Coronary atherosclerosis among symptomatic patients with zero coronary artery calcium score in computed tomography coronary angiography.

BACKGROUND: Computed tomographic coronary angiography has been recognized as a reliable imaging modality with excellent negative predictive value and a good negative likelihood ratio to exclude coronary artery disease in stable, symptomatic patients with intermediate or high risk. 1) Coronary calcium scoring has been extensively shown to be an invaluable tool to exclude the presence of coronary artery disease in low-risk patients. 2) Our aim was to identify the presence and extent of coronary atherosclerosis in computed tomographic coronary angiography in stable symptomatic patients with a zero Coronary Calcium score. RESULTS: Three hundred and eighty-three (383) consecutive patients aged ≥ 18 years fulfilling the criteria were enrolled as of January 1, 2021; 165 (43.1%) were male and 218 (56.9%) were female, with a mean age of 57.8 ± 4.9 years and a zero coronary artery calcium score. Two hundred and twenty-six (226) (59.0%) were hypertensive, followed by 125 (32.6%) who were smokers, and 117 (30.5%) who were diabetic. The frequency of atherosclerotic plaque in coronary arteries was 34 (8.9%), with 16 (47.1%) being male and 18 (52.9%) being female. The mean age of patients with atherosclerosis was 54.9 ± 3.3 years; among them, 13 (38.2%) were between the ages of 45 and 54, and 10 (29.4%) were between the ages of 55 and 64. Nineteen (19) (55.9%) were hypertensive, followed by 10 (29.4%) with dyslipidemia. Twenty-three (23) (67.6%) had non-obstructive plaque, and 11 (32.3%) had obstructive plaque. In the subgroup of patients with non-obstructive plaque, 13 (56.5%) were hypertensive, 8 (34.8%) were diabetic, and 16 (69.6%) had single vessel disease, while among patients with obstructive plaque, 6 (54.5%) were hypertensive, 5 (45.5%) were smokers, and all of them had single vessel disease. The most affected artery was the left anterior descending artery. CONCLUSION: As the frequency of atherosclerotic plaque in patients with a zero coronary calcium score is relatively high, computed tomographic coronary angiography is indicated in stable, symptomatic patients with a lower likelihood of coronary artery disease.

Use of Statin and Target Low-density lipoprotein cholesterol attainment among post-ST elevation myocardial infarction patients in Shahid Gangalal National Heart Centre, Kathmandu, Nepal.

BACKGROUND: and objective: Lipid-lowering is an important intervention to reduce cardiovascular morbidity and mortality in the secondary prevention of STEMI. There is no study to analyze the use of statin and LDL-C treatment target attainment among STEMI patients in Nepal. This study aims to assess the use of statin and LDL-C treatment target attainment among STEMI patients. METHODS: It was a prospective observational single-center study conducted at the Shahid Gangalal National Heart Centre, Kathmandu, Nepal outpatient department. An outpatient department-based survey was conducted among STEMI patients who have lipid profile levels at the time of admission for STEMI and after 4-13 weeks of the index event. Lipid profile levels, diagnosis, and risk factors were collected during the outpatient follow-up. RESULTS: Our study included 280 post-STEMI patients; the mean age was 57.5±11.7 years with the majority being male. The mean duration of follow-up was 6.7 ± 0.1 weeks. Rosuvastatin was the preferred statin with 82.1%. The most common dose of statin used was Rosuvastatin 20mg (70%), followed by Atorvastatin 40mg (12.5%). LDL-C levels of <1.4mmol/l were achieved in 44.6% of cases and LDL levels of <1.8mmol/l in 71.8% of cases. In 36.8% of the study population, there was a greater than 50% decline in LDL-C levels. Diabetic patients (55.1% and 83.1%) only have the significant achievement of LDL goal of both <1.4mmol/l and <1.8mmol/l respectively, when compared to those without diabetes (44.9% and 16.9%). CONCLUSIONS: Most of the post-STEMI patients were treated with high doses of statins and achieved the target LDL-C levels.

Prevalence and Comparision of Conventional Risk Factors of Cardiovascular Disease Between Clinical and Nonclinical Staff.

BACKGROUND: Cardiovascular disease is the leading cause of death around the globe. A number of studies have shown that hospital staff are vulnerable to cardiovascular disease due to a certain risk of shift duty. It is important to identify cardiovascular risk factors among hospital staff. The aim of this study is, to assess the prevalence of conventional risk factors of cardiovascular disease among hospital staff. METHODS: A quantitative cross-sectional study was conducted among staff working at a Shahid Gangalal National Heart Center, a tertiary cardiac center in Nepal. Simple and multiple linear regression analyses were used to examine the association between independent variables and cardiovascular diseases. Statistical analysis was done using SPSS software version 20. RESULTS: A total of 250 hospital staff participated in this study. Among them, 137 were clinical staff and 113 were non-clinical staff. The mean age of clinical staff and the non-clinical staff was 33.69 ± 7.02 years and 38.7 ± 10.58 years respectively with a total of 66.8% females. Prevalence of hypertension, diabetes mellitus, and dyslipidaemia was less in clinical staff compared to non-clinical staff. The mean systolic, diastolic BP was high in non-clinical staff ( P-value 0.001), moreover mean HDL-C was low (1.2 ± 0.2 mmol). BMI was significantly low in clinical staff. [standardized ß= -0.24; 95% CI: -2.90, -0.88]. CONCLUSIONS: The prevalence of cardiovascular risk factors were high in non-clinical staff compared to clinical staff.

Patterns of Perception of Cardiac Symptoms by Patients Presenting with ST-Segment Elevation Myocardial Infarction and their Knowledge of Coronay Artery Disease Risk Factors.

BACKGROUND: Proper knowledge regarding Coronary Artery Disease and their risk factors is essential for the early recognition of the disease and its presentation. This study was conducted to identify pattern of clinical symptoms and knowledge regarding Coronary Artery Disease risk factors among ST-Elevation myocardial infarction (STEMI) patients. METHODS: This cross-sectional, observational study was conducted among 340 ST-Elevation myocardial infarction patients in the inpatient Cardiology Department of Shahid Gangalal National Heart Centre Nepal, from November 2020 to February 2021. Baseline clinical characteristics, knowledge regarding Coronary Artery Disease risk factors, patterns of symptoms, and prehospital delay were collected and evaluated. RESULTS: In our study, 299 (87.9%) had typical ischemic chest pain during the symptom onset, however, only 81 (23.8%) perceived chest pain as cardiac disease, and 311 (91.5%) of the patients presented to the nearby health care center within the recommended time of less than 12 hours for the reperfusion therapy of ST-Elevation myocardial infarction. Perception of symptoms as a cardiac origin and typical chest pain were not significantly associated with earlier presentation. Also, the typical chest pain was not significantly associated with the perception of the symptom as a cardiac origin. The history of Coronary Artery Disease was considered as a Coronary Artery Disease risk factor by 184(54.1%) of the study population and 137(40.3%), 132(38.8%), 110(32.4%), 105(30.9%) and 71(20.9%) considered hypertension, smoking, age, obesity, and diabetes mellitus as a Coronary Artery Disease risk factor respectively. CONCLUSIONS: Though most patients presented with typical chest pain, identification of the chest pain as a cardiac origin and the awareness of the Coronary Artery Disease risk factors was low.

Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome.

The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae-dominated microbiomes than in Bacteroidaceae-dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline. Together, these data provide insight into the relevance of native gut microbiota signatures, dietary intake and systemic inflammation in shaping the response to and toxicity from ICIs, prompting the need for further studies in this area.

Comprehensive Clinical, Histopathologic, and Molecular Analysis and Long-term Follow-up of Patients With Nodal Blue Nevi.

Blue nevi are benign, melanocytic neoplasms that show a range of clinical and morphologic patterns and include common/dendritic, cellular, and atypical cellular subtypes. Like other nevi, they most commonly occur in skin but can occasionally involve lymph nodes where they may be misinterpreted as representing metastatic melanoma. Moreover, whether benign blue nevi can metastasize to lymph nodes and their natural history and prognostic significance has been the subject of great controversy. To date, few cases of nodal blue nevi have been reported in the literature, and those reports have had limited clinical follow-up and supporting molecular data. This study sought to determine the clinical, pathologic, and molecular features of blue nevi involving lymph nodes, clarify their clinical significance, provide evidence for understanding their pathogenesis, and highlight potential pitfalls in the interpretation of lymph nodes with an ultimate aim of improving patient care. Thirteen cases of blue nevi involving lymph nodes were identified in the archives of Royal Prince Alfred Hospital, Sydney, Australia (1984-2018). A detailed assessment of the clinical and pathologic features of each case was performed, including an evaluation of all available immunohistochemical stains. Extended clinical follow-up was available for 9 patients. Droplet digital polymerase chain reaction for GNAQ Q209L, Q209P and GNA11 Q209L mutations was performed on 7 cases of blue nevi within lymph nodes together with matching cutaneous (presumed primary) blue nevi in 2 cases. All cases showed typical histologic features of blue nevi. BAP1 was retained in all cases (n=7). There were no recurrence or metastasis of blue nevus in any case on long-term clinical follow-up (n=9, median follow-up, 12 y). The majority of cases (n=5 of 7 evaluated) had GNAQ and GNA11 driver mutations. The 2 patients with a matched primary cutaneous blue nevus and regionally associated nodal blue nevus had the same GNAQ Q209L mutation in both sites in each patient. We conclude that blue nevi can involve lymph nodes and are associated with benign clinical behavior, and probably represent so-called "benign" metastasis. Awareness of these lesions is important when evaluating lymph nodes to avoid misdiagnosis as metastatic melanoma.

Safety and Efficacy of Single vs Dual Antiplatelets Therapy After Atrial Septal Defect Device Closure.

BACKGROUND: Atrial septal defect device closure has become a standard procedure. Antiplatelet therapy is used to prevent thrombus formation in the device. There is no clear recommendation about the antiplatelets drugs. This study aims to evaluate the safety and efficacy of Aspirin vs (Aspirin +Clopidogrel) after device closure. METHODS: A cross-sectional study was conducted among all consecutive adult patients (?18 years) who underwent atrial septal defect device closure from May 2019 to April 2020 and meet the inclusion criteria were included. After successful ASD device closure patients were treated with ASA or combination of ASA and Clopidogrel for six months on physician discretion. Patients were followed up for six months to observe for Transient ischemic attack, Stroke, thrombus in the device, myocardial infarction, major bleeding, minor bleeding and increases in headache episodes compared to baseline. RESULTS: This study consisted of 130 patients: 65 in the Aspirin Group, and 65 patients in Aspirin and Clopidogrel group. There was no Transient ischemic attack, Stroke, Myocardial infarction, thrombus, major bleeding in both groups. There was no significant difference between two groups in ecchymosis; Aspirin group 4(6.1%) vs. aspirin and Clopidogrel group 3(4.6%) [Difference, 1.54% {95, % CI, -1.45%to 4.53%}]; P=0.648. There was no significant difference in increase in headache episodes compared to baseline for six months after the device closure in Aspirin Group 3(4.6%) VS Aspirin and Clopidogrel group 2 (3.0%) group [difference, 1.54% {95% CI, -1.45%to 4.53%}]; P=0.648. CONCLUSIONS: Our study suggests that single antiplatelet therapy with Aspirin is as safe and effective as aspirin and clopidogrel after device closure.

In Hospital Complications of Atrial Septal Defect Device Closure at Shahid Gangalal National Heart Centre, Kathmandu, Nepal.

BACKGROUND: Atrial deptal defect device closure has become the preferred method in the treatment of atrial septal defect. We aim to study the in-hospital complications of atrial septal defect device closure procedure. METHODS: It was a single center, retrospective study conducted from Febuary 2016 to January 2019. Cardiac catheterization laboratory records of all consecutive patients who underwent atrial septal defect device closure was included and the in-hospital complications were been retrospectively reviewed. RESULTS: During the study period, a total of 566 patients were attempted for device closure. In 557 (98.4%) of cases device was implanted. Among the 557 patient in which device was implanted 401(71.9%) were female. Age ranged from 5 years to 72 years with the mean of 30.9 years. Transient ST segment elevation 15 (2.6 %)was the commonest complication followed by pericardial tamponade 4 (0.7%), and cardiac arrhythmias 3 (0.5%). CONCLUSIONS: Atrial deptal defect device closure can be done safely with a high success rate and a low complication rate.

Atrial Septal Defect Size and Rims on Transesophageal Echocardiogram.

Background and aims:Rims and size of atrial septal defect (ASD) are crucial for the success of transcatheter ASD closure. The maximal diameter and dimensions of various rims of the ASD are essential for sizing and optimal placement of the device. We aimed to study the size and rims of ASD in our patients. Methods:This was a prospective study that was done at Shahid Gangalal National Heart Centre. All patients aged over 18 and referred to a unit IV in the Department of Cardiology for ASD device closure were included in the study. The study duration was six months, from April to September 2018. The size and rims of ASD were evaluated by transesophageal echocardiogram. Results:During the study, 173 patients underwent transesophageal echocardiogram. Most of them [122 (70.1%)] were women. Age ranged from 18 to 68 (mean, 35 years). The most common symptom was shortness of breath. Twenty-one (12.1%) patients were incidentally detected with ASDs. Sinus rhythm with right bundle branch block was present in 148 (85.5%) subjects. Right atrium and right ventricle were dilated in 162 (93.6%) patients. One patient had dextrocardia with situs inversus. More than half of all patients (54.9%) had mild tricuspid regurgitation. Mean tricuspid regurgitation pressure gradient was 39.5±16.8 mm Hg. More than one ASD was present in 11 (6.3%) patients. ASD size ranged from 2 mm to 43 mm in 4-chamber view, 2 mm to 44 mm in short axis view, and 2 mm to 47 mm in bicaval view. The mean ASD size was 18.6±7.7 mm in 4-chamber view, 19.6±8.5 mm in short axis view, and 18.7±8.0 mm in bicaval view. In only 11 (6.4%) patients, all rims were present and not floppy, while in other 11 (6.4%) subjects all rims were present, but floppy. With the exception of aortic rim, all other rims were present and good in 55 (33.9%) patients, while in 45 (27.7%) patients, other rims were present but floppy. Conclusion:Many ASD have absent, inadequate and floppy rims.

Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial.

BACKGROUND: The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials, and no patients with a pathological response have relapsed after a median follow up of 32 months. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo trial was to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective. METHODS: OpACIN-neo is a multicentre, open-label, phase 2, randomised, controlled trial. Eligible patients were aged at least 18 years, had a WHO performance status of 0-1, had resectable stage III melanoma involving lymph nodes only, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients were enrolled from three medical centres in Australia, Sweden, and the Netherlands, and were randomly assigned (1:1:1), stratified by site, to one of three neoadjuvant dosing schedules: group A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks intravenously; group B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks intravenously; or group C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3 mg/kg once every 2 weeks intravenously. The investigators, site staff, and patients were aware of the treatment assignment during the study participation. Pathologists were masked to treatment allocation and all other data. The primary endpoints were the proportion of patients with grade 3-4 immune-related toxicity within the first 12 weeks and the proportion of patients achieving a radiological objective response and pathological response at 6 weeks. Analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02977052, and is ongoing with an additional extension cohort and to complete survival analysis. FINDINGS: Between Nov 24, 2016 and June 28, 2018, 105 patients were screened for eligibility, of whom 89 (85%) eligible patients were enrolled and randomly assigned to one of the three groups. Three patients were excluded after randomisation because they were found to be ineligible, and 86 received at least one dose of study drug; 30 patients in group A, 30 in group B, and 26 in group C (accrual to this group was closed early upon advice of the Data Safety Monitoring Board on June 4, 2018 because of severe adverse events). Within the first 12 weeks, grade 3-4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. The difference in grade 3-4 toxicity between group B and A was -20% (95% CI -46 to 6; p=0·158) and between group C and group A was 10% (-20 to 40; p=0·591). The most common grade 3-4 adverse events were elevated liver enzymes in group A (six [20%)]) and colitis in group C (five [19%]); in group B, none of the grade 3-4 adverse events were seen in more than one patient. One patient (in group A) died 9·5 months after the start of treatment due to the consequences of late-onset immune-related encephalitis, which was possibly treatment-related. 19 (63% [95% CI 44-80]) of 30 patients in group A, 17 (57% [37-75]) of 30 in group B, and nine (35% [17-56]) of 26 in group C achieved a radiological objective response, while pathological responses occurred in 24 (80% [61-92]) patients in group A, 23 (77% [58-90]) in group B, and 17 (65% [44-83]) in group C. INTERPRETATION: OpACIN-neo identified a tolerable neoadjuvant dosing schedule (group B: two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg) that induces a pathological response in a high proportion of patients and might be suitable for broader clinical use. When more mature data confirm these early observations, this schedule should be tested in randomised phase 3 studies versus adjuvant therapies, which are the current standard-of-care systemic therapy for patients with stage III melanoma. FUNDING: Bristol-Myers Squibb.

A 12-Year Retrospective Study of Invasive Amoebiasis in Western Sydney: Evidence of Local Acquisition.

In Australia, amoebiasis is thought to occur in travellers, immigrants from endemic areas, and among men who have sex with men. Prevalence of amoebiasis in communities with immigrants from Entamoeba histolytica-endemic countries is unknown. The present study is a retrospective case series analysis of patients with laboratory-confirmed amoebiasis from Western Sydney Local Health District, Australia, between years 2005 and 2016. Forty-nine patients with amoebiasis were identified, resulting in an estimated annual incidence of up to 1.1 cases per 100,000 adults. Many were born in Australia (15/47) and India (12/47). Three patients (3/37) had no history of overseas travel, two others had not travelled to an endemic country, and an additional two had a very remote history of overseas travel; one died of fulminant amoebic colitis. Three patients (3/16) were employed in the food industry and one had a history of colonic irrigation in an Australian 'wellness clinic'. Patients had invasive amoebiasis with either liver abscess (41/48) or colitis (7/48), diagnosed most commonly by serology. Invasive procedures were common, including aspiration of liver abscess (28/41), colonoscopy (11/49), and partial hepatectomy (1/49). Although rare, local acquisition of amoebiasis occurs in Western Sydney and contributes to significant morbidity and hospital admissions.

Percutaneous transluminal mitral valvuloplasty in post Mitral valve repair and Aortic valve replacement patient.

MV repair in the rheumatic population is feasible with acceptable long-term results. Incidence of mitral stenosis (MS) following mitral valve (MV) repair for severe rheumatic mitral regurgitation (MR) and usefulness of percutaneous transluminal mitral valvuloplasty in these patients is not described in literature. We report a case of successful PTMC in severe MS following MV repair for severe rheumatic MR.