The relationship between the size and asymmetry of the lateral ventricles and cortical myelin content in individuals with mood disorders.

Background: Although enlargement of the lateral ventricles was previously observed in individuals with mood disorders, the link between ventricular size and asymmetry with other indices of brain structure remains underexplored. In this study, we examined the association of lateral ventricular size and asymmetry with cortical myelin content in individuals with bipolar (BD) and depressive (DD) disorders compared to healthy controls (HC). Methods: Magnetic resonance imaging (MRI) was used to obtain T1w and T2w images from 149 individuals (age=27.7 (SD=6.1) years, 78% female, BD=38, DD=57, HC=54). Cortical myelin content was calculated using the T1w/T2w ratio. Elastic net regularized regression identified brain regions whose myelin content was associated with ventricular size and asymmetry. A post-hoc linear regression examined how participants' diagnosis, illness duration, and current level of depression moderated the relationship between the size and asymmetry of the lateral ventricles and levels of cortical myelin in the selected brain regions. Results: Individuals with mood disorders had larger lateral ventricles than HC. Larger ventricles and lower asymmetry were observed in individuals with BD who had longer lifetime illness duration and more severe current depressive symptoms. A greater left asymmetry was observed in participants with DD than in those with BD (p<0.01). Elastic net revealed that both ventricular enlargement and asymmetry were associated with altered myelin content in cingulate, frontal, and sensorimotor cortices. In BD, but not other groups, ventricular enlargement was related to altered myelin content in the right insular regions. Conclusions: Lateral ventricular enlargement and asymmetry are linked to myelin content imbalance, thus, potentially leading to emotional and cognitive dysfunction in mood disorders.

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.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

The interaction between depression diagnosis and BMI is related to altered activation pattern in the right inferior frontal gyrus and anterior cingulate cortex during food anticipation.

BACKGROUND: Depression and overweight/obesity often cooccur but the underlying neural mechanisms for this bidirectional link are not well understood. METHODS: In this functional magnetic resonance imaging study, we scanned 54 individuals diagnosed with depressive disorders (DD) and 48 healthy controls (HC) to examine how diagnostic status moderates the relationship between body mass index (BMI) and brain activation during anticipation and pleasantness rating of food versus nonfood stimuli. RESULTS: We found a significant BMI-by-diagnosis interaction effect on activation in the right inferior frontal gyrus (RIFG) and anterior cingulate cortex (ACC) during food versus nonfood anticipation (p < .0125). Brain activation in these regions was greater in HC with higher BMI than in HC with lower BMI. Individuals with DD showed an opposite pattern of activation. Structural equation modeling revealed that the relationship between BMI, activation in the RIFG and ACC, and participants' desire to eat food items shown in the experiment depended on the diagnostic status. CONCLUSIONS: Considering that food anticipation is an important component of appetitive behavior and that the RIFG and ACC are involved in emotion regulation, response inhibition and conflict monitoring necessary to control this behavior, we propose that future clinical trials targeting weight loss in DD should investigate whether adequate mental preparation positively affects subsequent food consumption behaviors in these individuals.

Evidence for intensive LDL-C lowering for acute coronary syndrome: Recommendations from the Lipid Association of India.

Patients with acute coronary syndrome (ACS) have a high risk of subsequent adverse cardiovascular outcomes, particularly within the first 30 days. Although it is well documented that initiation of statin therapy in the setting of ACS improves short- and long-term cardiovascular outcomes, and achievement of lower levels of low density lipoprotein cholesterol (LDL-C) incrementally improves outcomes, many patients with ACS have persistent hypercholesterolemia after discharge from the hospital. This is a missed opportunity that prompted the Lipid Association of India to develop recommendations for earlier initiation of more aggressive LDL-C lowering treatment, particularly for patients of South Asian descent who are well-documented to have earlier onset of more aggressive atherosclerotic cardiovascular disease. The Lipid Association of India recommends individualized aggressive LDL-C goals after ACS, which can be rapidly achieved with high intensity statin therapy and subsequent goal-directed adjunctive treatment with ezetimibe and PCSK9 inhibitors. Improved treatment of hypercholesterolemia achieved within weeks after ACS has the potential to reduce the high rate of morbidity and mortality in these high risk patients.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): a good practice guide, pictorial review, and new perspectives.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but emerging T-cell non-Hodgkin lymphoma. It has two distinct subtypes, "effusion-only" or "mass-forming" disease, arising around implants in patients with in situ or previous history of textured-surface breast implants. The clinical, histopathological and imaging features are unique and nuanced as compared to primary breast malignancy and other lymphoma categories. Prompt recognition and diagnosis triggers referral to appropriate BIA-ALCL centres and initiation of treatment, with potential for excellent prognosis. Definitive management of both subtypes involves implant and capsule removal; systemic therapy is reserved for mass-forming disease and advanced-stage disease. There have been recent crucial advances in the diagnostic pathway, with publication of national and international guidelines: from the UK Medicines Healthcare products Regulatory Agency (MHRA) Plastic, Reconstructive and Aesthetic Surgery Expert Advisory Group (PRASEAG), and the United States National Comprehensive Cancer Network (NCCN). This review provides a practical guide to the clinical work-up of BIA-ALCL, enabling optimisation of the diagnostic imaging pathway, with representative cases.

Communication Lower-Bounds for Distributed-Memory Computations for Mass Spectrometry based Omics Data.

Mass spectrometry (MS) based omics data analysis require significant time and resources. To date, few parallel algorithms have been proposed for deducing peptides from mass spectrometry-based data. However, these parallel algorithms were designed, and developed when the amount of data that needed to be processed was smaller in scale. In this paper, we prove that the communication bound that is reached by the existing parallel algorithms is Ω ( m n + 2 r q p ) , where m and n are the dimensions of the theoretical database matrix, q and r are dimensions of spectra, and p is the number of processors. We further prove that communication-optimal strategy with fast-memory M = m n + 2 q r p can achieve Ω ( 2 m n q p ) but is not achieved by any existing parallel proteomics algorithms till date. To validate our claim, we performed a meta-analysis of published parallel algorithms, and their performance results. We show that sub-optimal speedups with increasing number of processors is a direct consequence of not achieving the communication lower-bounds. We further validate our claim by performing experiments which demonstrate the communication bounds that are proved in this paper. Consequently, we assert that next-generation of provable, and demonstrated superior parallel algorithms are urgently needed for MS based large systems-biology studies especially for meta-proteomics, proteogenomic, microbiome, and proteomics for non-model organisms. Our hope is that this paper will excite the parallel computing community to further investigate parallel algorithms for highly influential MS based omics problems.

Quantifying Distances Between Non-Elliptical Clusters to Enhance the Identification of Meaningful Emotional Reactivity Subtypes.

Coordinated emotional responses across psychophysiological and subjective indices is a cornerstone of adaptive emotional functioning. Using clustering to identify cross-diagnostic subgroups with similar emotion response profiles may suggest novel underlying mechanisms and treatments.However, many psychophysiological measures are non-normal even in homogenous samples, and over-reliance on traditional elliptical clustering approaches may inhibit the identification of meaningful subgroups. Finite mixture models that allow for non-elliptical cluster distributions is an emerging methodological field that may overcome this hurdle. Furthermore, succinctly quantifying pairwise cluster separation could enhance the clinical utility of the clustering solutions. However, a comprehensive examination of distance measures in the context of elliptical and non-elliptical model-based clustering is needed to provide practical guidance on the computation, benefits, and disadvantages of existing measures. We summarize several measures that can quantify the multivariate distance between two clusters and suggest practical computational tools. Through a simulation study, we evaluate the measures across three scenarios that allow for clusters to differ in location, scale, skewness, and rotation. We then demonstrate our approaches using psychophysiological and subjective responses to emotional imagery captured through the Transdiagnostic Anxiety Study. Finally, we synthesize findings to provide guidance on how to use distance measures in clustering applications.

Renal denervation therapy for hypertension: truths and half-truths: Renal denervation therapy for hypertension.

Systemic hypertension is a major contributing factor for excessive morbidity and mortality globally. Experimental studies and early clinical trials showed excellent therapeutic responses to renal denervation (RDN) in patients with hypertension. However meta-analyses and objective assessments have failed to show that RDN therapy has any significant effect on blood pressure.  The aim of this review is to introduce the different methods that can be used in RDN, along with the benefits and disadvantages of these methods. Radiofrequency (RF) ablation (of renal nerves) is the most com-mon method of RDN, and we discuss the clinical evaluation of this method in the SYMPLICITY RDN trials. Finally, the development of second-generation RF devices and more comprehensive RDN procedures lead us to consider the current status and future path for RDN.

Morality-Based Assertion and Homophily on Social Media: A Cultural Comparison Between English and Japanese Languages.

Moral psychology is a domain that deals with moral identity, appraisals and emotions. Previous work has primarily focused on moral development and the associated role of culture. Knowing that language is an inherent element of a culture, we used the social media platform Twitter to compare moral behaviors of Japanese tweets with English tweets. The five basic moral foundations, i.e., Care, Fairness, Ingroup, Authority, and Purity, along with the associated emotional valence were compared between English and Japanese tweets. The tweets from Japanese users depicted relatively higher Fairness, Ingroup, and Purity, whereas English tweets expressed more positive emotions for all moral dimensions. Considering moral similarities in connecting users on social media, we quantified homophily concerning different moral dimensions using our proposed method. The moral dimensions Care, Authority, and Purity for English and Ingroup, Authority and Purity for Japanese depicted homophily on Twitter. Overall, our study uncovers the underlying cultural differences with respect to moral behavior in English- and Japanese-speaking users.

Retrospective, Observational Study to Determine the Choice of Antihypertensive agent According to Stage of Hypertension, Risk factors and Co-morbidities in Real World Setting in India: A Report of Baseline Data.

BACKGROUND: The present study intended to estimate the comorbidities and risk factors among patients with hypertension in India. Further, the current practice of hypertension management was evaluated and the choice of therapy was assessed based on hypertension grade, risk factors, and comorbidities. METHODS: Electronic medical record data (June 2017-June 2019) of Indian adult hypertensive patients (≥140/90 mmHg) who had two blood pressure (BP) readings were retrospectively analyzed. Demographic characteristics, BP readings, comorbidities, medications and co-medications, and laboratory data were collected at baseline. Grids based on hypertension grade (I, II, and III), demographic factors, risk factors, and comorbidities were created and prescribed antihypertensive drugs (AHDs) in each grid were evaluated. RESULTS: Among 100,075 patients, the proportion of patients in 18-40 year, 40-65 year, and >65 year age groups were 11.4%, 65.1%, and 23.4%, respectively. Proportion of men and women was similar (52.0% vs 47.9%). Proportion of patients with BMI <25 Kg/m2 was 8.1%, 25-29.9 Kg/m2 was 11.9%, and >30 Kg/m2 was 8.8%. Mean BP of patients with hypertension was: grade I (145.05/90.73 mmHg), grade II (160.07/95.64 mmHg), and grade III (180.82/102.76 mmHg). Mean low density lipoprotein (113.26 mg/dL), serum creatinine (2.28 mg/dL), mean HbA1c (8.7%) levels were highest among patients with grade III hypertension. Commonly observed comorbidities were type 2 diabetes mellitus (T2DM: 51.5%), dyslipidemia (36.4%), and chronic kidney disease (CKD: 4.4%). Top concomitant medications included anti-diabetic therapies (34.6%), drugs for dyslipidemia (30.0%), and anti-platelet therapies (6.9%). CONCLUSION: Most prescribed AHD monotherapies were angiotensin receptor II blockers (ARBs) and calcium channel blockers (CCBs) and most prescribed combination therapies were ARBs + diuretics and ARBs + CCBs. Telmisartan and amlodipine+telmisartan for patients with comorbid T2DM or dyslipidemia and metoprolol for those with coronary artery disease were the commonly prescribed AHDs.

Chronic lymphocytic leukaemia and Richter's transformation: multimodal review and new imaging paradigms.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults. It is a malignancy of CD5 B-cells characterised by small, mature-appearing lymphocytes accumulating in the blood, bone marrow, and lymphoid tissues. Richer transformation (RT) is an important adverse complication. Detection of RT is critical to allow initiation of appropriate therapy. CLL staging and response evaluation is complicated and nuanced. From our extensive tertiary centre experience of several hundred CLL cases over the last decade, we detail key computed tomography (CT) and positron-emission tomography (PET) imaging features of the natural history of CLL. The authors present an original imaging-based patient-management paradigm for the investigation of potential RT, which will inform global practice. Potential applications of whole-body diffusion weighted imaging, novel PET radiotracers, minimal residual disease, and ct-DNA are addressed.

Current and future best practice in imaging, staging, and response assessment for Non-Hodgkin's lymphomas: the Specialist Integrated Haematological Malignancy Imaging Reporting (SIHMIR) paradigm shift.

Non-Hodgkin's lymphoma (NHL) encompasses over 40 different haematological malignancies, including low and high-grade neoplasms, such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) respectively. A key clinical issue in the context of NHL is delayed and inaccurate diagnosis, which contributes adversely to patient morbidity and mortality. This article will address relevant imaging aspects, with particular reference to advancements in NHL imaging, including computed tomography (CT), integrated positron-emission tomography (PET)-CT, and magnetic resonance imaging (MRI). We provide multiparametric (anato-functional) imaging display items, including histological correlation. We will also introduce our original concept of "Specialist Integrated Haematological Malignancy Imaging Reporting" (SIHMIR), a paradigm shift in lymphoma radiology.

Asian Pacific Society of Cardiology Consensus Recommendations on Dyslipidaemia.

The prevalence of dyslipidaemia has been increasing in the Asia-Pacific region and this is attributed to dietary changes and decreasing physical activity. While there has been substantial progress in dyslipidaemia therapy, its management in the region is hindered by limitations in awareness, adherence and healthcare costs. The Asian Pacific Society of Cardiology (APSC) developed these consensus recommendations to address the need for a unified approach to managing dyslipidaemia. These recommendations are intended to guide general cardiologists and internists in the assessment and treatment of dyslipidaemia and are hoped to pave the way for improving screening, early diagnosis and treatment. The APSC expert panel reviewed and appraised the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. The resulting consensus recommendations tackle contemporary issues in the management of dyslipidaemia, familial hypercholesterolaemia and lipoprotein(a) in the Asia-Pacific region.

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.