function at 6 months and 1 year after transcatheter aortic valve implantation (TAVI) in patients with symptomatic severe AS. Methods: This was a retrospective, single center, longitudinal observational study. Echocardiographic data of patients who underwent TAVI were retrieved and analysed. Results: From May 2018 to Feb 2021, 31 patients underwent TAVI. 5 patients were excluded due to death <6 months post-procedure (n=2) and incomplete echocardiographic data (n=3). The mean age of the remaining 26 patients was 70.9±9.4 years, 57.7% were male, and 34.6% bicuspid aortic valve. After TAVI, transvalvular aortic mean pressure gradient reduced from 45.2±14.5 mmHg to 8.0±5.4 mmHg (p<0.001), and aortic valve area increased from 0.57±0.21 cm2 to 1.75±0.68 cm2 (p<0.001). At baseline, 6-month and 1-year, the left ventricular mass index (LVMi) were 183.4±60.7g/m2, 150.8±55.3 g/m2 and 126.8±42.1 g/m2 (p<0.001) respectively; left-atrial volume index (LAVI) were 60.4±22.8 ml/m2 , 51.7±23.8ml/m2, and 48.1±23.6ml/m2 (p=0.009) respectively; left ventricular ejection fraction (LVEF) were 52.3±25.4%, 64.2±29.3%, and 62.4±12.1% (p=0.005) respectively. Based on the proposed cardiac damage staging for AS, at baseline 38% of patients were stage 1, 65.4% stage 2, 7.7% stage 3 and 23.1% stage 4. At 1 year, 8.3% were stage 0, 29.2% stage 1, 58.3% stage 2, and 4.2% stage 4. 12 patients (46%) showed improvement in cardiac damage staging, and the other 14 (54%) remained in the same stage. Conclusion: In patients with symptomatic severe AS, there were overall significant regression in LVMi and LAVI, and improvement in LVEF at 1 year after TAVI. However, improvement in cardiac damage staging was observed in only 46% of patients

Characterizing and Prognosticating Heart Failure with Improved Ejection Fraction Using NT-proBNP, Growth Differentiation Factor 15 and Global Longitudinal Strain

Background: Heart failure with improved ejection fraction (HFiEF) is a novel heart failure (HF) subgroup. There are sparse data on using NT-proBNP, growth differentiation factor 15 (GDF15) and global longitudinal strain (GLS) to characterize and prognosticate HFiEF patients. Objectives: (1) To determine the level and correlation between NT-proBNP, GDF-15 and GLS in HFiEF patients. (2) To examine the correlation of each marker with NYHA, MAGGIC prognostic score, HF etiologies, comorbidities status, degree of LVEF/ LV end-diastolic diameter change from baseline and diastolic dysfunction. (3) To look for association of each marker with follow-up LVEF change and 1-year composite mortality or HF events outcome. Materials & Methods: This was a cross-sectional observational study in Sarawak Heart Centre HF clinic. 53 HfiEF patients who had NT-proBNP and GDF15 tests performed were selected. This cohort had no HF events in the past 6 months during the blood tests. Clinical characteristics, echocardiography parameters, and 1-year composite clinical outcome were analyzed retrospectively. Results: The mean age of the cohort was 52 years old and 81% were male. The cohort was highly comorbid (hypertension 71%; diabetes 45.3%; AF 17.3%). Most of the patients (87%) were asymptomatic by NYHA (I) and low rate of composite outcome was observed, 5.7%. The mean NT-proBNP, GDF-15, GLS were 357 pg/ml, 1572 pg/ml, and -12.1% respectively. There were significant moderate correlation between GDF15 with NT-proBNP (r=0.414) and NT-proBNP with GLS (r=-0.351). Higher NT-proBNP and GDF15 levels were associated with poorer MAGGIC prognostic scores (r=0.549, 0.41 respectively). NT-proBNP was the only marker associated with a higher degree of LVEF improvement compare to baseline echocardiography. NT-proBNP was also related to severe diastolic echo parameters. Hypertension and diabetes were strongly associated with higher elevated GDF15 levels. The lower mean GLS level was significantly associated with the presence of composite outcome (-6.45% vs -12.47%, p=0.0). Patients with NT-proBNP levels below the median cutoff had favourable follow-up LVEF improvement (+9.73%, p=0.035). Conclusion: In our HFiEF study cohort, NT-proBNP best correlate and prognosticate future LV remodelling. GDF15 was closely related to systemic illnesses such as diabetes. The role of GLS in our HFiEF cohort remains uncertain

Local Ca2+ Entry Via Orai1 Regulates Plasma Membrane Recruitment of TRPC1 and Controls Cytosolic Ca2+ Signals Required for Specific Cell Functions

Store-operated Ca2+ entry (SOCE) has been associated with two types of channels: CRAC channels that require Orai1 and STIM1 and SOC channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC channels following Ca2+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct channels. We show that TRPC1/Orai1/STIM1-dependent ISOC, activated in response to Ca2+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated ICRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1(684EE685). In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and association of the channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca2+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 µM Gd3+, removal of extracellular Ca2+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca2+-containing, but not Ca2+-free, medium. Consistent with this, ICRAC is activated in cells pretreated with thapsigargin in Ca2+-free medium while ISOC is activated in cells pretreated in Ca2+-containing medium. Significantly, TRPC1 function is required for sustained KCa activity and contributes to NFκB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca2+ store depletion. We suggest that coordinated regulation of the surface expression of TRPC1 by Orai1 and gating by STIM1 provides a mechanism for rapidly modulating and maintaining SOCE-generated Ca2+ signals. By recruiting ion channels and other signaling pathways, Orai1 and STIM1 concertedly impact a variety of critical cell functions that are initiated by SOCE

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

TRP Channel Involvement in Salivary Glands—Some Good, Some Bad

Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Secretion of fluid by salivary glands is stimulated by activation of specific receptors on acinar cell plasma membrane and is mediated by an increase in cytosolic [Ca2+] ([Ca2+]i). The increase in [Ca2+]i regulates a number of ion channels and transporters that are required for establishing an osmotic gradient that drives water flow via aquaporin water channels in the apical membrane. The Store-Operated Ca2+ Entry (SOCE) mechanism, which is regulated in response to depletion of ER-Ca2+, determines the sustained [Ca2+]i increase required for prolonged fluid secretion. Core components of SOCE in salivary gland acinar cells are Orai1 and STIM1. In addition, TRPC1 is a major and non-redundant contributor to SOCE and fluid secretion in salivary gland acinar and ductal cells. Other TRP channels that contribute to salivary flow are TRPC3 and TRPV4, while presence of others, including TRPM8, TRPA1, TRPV1, and TRPV3, have been identified in the gland. Loss of salivary gland function leads to dry mouth conditions, or xerostomia, which is clinically seen in patients who have undergone radiation treatment for head-and-neck cancers, and those with the autoimmune exocrinopathy, Sj&ouml;gren&rsquo;s syndrome (pSS). TRPM2 is a unique TRP channel that acts as a sensor for intracellular ROS. We will discuss recent studies reported by us that demonstrate a key role for TRPM2 in radiation-induced salivary gland dysfunction. Further, there is increasing evidence that TRPM2 might be involved in inflammatory processes. These interesting findings point to the possible involvement of TRPM2 in Sj&ouml;gren&rsquo;s Syndrome, although further studies will be required to identify the exact role of TRPM2 in this disease