Functional and transcriptional heterogeneity within the massively expanding HLADR+CD38+ CD8 T cell population in acute febrile dengue patients.

IMPORTANCE: CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFNγ). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR+ CD38+ phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection. Although about a third of these massively expanding HLADR+ CD38+ CD8 T cells were also CD69high when examined ex vivo, only a small fraction of them produced IFNγ upon in vitro peptide stimulation. Therefore, to better understand such functional diversity of CD8 T cells responding to dengue virus infection, it is important to know the cytokines/chemokines expressed by these peptide-stimulated HLADR+CD38+ CD8 T cells and the transcriptional profiles that distinguish the CD69+IFNγ+, CD69+IFNγ-, and CD69-IFNγ- subsets.

Leucocytosis and early organ involvement as risk factors of mortality in adults with dengue fever.

The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors.

Mortality in systemic lupus erythematosus at a teaching hospital in India: A 5-year retrospective study.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that can be life threatening. This study aimed to study the cause of mortality among admitted SLE patients over a period of 5 years at a teaching hospital in India. METHODS: A 5-year retrospective analysis of mortality in SLE patients admitted under department of medicine of our institute was done. The presenting complaints, treatment history, clinical parameters, laboratory investigations, organ involvement, systemic lupus erythematosus disease activity index (SLEDAI), and cause of mortality were collected from the medical records on a predesigned proforma. A further analysis of two groups based on the cause of mortality was done. RESULTS: In total, 53 death records were analyzed. Mortality in 28 SLE patients was due to high disease activity (Group I) and mortality in 25 patients was attributed due to both high disease activity and concomitant infection (Group II). Most of the patients were female (98%) and mean age of patient was 30.6 years. About 19 patients (35.8%) were diagnosed with SLE during hospital admission. Fever was the most common presenting complaint (69.8%) and lupus nephritis was the most common organ dysfunction seen (84.9%). Myocarditis was observed in 11 patients and 9 patients had cerebrovascular accident. The mean hemoglobin was lower in Group II (7.4 vs. 8.7 g/dL, P = 0.02). The median total leukocyte count was significantly higher in Group II (10,200 vs. 6600, P = 0.02). The mean serum urea and creatinine levels were also significantly higher in Group II (141.41 vs. 87.8 mg/dL, P = 0.006 and 4.7 vs. 1.7, P = 0.0001), respectively. The mean SLEDAI in Group I was 20.8 ± 8.9 and in Group II was17.7 ± 7.5. Bacterial pneumonia (17) was the most common infection, followed by tuberculosis (2) and fungal infection (2). CONCLUSION: Mortality among SLE patients could be due to disease flare or concomitant infection. Lung is the most common organ affected by infection in these patients.

Role of LDL apheresis in a case of homozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a form of primary hyperlipoproteinemia characterized by the presence of high concentrations of serum low density lipoprotein (LDL) cholesterol, increased tendency to form xanthomas and early onset of coronary artery disease. This disease is an autosomal dominant disorder caused by defects in the gene that encode for the LDL receptor. Homozygous familial hypercholesterolemia is a rare occurrence and here we report a case of an 18-year-old girl with familial hypercholesterolemia treated with anti-lipidemic drugs and controlled only with LDL apheresis. The patient expired after 3 months highlighting the difficulties in management due to economic constraints in a resource limited setting in spite of availability of effective therapy.

Role of Cytokines as Molecular Marker of Dengue Severity.

OBJECTIVE: Dengue infection is a rapidly spreading vector-borne disease and is endemic in the Indian subcontinent. It has varied manifestations ranging from subclinical infection to severe fatal shock syndrome. This study aimed to estimate cytokine level in dengue patients and correlate them with dengue severity. METHODS: Cases of dengue fever diagnosed in the department of medicine of our institute from July 2015 to November 2016 were included in the study. The clinical features, biochemical, hematological and radiological parameters along with cytokine levels (Interferon-gamma, Interleukin-6, and Tumour Necrosis Factor-alpha) were recorded in all patients. RESULTS: Out of 80 confirmed cases of dengue included in the study, 50 had nonsevere dengue (Group 1), and 30 patients had severe dengue (Group 2). The median level of serum TNF-α in group 2 (62.5 pg/mL) was significantly higher than the median level in group 1 (20 pg/mL), (p=0.043). Similarly, the median level of serum IFN-γ in group 2 (10.25 pg/mL) was significantly higher than the median level in group 1 (8.5 pg/mL), (p=0.002). The median level of IL-6 was also higher in group 2 (29 pg/ml) as compared group 1(14.2 pg/ml), but this result was not significant (p>0.05). CONCLUSION: Some cytokines may play a role in the pathogenesis of severe manifestations of dengue.