Cold agglutinin disease in childhood: a case series with review of literature.

Cold agglutinins are autoantibodies that target RBC antigens at temperatures below average core body temperature. They produce RBC agglutination and cold agglutinin disease (CAD), a rare form of autoimmune haemolytic anaemia. Due to it's under recognition, there is a delay between the start of symptoms and the diagnosis. With an emphasis on the laboratory approach, we provide the clinical and analytical findings from five cases of childhood CAD.

Hyperactive behaviour of growth differentiation factor- 15 (GDF-15) in conjunction with iron trafficking transporters and suppression of Nrf-2 gene in diabetes and metabolic syndrome.

Multiple parallel factors are frequently interrogated with various toxic radicals which are abundantly generated in the liver, heart, and pancreas in stress conditions. They are actively involved in the development of diabetes and metabolic aberrations. However, whether over-activation of GDF-15mRNA and influxes of iron-by-iron trafficking genes are directly suppressing the Nrf-2 gene in patients with diabetes and metabolic aberrations in context with undiagnosed individuals with diabetes and metabolic aberrations? Therefore, we have investigated inter and intra- related Zip8/14 mRNA, GDF-15mRNA, and Nrf-2 mRNA expressions in diabetes and metabolic syndrome as it is expected to be up to 134 million by 2045 in India. We recruited 120 subjects from the Department of Medicine, Endocrinology and Metabolic Clinic, All India Institute of Medical Sciences, New Delhi, India. Various investigations related to anthropometry, nutritional, hematological, biochemical, cytokine, and oxidative stress were measured in diabetes, metabolic syndrome, diabetes with metabolic aberration, and healthy controls. Relative expression of GDF-15, ZIP8, ZIP14, Nrf-2, and housekeeping genes was done in all subjects. Stress-responsive cytokines are highly expressed in patients with metabolic aberration with respect to body weight, IR, waist circumference, and fat mass. IL-1ß, TNF-α, and IL-6 levels were significantly higher in metabolic syndrome, whereas Adiponectin levels were profoundly lower side. MDA levels were significantly raised in diabetes with metabolic syndrome while SOD activities were lowered (p = 0.001). GDF-15 mRNA expression was 1.79-fold upregulated in group III as compared with Group I while 2-threefold down-regulation of Nrf-2 expression was observed in diabetes with metabolic aberration groups. Zip 8 mRNA expressions were downregulated (p = 0.014), and Zip 14 mRNA expressions were upregulated (p = 0.06) in diabetes and metabolic aberrations. The association of GDF-15 and Nrf-2 mRNA expression was found contradictory and highly interlinked with ROS. Zip 8/14mRNA expressions were also dysregulated in diabetes and metabolic-associated complications.

The Convalescent Plasma Craze! Where Does India Stand?

India becomes the country with second highest number of coronavirus disease 2019 (COVID-19) cases (59,03,932) as of September 2020. As the world debates various treatment options, the current pandemic has led to the resurgence of an ancient technique, namely convalescent plasma therapy. Although it has been in use from the late 19th century, it is an uncharted territory for most developing nations. In this article, we have discussed the pros and cons of convalescent plasma transfusion in COVID-19 patients. Articles discussed in this review have been obtained from search engines, namely PubMed, Scopus, and Embase. We have also expressed our viewpoint on the feasibility and logistical challenges of convalescent plasma use in India.

Early posttraumatic changes in coagulation and fibrinolysis systems in isolated severe traumatic brain injury patients and its influence on immediate outcome.

OBJECTIVE/BACKGROUND: Early coagulopathy in isolated severe traumatic brain injury occurs despite the lack of severe bleeding, shock, and fluid administration. We aimed to correlate coagulation activation/inhibition, thrombin generation and fibrinolysis with the development of acute trauma induced coagulopathy (TIC) and its effects on early mortality in isolated severe traumatic brain injury (iSTBI) patients. METHODS: A prospective screening of iSTBI patients was done for two years. History of anticoagulants, liver disease, hypotension, extracranial injuries, transfusion, brain death were excluded. TIC was defined as international normalized ratio (INR) ≥ 1.27 and/or prothrombin time (PT) ≥ 16.7 seconds and/or activated partial thromboplastin Time (aPTT) ≥ 28.8 seconds on admission following iSTBI. Analysis of tissue factor (TF), tissue factor pathway inhibitor (TFPI), protein C (PC), protein S (PS), thrombin/antithrombin complex (TAT), soluble fibrin monomer (sFM), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) was done. Cases were categorized as presence or absence of TIC and 20 healthy controls participants were included. RESULTS: A total of 120 cases met the inclusion criteria, aged 35.7 ±â€¯12.12 years, 96% males. TIC was identified in 50 (41.6%). TIC occurred independently of age, sex, Glasgow coma scale (GCS) but was associated with acidosis (60%; p = .01). Following iSTBI significant decline was seen in coagulation activation. Thrombin generation and fibrinolysis were markedly increased. TF, TFPI, PC and PS were low in TIC compared with control. Significant depletion of PS was seen in TIC versus No-TIC. TBI patients with depleted PS had an odds ratio (OR) of 7.10 (1.61-31.2) for TIC. Receiver operating characteristic curve (ROC) analysis depicted area under the curve (AUC) of 0.73 (95% confidence interval [CI] 0.63-0.84) with a cut-off of ≥74 of PS (specificity 63.9%, sensitivity 72.7%). In-hospital mortality was higher in TIC group (44%) compared with no-TIC (20%) with OR of 4.73 (95% CI 1.68-13.3) and hazard ratio [HR] of 2.8 (95 % CI 1.2-6.4). CONCLUSION: Incidence of TIC in iSTBI is 41.6%, with 4.7 times odds for mortality. Traumatic brain injury causes enhanced coagulation activation, inadequate inhibition, exacerbation of thrombin generation, and subsequent increased fibrinolysis. ROC curve analysis revealed a cut-off of PS ≤ 74 with specificity 63.8%, sensitivity 72.7% for development of TIC.

Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer's disease and vascular dementia.

Genetic polymorphism and epistasis play a role in etiopathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). In this case-control study, a total of 241 patients were included in the study to see the effect of paraoxonase 1 (PON1; rs662 and rs85460) and apolipoprotein E (ApoE) genes in altering the odds of having AD and VaD along with serum PON and lipid profile. The presence of at least 1 variant allele of rs662, but not rs85460, increased the risk of having AD by 1.8-fold (95% confidence interval [CI]: 0.97-3.40) and VaD by 3.09-fold (95% CI: 1.4-6.9). The interaction between PON1 genes (rs662 and rs85460) and ApoE genes showed synergistic epistasis in altering the odds of significantly having both AD and VaD. On the other hand, low serum level of high-density lipoprotein and low level of serum PON activity were found associated significantly (P ≤ .001 in both cases) only in patients with VaD as compared to healthy control.