A study of the prognostic significance of platelet distribution width, mean platelet volume, and plateletcrit in cerebral venous sinus thrombosis.

Objectives: Platelets play a key role in thrombus formation and propagation and are thus implicated in the pathogenesis and morbidity of cerebral venous sinus thrombosis (CVST). A whole blood count can be used to objectively measure platelet function through platelet indices, namely, platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit. This study examined how platelet indices (PDW,MPV, and plateletcrit) affect the CVST severity and functional outcome. Materials and Methods: In this prospective, longitudinal, and observational study, 66 patients with CVST from a tertiary care referral center were enrolled. A complete blood count including platelet indices was obtained using an automated hematology analyzer. Patients with and without parenchymal abnormalities on brain imaging were classified as having severe and non-severe CVST, respectively. The modified Rankin Scale (mRS) was used to examine functional outcomes at admission and after 90 days. The patients were categorized into low mRS (0-1) and high mRS (2-6) functional groups. Results: The patients with severe CVST were older (P < 0.05) and exhibited abnormally large PDW (P < 0.05) which were statistically significant. Severe CSVT also had poor functional outcome score both at admission (P < 0.05) and 90 days later (P < 0.05) which were statistically significant. Multiple logistic regression analysis concluded age and PDW as the independent predictors of severe CVST (P < 0.05). In receiver operating characteristic curve analysis, a cutoff value of 16.5 for PDW could predict CVST severity (P < 0.05). Patients with high mRS scores at admission had significantly larger PDW. At 90 days, no association was noted between PDW and mRS scores. MPV and plateletcrit levels were similar in both the severe and non-severe CVST groups and exerted no effect on functional outcomes. PDW was significantly and inversely related to plateletcrit (P < 0.05). Conclusion: Severe CVST and PDW had a positive correlation. During the early phases of admission, PDW levels above a particular threshold were associated with poor functional outcomes; however, no such association was observed after 90 days. MPV and plateletcrit exerted no effect on CVST severity and prognosis.

Efficacy of low-dose lung radiotherapy in the management of COVID-19 patients: a randomised, open-label study.

OBJECTIVE: Evaluate role of low-dose radiotherapy (LDRT) in COVID-19 pneumonia. METHODS: Sixty-five patients 40 years or older tested positive for COVID-19 reverse transcriptase-polymerase chain reaction with mild to moderate acute respiratory distress syndrome (ARDS), were randomised 1:1, from 4 June 2021, to either best standard of care (control arm) according to the Indian Council of Medical Research guidelines or a single dose of LDRT (LDRT-0.5Gy) to both lungs along with best standard of care (experimental arm). The primary outcome was either progression to severe disease (PaO2/FiO2 ratio <100 mmHg) within 28 days of randomisation or all-cause mortality at 28 days. If the primary outcome could have been prevented, it was considered "favourable"; if not, it was considered "unfavourable." RESULTS: Thirty-three patients were allocated to experimental arm, 32 to control arm. An intention to treat analysis was performed. Unfavourable outcome was seen in 5 (15.2%) patients in experimental arm, vs , 12 (37.5%) patients in control arm, odds of an unfavourable outcome in experimental arm were 0.3, 95% CI 0.09-0.97; two-sided p = 0.04. Four and five patients died in experimental and control arm, respectively. No radiation-induced toxicity was observed. CONCLUSION: LDRT reduced the number of patients with unfavourable outcome at 28 days. ADVANCES IN KNOWLEDGE: One of the few randomised studies showing reduced unfavourable outcome in mild to moderate ARDS COVID-19 patients receiving LDRT.CTRI/2021/06/034001, Clinical Trials Registry - India (ICMR-NIMS).

A Study of Clinical Profile, Radiological and Electroencephalographic Characteristics of Sporadic Creutzfeldt-Jakob Disease From a Tertiary Care Hospital.

Background Sporadic Creutzfeldt-Jakob disease (CJD), the most common form of human prion disease, is the archetypal diagnosis in this category. However, the spectrum of possible diagnoses is wide, encompassing various treatable conditions. A lack of standardized diagnostic criteria and a tendency to opt for brain biopsies and clinical autopsies can be limiting factors in reaching a conclusive diagnosis. Objective This study aims to retrospectively analyze clinical and investigative findings in patients referred to a specialized neurology clinic exhibiting rapidly progressive dementia. These patients were ultimately diagnosed with Probable sporadic Creutzfeldt-Jakob disease (CJD) based on the 2018 CDC criteria for sporadic CJD. Materials and Methods This study included cases of CJD diagnosed based on clinical, electrophysiological, and imaging parameters at a tertiary care hospital in India from 2016 to 2020. The diagnostic criteria proposed by the CDC (Centers for Disease Control and Prevention) were employed to categorize patients as definite, probable, or possible CJD cases. All patients underwent MRI (magnetic resonance imaging) imaging and EEG ( electroencephalography) recording, while diagnostic brain biopsies were not conducted due to a lack of consent from close relatives. Results This observational descriptive study comprised four patients diagnosed with Probable sporadic CJD (sCJD), all of whom were female. The patients exhibited an age range of 57 to 75 years at the onset of the disease, with a mean age of onset at 67.5 years. Unfortunately, all patients succumbed to the disease within 6 months of its onset. Rapidly progressive dementia was a common symptom in all cases. Additionally, patient one and patient four displayed myoclonus and dystonia, patient two exhibited myoclonus and akinetic mutism, and patient three had myoclonus, chorea, and ataxia. MR brain imaging, including T2 sequence, FLAIR sequence, and DWI/ADC mapping, was performed on all patients, revealing both cortical gray matter and deep gray matter (basal ganglia) T2/FLAIR hyperintensities with DWI restriction. A cortical ribboning pattern was observed in all cases. EEG results indicated generalized delta slow waves with triphasic complexes in three patients, while patient three alone displayed periodic sharp wave complexes at a frequency of 1 per 1 - 1.5 seconds. Conclusion MRI with DWI and ADC brain mapping emerges as the most valuable diagnostic tool for patients with clinical presentations suggesting sCJD. In this study, all patients displayed restricted diffusion, as confirmed by ADC mapping. Regrettably, the characteristic features of sCJD with restricted diffusion in the cortex, thalamus, and basal ganglia may often elude detection by radiologists outside specialized centers, resulting in diagnostic delays. Conversely, when basal ganglia or cortical signal abnormalities are detected in conjunction with parenchymal swelling, alternative diagnoses such as encephalitis or lymphoma should be considered, as parenchymal swelling is not a typical feature of sCJD as revealed by MRI.

Imaging of Dentate Nucleus Pathologies: A Case Series.

The dentate nucleus is the largest cerebellar nucleus, and it controls cognition and voluntary movement. It is found in each cerebellar hemisphere medially and posterolateral to the lateral ventricle. Pathologies of the dentate nucleus can be detected using computed tomography and magnetic resonance imaging of the brain. Here, we present a case series of seven different dentate nucleus diseases and their neuroimaging findings recovered from archives of our institution.

E-pharmacophore-based virtual screening to identify GSK-3ß inhibitors.

Glycogen synthase kinase-3ß (GSK-3ß) is a serine/threonine kinase which has attracted significant attention during recent years in drug design studies. The deregulation of GSK-3ß increased the loss of hippocampal neurons by triggering apoptosis-mediating production of neurofibrillary tangles and alleviates memory deficits in Alzheimer's disease (AD). Given its role in the formation of neurofibrillary tangles leading to AD, it has been a major therapeutic target for intervention in AD, hence was targeted in the present study. Twenty crystal structures were refined to generate pharmacophore models based on energy involvement in binding co-crystal ligands. Four common e-pharmacophore models were optimized from the 20 pharmacophore models. Shape-based screening of four e-pharmacophore models against nine established small molecule databases using Phase v3.9 had resulted in 1800 compounds having similar pharmacophore features. Rigid receptor docking (RRD) was performed for 1800 compounds and 20 co-crystal ligands with GSK-3ß to generate dock complexes. Interactions of the best scoring lead obtained through RRD were further studied with quantum polarized ligand docking (QPLD), induced fit docking (IFD) and molecular mechanics/generalized Born surface area. Comparing the obtained leads to 20 co-crystal ligands resulted in 18 leads among them, lead1 had the lowest docking score, lower binding free energy and better binding orientation toward GSK-3ß. The 50 ns MD simulations run confirmed the stable nature of GSK-3ß-lead1 docking complex. The results from RRD, QPLD, IFD and MD simulations confirmed that lead1 might be used as a potent antagonist for GSK-3ß.