Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Artificial Intelligence-Assisted Detection of Osteoporotic Vertebral Fractures on Lateral Chest Radiographs in Post-Menopausal Women.

Osteoporotic vertebral fractures (OVFs) are often not reported by radiologists on routine chest radiographs. This study aims to investigate the clinical value of a newly developed artificial intelligence (AI) tool, Ofeye 1.0, for automated detection of OVFs on lateral chest radiographs in post-menopausal women (>60 years) who were referred to undergo chest x-rays for other reasons. A total of 510 de-identified lateral chest radiographs from three clinical sites were retrieved and analysed using the Ofeye 1.0 tool. These images were then reviewed by a consultant radiologist with findings serving as the reference standard for determining the diagnostic performance of the AI tool for the detection of OVFs. Of all the original radiologist reports, missed OVFs were found in 28.8% of images but were detected using the AI tool. The AI tool demonstrated high specificity of 92.8% (95% CI: 89.6, 95.2%), moderate accuracy of 80.3% (95% CI: 76.3, 80.4%), positive predictive value (PPV) of 73.7% (95% CI: 65.2, 80.8%), and negative predictive value (NPV) of 81.5% (95% CI: 79, 83.8%), but low sensitivity of 49% (95% CI: 40.7, 57.3%). The AI tool showed improved sensitivity compared with the original radiologist reports, which was 20.8% (95% CI: 14.5, 28.4). The new AI tool can be used as a complementary tool in routine diagnostic reports for the reduction in missed OVFs in elderly women.

Comparison of coronary artery calcium score and cardiovascular risk-stratification by European Society of Cardiology Guidelines and Steno Type 1 Risk Engine in statin-naïve adults with type 1 diabetes.

BACKGROUND: Coronary artery calcium (CAC) is a marker of atherosclerotic cardiovascular disease (CVD). However, for patients with type 1 diabetes (T1D), its relationship with T1D-specific cardiovascular (CV) risk-stratification tools is unknown. AIMS: Assess prevalence of CAC and evaluate relationship between CAC and T1D-specific CV risk-stratification methods in T1D. METHODS: Cross-sectional study of adults with T1D age 20-60 years, statin-naïve and no history of CVD. Data was obtained from electronic medical records and by interview. Presence of CAC was assessed using non-contrast cardiac computed tomography and quantified by Agatston Units (AU). CV risk-stratification was assessed using the 2019 European Society of Cardiology (ESC) Guidelines and the Steno T1 Risk Engine (ST1RE). RESULTS: 85 patients were included with mean age 35.4 ± 10.3 years, HbA1c 8.3 ± 1.5 % and T1D duration 17.0 ± 10.1 years. 67 patients (78.9 %) had a CAC score of 0 AU, 17 (20.0 %) >0-100 AU, and one (1.2 %) >100 AU. Duration of T1D (p = 0.009), body mass index (p = 0.029), neuropathy (p = 0.016) and low-density lipoprotein cholesterol levels (p = 0.016) were independently associated with a positive CAC score on multivariate analysis. Positive predictive value for a positive CAC score was 85.7 % for the ST1RE high risk category and 31.3 % for the 2019 ESC Guidelines very high risk category. CONCLUSIONS: One-fifth of this T1D cohort had a positive CAC score. The ST1RE was superior in identifying positive CAC compared to the 2019 ESC Guidelines. Further studies are required to elucidate the role of CAC in personalising CV risk-stratification and statin initiation in T1D.

2-Oxindole and related heterocycles: synthetic methodologies for their natural products and related derivatives.

Natural goods, medications, and pharmaceutically active substances all contain substituted oxindoles. Generally, the C-3 stereocenter of the substituents of oxindoles and their absolute arrangement have a substantial impact on the bioactivity of these substances. In this case, the desire for contemporary probe and drug-discovery programs for the synthesis of chiral compounds using desirable scaffolds with high structural diversity further drives research in this field. Also, the new synthetic techniques are generally simple to apply for the synthesis of other similar scaffolds. Herein, we review the distinct approaches for the synthesis of diverse useful oxindole scaffolds. Specifically, the research findings on the naturally existing 2-oxindole core and a variety of synthetic compounds having a 2-oxindole core are discussed. We present an overview of the construction of oxindole-based synthetic and natural products. In addition, the chemical reactivity of 2-oxindole and its related derivatives in the presence of chiral and achiral catalysts are thoroughly discussed. The data compiled herein provides broad information related to the bioactive product design, development, and applications of 2-oxindoles and the reported techniques will be helpful for the investigation of novel reactions in the future.

Clinical characteristics, etiological profile, treatment and long term outcomes in patients with non ischemic systolic heart failure; Himachal Pradesh heart failure registry (HP-HF registry).

BACKGROUND: The data on clinical characteristics, treatment practices and out comes in patients with Non- ischemic Systolic Heart Failure (NISHF) is limited. We report clinical characteristics, treatment and outcomes in patients with NISHF. METHODS: 1004 patients with NISHF were prospectively enrolled and their demographics, clinical characteristics, and treatment were recorded systematically. Patients were followed annually for a median of 3 years (1 year to 8 years) for allcause death, major adverse cardiovascular events (MACE); composite of all-cause death, hospitalization of heart failure, and or for stroke. RESULTS: Patients of NISHF were middle-aged (58.8±16.2 years) population with severely depressed left ventricular ejection fraction (29.3±7.02%) and 31.1% had symptoms of advanced Heart failure. Hypertension (43.6%), obesity and or overweight (28.0%), Diabetes (15.0%), and valvular heart disease (11.8%) were the common risk factors. The guideline directed medical treatment was prescribed in more than 80% of the study cohort. Incidence of all cause death and MACE was 7 (6.8, 8.8) per 100 person years and 11(10, 13) per 100 person years respectively. The cumulative incidence of deaths and MACE was 35% (30%, 40%) and 49% (44%, 53%) at 8 years of follow-up. CONCLUSIONS: Patients of NISHF were middle-aged population with severely depressed LV systolic function with significant incident morbidity and mortality. Early detection of risk factors and their risk management and enhancing the use of guideline directed treatment may improve the outcomes.

Investigation of the Relationship between Right Coronary Artery-Aorta Angle and Coronary Artery Disease and Associated Risk Factors.

At the level of the left coronary artery tree, there is evidence showing an association between bifurcation angle and coronary artery disease (CAD), and this motivated us to explore similar associations at the level of the right coronary artery (RCA). The purpose of this study was to determine whether there is a relationship between RCA-aorta angle and CAD and age, sex, body mass index, smoking status, hypertension, and high blood cholesterol. The coronary computed tomography angiography datasets and CAD risk factor checklists of 250 patients were retrospectively reviewed, with RCA-aorta angles measured via multiplanar reformation images. Independent t-tests were used to compare mean RCA-aorta angle measurements between groups, correlations between continuous variables were assessed using Pearson and Spearman correlations, and a general linear model was used to adjust for potentially confounding variables. Coronary angle measurements were conducted by two independent assessors with very strong intraclass correlation (r=0.999, p<0.001). A significantly smaller mean RCA-aorta angle was observed in the CAD group (79.07 ± 24.88°) compared to the normal group (92.08 ± 19.51°, p=0.001), in smokers (76.63 ± 22.94°) compared to non-smokers (85.25 ± 23.84°, p=0.016), and a narrow RCA-aorta angle was negatively correlated with BMI (r=-0.174, p=0.010). This study suggests a relationship between narrow RCA-aorta angles and CAD, smoking, and increasing BMI.

Incidence, determinants, and outcomes of recovered left ventricular ejection fraction (LVEF) in patients with non-ischemic systolic heart failure; a hospital-based cohort study.

BACKGROUND: The data on incidence of recovered Left Ventricular Ejection Fraction (LVEF) and outcome in patients with non ischemic systolic heart failure is limited. We report the incidence, determinants and mortality in patients with recovered LVEF. METHODS: The 369 patients with HFrEF with LVEF of less than 40% of non ischemic etiology with available follow up echocardiography study at one year were enrolled. The baseline data of clinical characteristics and treatment was recorded prospectively and were followed up annually for mean of 3.6 years (range 2 to 5 years) to record all cause death and LVEF measured echocardiographically. The recovered, partially recovered and no recovery of LVEF was defined based on increase in LVEF to 50% and more, 41% to 49% and to persistently depressed LVEF to 40% or lower respectively. RESULTS: The LVEF recovered in 36.5%% of the cohort at 5 years. The rate of recovery of LVEF was slower in patients with no recovery of LVEF at one year compared to cohort with partially recovered LVEF (18% vs.53%) at five year. The Baseline LVEF was significantly associated with recovered LVEF, odd ratio (95% C.I.) 1.09(1.04, 1.14). The cumulative mortality at five years was significantly lower in cohort with recovered LVEF (18.1% vs. 57.1%). CONCLUSIONS: One third of the patients had recovered LVEF and was significantly associated with baseline LVEF and lower mortality rate.

Clinical Applications of Mixed Reality and 3D Printing in Congenital Heart Disease.

Understanding the anatomical features and generation of realistic three-dimensional (3D) visualization of congenital heart disease (CHD) is always challenging due to the complexity and wide spectrum of CHD. Emerging technologies, including 3D printing and mixed reality (MR), have the potential to overcome these limitations based on 2D and 3D reconstructions of the standard DICOM (Digital Imaging and Communications in Medicine) images. However, very little research has been conducted with regard to the clinical value of these two novel technologies in CHD. This study aims to investigate the usefulness and clinical value of MR and 3D printing in assisting diagnosis, medical education, pre-operative planning, and intraoperative guidance of CHD surgeries through evaluations from a group of cardiac specialists and physicians. Two cardiac computed tomography angiography scans that demonstrate CHD of different complexities (atrial septal defect and double outlet right ventricle) were selected and converted into 3D-printed heart models (3DPHM) and MR models. Thirty-four cardiac specialists and physicians were recruited. The results showed that the MR models were ranked as the best modality amongst the three, and were significantly better than DICOM images in demonstrating complex CHD lesions (mean difference (MD) = 0.76, p = 0.01), in enhancing depth perception (MD = 1.09, p = 0.00), in portraying spatial relationship between cardiac structures (MD = 1.15, p = 0.00), as a learning tool of the pathology (MD = 0.91, p = 0.00), and in facilitating pre-operative planning (MD = 0.87, p = 0.02). The 3DPHM were ranked as the best modality and significantly better than DICOM images in facilitating communication with patients (MD = 0.99, p = 0.00). In conclusion, both MR models and 3DPHM have their own strengths in different aspects, and they are superior to standard DICOM images in the visualization and management of CHD.

Enhanced Visualisation of Normal Anatomy with Potential Use of Augmented Reality Superimposed on Three-Dimensional Printed Models.

Anatomical knowledge underpins the practice of many healthcare professions. While cadaveric specimens are generally used to demonstrate realistic anatomy, high cost, ethical considerations and limited accessibility can often impede their suitability for use as teaching tools. This study aimed to develop an alternative to traditional teaching methods; a novel teaching tool using augmented reality (AR) and three-dimensional (3D) printed models to accurately demonstrate normal ankle and foot anatomy. An open-source software (3D Slicer) was used to segment a high-resolution magnetic resonance imaging (MRI) dataset of a healthy volunteer ankle and produce virtual bone and musculature objects. Bone and musculature were segmented using seed-planting and interpolation functions, respectively. Virtual models were imported into Unity 3D, which was used to develop user interface and achieve interactability prior to export to the Microsoft HoloLens 2. Three life-size models of bony anatomy were printed in yellow polylactic acid and thermoplastic polyurethane, with another model printed in white Visijet SL Flex with a supporting base attached to its plantar aspect. Interactive user interface with functional toggle switches was developed. Object recognition did not function as intended, with adequate tracking and AR superimposition not achieved. The models accurately demonstrate bony foot and ankle anatomy in relation to the associated musculature. Although segmentation outcomes were sufficient, the process was highly time consuming, with effective object recognition tools relatively inaccessible. This may limit the reproducibility of augmented reality learning tools on a larger scale. Research is required to determine the extent to which this tool accurately demonstrates anatomy and ascertain whether use of this tool improves learning outcomes and is effective for teaching anatomy.

Discovery of MDV6058 (PF-06952229), a selective and potent TGFßR1 inhibitor: Design, synthesis and optimization.

Compound 1 is a potent TGF-ß receptor type-1 (TGFßR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.

Recommended clinical practice guidelines of aesthetic dentistry for Indians: An expert consensus.

Objective: The research for analyzing the smile characteristics in the Indian population has been limited with contradictory outcomes. This consensus statement aims to critically review the literature and provide basic practice guidelines on dental aesthetics related to the Indian population. Clinical Considerations: 9 clinicians and 6 resource persons from dental colleges in India collaborated in this consensus statement which covered 6 topics along with 6 introductory and 6 conclusive remarks. The statement was developed through a colloquium conducted on topics; global aesthetics: different smile design proportions and guidelines, patient perspective towards aesthetic dentistry in India, a literature survey of aesthetic dentistry for the Indian population, macro and micro-aesthetics, multidisciplinary approach in aesthetic dentistry, inclusion of high-end technologies in Indian modern-day practice, followed by a panel discussion to devise and establish the practice guidelines of aesthetic dentistry in India. The Consensus Statement has been formulated according to AGREE Reporting checklist. Conclusion: The experts and panelists reached a Consensus on protocols to institute clinical practice guidelines of aesthetic dentistry for Indians. However, based on all available literature from India, further research is required to investigate many questions that have not been previously considered.

Transient left ventricular dysfunction after therapeutic pericardiocentesis - Takotsubo cardiomyopathy or pericardial decompression syndrome.

We present a case of reversible left ventricular (LV) dysfunction with characteristic stress or "Takotsubo" cardiomyopathy (SCM) after therapeutic pericardiocentesis in a patient with tubercular pericardial effusion. SCM following pericardiocentesis is uncommon, as opposed to the well-defined entity, pericardial decompression syndrome (PDS). PDS is defined as a paradoxical deterioration of hemodynamics and development of severe biventricular dysfunction, cardiogenic shock, and pulmonary edema after uneventful, often large volume pericardiocentesis in patients of pericardial effusion.

Coronary computed tomographic angiography derived findings and risk score improves the allocation of lipid lowering therapy compared to clinical score.

ABSTRACT: The initiation of therapy for atherosclerotic cardiovascular disease (ASVCD) is currently guided by cohort-based risk scores. Coronary computed tomographic angiography (CCTA) offers more personalised risk assessments to optimise therapy allocation. This study investigates the utility of CCTA determined coronary stenosis (both obstructive and non-obstructive plaque) to guide allocation of lipid lowering therapy. A retrospective analysis of 450 patients with CCTA performed for the assessment of chest pain at a single centre was conducted. Baseline characteristics, investigations, treatments and clinical outcomes were recorded. The allocation of lipid lowering therapy was evaluated with three models, cohort-based risk score (pooled cohort equation), a previously validated CCTA based clinical risk score (pooled cohort equation and CCTA findings) and CCTA alone (without clinical characteristics). The reclassification analysis included 266 patients. Compared to the cohort-based risk score, CCTA based clinical risk score in total reassigned 23% of patients. CCTA alone compared to the CCTA based clinical risk score correctly reassigned 23% and incorrectly reassigned 10%. When comparing the performance of CCTA alone against the cohort-based risk score, both the additive NRI of 25.8 (95% CI 4.12-37.56) and absolute NRI of 13.2 (95% CI 5.88-19.77) was significant. Revascularisation was required in 3% with a low cohort-based risk, but no patients with low risk as per CCTA alone or CCTA based clinical risk score required revascularisation The use of a CCTA based clinical risk score or CCTA alone compared to cohort-based risk scores can improve the allocation of lipid lowering therapy.

Clinical Value of Virtual Reality versus 3D Printing in Congenital Heart Disease.

Both three-dimensional (3D) printing and virtual reality (VR) are reported as being superior to the current visualization techniques in conveying more comprehensive visualization of congenital heart disease (CHD). However, little is known in terms of their clinical value in diagnostic assessment, medical education, and preoperative planning of CHD. This cross-sectional study aims to address these by involving 35 medical practitioners to subjectively evaluate VR visualization of four selected CHD cases in comparison with the corresponding 3D printed heart models (3DPHM). Six questionnaires were excluded due to incomplete sections, hence a total of 29 records were included for the analysis. The results showed both VR and 3D printed heart models were comparable in terms of the degree of realism. VR was perceived as more useful in medical education and preoperative planning compared to 3D printed heart models, although there was no significant difference in the ratings (p = 0.54 and 0.35, respectively). Twenty-one participants (72%) indicated both the VR and 3DPHM provided additional benefits compared to the conventional medical imaging visualizations. This study concludes the similar clinical value of both VR and 3DPHM in CHD, although further research is needed to involve more cardiac specialists for their views on the usefulness of these tools.

Left Atrial Intramural Hematoma Post-Ablation of Supraventricular Tachycardia: A Rare Complication Treated Successfully.

We report successful management of left atrial hematoma after ablation of supraventricular tachycardia. A 43-year-old female patient experienced chest pain immediately after radiofrequency ablation of a symptomatic left posterolateral accessory pathway. Transthoracic echocardiography demonstrated a large mass occupying the left atrium. Computed tomography and transesophageal echocardiography results were consistent with posterolateral intramural hematoma. She became hemodynamically unstable, requiring emergent surgery. The mass resolved completely by 6 weeks. (Level of Difficulty: Beginner.).

Trend of antibiotic susceptibility of Streptococcus pyogenes isolated from respiratory tract infections in tertiary care hospital in south Karnataka.

BACKGROUND AND OBJECTIVES: Streptococcus pyogenes is recognized as an important pathogen of respiratory tract infections. The rapidly, emerging problem of antibiotic resistant Streptococcus pyogenes is a major issue nowadays. The present study aimed to evaluate the antibiotic susceptibility of Streptococcus pyogenes isolated from upper respiratory tract infections in tertiary care hospital of south Karnataka. MATERIALS AND METHODS: A retrospective study was conducted over a period of two years. The specimens were processed by Gram staining and aerobic culture. The bacteria were isolated as per standard protocols. The minimum inhibitory values and extent of antibiotic resistance of commonly used antimicrobials were analysed for the isolated strains. RESULTS: A total of 2123 specimens were received from patients with respiratory tract infections, among which, 50 Streptococcus pyogenes isolates were obtained. Out of these, 8% were not sensitive to penicillin. Using VITEK 2 system, the prevalence of resistances to cefotaxime, erythromycin, tetracycline, levofloxacin, clindamycin and ceftriaxone were 4.2%, 83%, 51%, 8.9%, 40% and 5.3% respectively. CONCLUSION: It is important to know about the prevalence of resistance and rising MIC values of commonly used antibiotics regarding Streptococcus pyogenes to avoid therapeutic failures.

Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors.

Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice.