Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) mutation and EBV-associated T-cell lymphoproliferative disorder of the thyroid

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%­50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein­Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.

Aetiology, outcomes & predictors of mortality in acute respiratory distress syndrome from a tertiary care centre in north India.

Background & objectives: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. Methods: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed. Results: Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%).Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (Ppeak) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission. Interpretation & conclusions: Bacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and Ppeak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality.

Central venous catheter related bloodstream infections in medical intensive care unit patients in a tertiary referral centre.

Aims. To determine the incidence of central line associated bloodstream infections (CLABSIs) in the medical intensive care unit (ICU) and ward setting at All India Institute of Medical Sciences (AIIMS), New Delhi. Settings and Design. The study was conducted in the medical ICU, a 9-bedded ICU at the AIIMS, a tertiary care teaching hospital. The study design was a prospective observational study. Methods. One hundred patients admitted to medical ICU and the ward at AIIMS with an indwelling, non-tunnelled central venous catheter (CVC) in place at admission and those with a hospital stay with indwelling CVC for more than 48 hours were monitored. These patients were followed daily for the development of new onset sepsis 48 hours after insertion of CVC, in which case three sets of blood samples for culture were drawn over a span of 24 hours. Statistical Methods. Incidence of CLABSIs was measured per 1000 central line days. Results. One hundred patients hospitalised for an aggregate 1119 days acquired 29 hospital-acquired infections (HAIs), a rate of 38.8% or 31.2 HAIs per 1000 hospital days. The incidence of bloodstream infections (BSIs) in this group was 6.8%. No case of laboratory confirmed CLABSIs could be demonstrated. Incidence of clinical sepsis was 27.6% or 8.2 per 1000 CVC days. There were 9 cases out of the 29 patients (39.7%) who had evidence of HAIs with no apparent focus of infection. Only one of these cases had evidence of BSI with isolation of Staphylococcus aureus in both CVC tip culture and the simultaneous blood culture; however the antibiograms were different. Conclusions. The low rate of BSIs in the present study and the absence of occurrence of a laboratory confirmed CLABSI should be interpreted in the light of the small sample size of the study and the multitude of antibiotics received before the development of HAI.

A two-site hospital-based study on factors associated with nonadherence to highly active antiretroviral therapy.

Objectives : To describe the pattern of adherence to Highly Active Antiretroviral therapy (HAART) and ascertain the factor(s) associated with nonadherence. Methods: This was a cross-sectional, two-site, hospital-based study. The study was undertaken in 2005; as a result of phased roll out of free HAART as part of National AIDS Control Program, patients at Lok Nayak Jai Prakash (LNJP) hospital were receiving free HAART, while patients at All India Institute of Medical Sciences (AIIMS) had to bear out-of-pocket expenses for HAART. Adherence was defined as not having missed even a single pill over the previous 4-day period on self-reporting. Results: Adherence at AIIMS was 47%, whereas it was 90% at LNJP. The difference was statistically significant. Multivariate analysis showed that nonadherence was associated with not having been told about the importance of HAART, having to pay out-of-pocket for HAART and reported continued risk behavior post HAART. Conclusion: With the provision of free HAART, adherence is likely to be high. Emphasis should be given on simultaneous recruitment of counselors, and physicians should be made aware about the need to inquire and counsel patients against continued risk behavior.