Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse: A Noninferiority Randomized Controlled Trial

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Coronary Artery Disease Manifestations in HIV: What,How, and Why

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.     

Mirror movements in progressive hemifacial atrophy

Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand.     

Therapeutic cooperation between auranofin,a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8^+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.     

Electroencephalographic and imaging profile in a subacute sclerosing panencephalitis (SSPE) cohort: a correlative study.

OBJECTIVE: There are only a few studies correlating diverse radiological and EEG features of subacute sclerosing panencephalitis (SSPE). The objective of the study was to (a) describe EEG profile and (b) correlate it with the clinical and imaging data of patients with confirmed SSPE. METHODS: This study was conducted at a University teaching hospital in south India and involved 58 patients (M:F=37:21, age: 12.3, SD 4.8 years) of SSPE. Diagnosis of SSPE was based on the characteristic clinical manifestations, and raised IgG (1:625) anti-measles antibody in cerebrospinal fluid (CSF) by ELISA in all the patients. Scalp EEGs were recorded on 16 channel machines using standard parameters and procedures. The EEG, clinical and imaging data were reviewed. RESULTS: EEGs were frequently abnormal: typical (37) and atypical (21). Diffuse slowing of background activity (BGA) was noted in 46 records being asymmetrical in six. Periodic complexes were periodic (32), quasi-periodic (21) or a-periodic (4). Periodic complexes (PC) (amplitude: 370.7, SD 171.2 microV; duration - 1.7, SD 2.0 s; inter-complex interval: 8.4, SD 9.2s) were symmetrical in 39 and asymmetrical in 19. CT (32) and MRI (23) scans were normal in 16 patients while others had white matter (15), cerebral edema (8), cerebral atrophy (8), basal ganglia (2), and thalamic (2) changes. There was an independent association of frontally dominant slowing of BGA (p=0.04) and typical PCs (p=0.03) with the diffuse cerebral edema on imaging. White matter changes correlated with slowing of BGA (p=0.04), but not with typical PC (p=0.16). CONCLUSIONS: This study provides valuable insight into the structural and clinical correlates of EEG changes in SSPE. SIGNIFICANCE: Irrespective of the incidence of occurrence of SSPE in a community, a clinician should be aware of the wide spectra of EEG findings. This study also discusses the possible underlying structural and clinical correlates.     

Left ventricular mass regression following aortic valve replacement with mechanical valves

Objective The degree of Left Ventricular Mass Index (LVMI) regression following aortic valve replacement correlates with long-term survival. This study aims to assess the extent of LVMI regression at 3 months following aortic valve replacement (AVR) with different types and sizes of mechanical valves in rheumatic aortic valve disease. Methods The LVMI regression was studied in 34 consecutive patients, undergoing elective AVR for rheumatic aortic stenosis and/or regurgitation. They were grouped in A and B, matched in age, body surface area and pre-operative LVMI, receiving respectively a tilting disc and a bileaflet mechanical valve. The LVMI was calculated by M-mode echocardiography using the Devereux' formula pre-operatively and three months post-operatively. The trend of LVMI reduction was compared between the two groups and amongst the patients with stenotic, regurgitant and mixed aortic valve, pathologies; and receiving different sizes of valves. Results The mean preoperative LVMI was 199g±79.5 g/m². At three months post aortic valve replacement, the mean LVMI was 130g±49.0 g/m². There was a significant reduction of LVMI post-operatively (p=0.001) at three months follow-up. The extent of LVMI regression following surgery amongst the groups A and B did not vary significantly (p=0.92). The extent of LVMI regression did not vary significantly in patients with different aortic valve pathology nor with different sizes of the valves implanted. Conclusions There is a significant early LVMI regression following aortic valve replacement in rheumatic aortic valve disease. The type and the size of the mechanical prosthesis or the rheumatic pathology do not appear to influence this regression.