Kartik Ramakrishna

Prevalence of Adult Celiac Disease in India: Regional Variations and Associations.

Objectives:Although celiac disease (CeD) affects 1% of people in the northern part of India, it is believed to be uncommon in the southern and northeastern parts because of significant differences in dietary pattern and ethnicity. We estimated the prevalence of CeD in these three populations. In a subset, we also investigated differences in the prevalence of HLA-DQ 2/8 allelotype and dietary grain consumption.Methods:A total of 23,331 healthy adults were sampled from three regions of India—northern (n=6207), northeastern (n=8149), and southern (n=8973)—and screened for CeD using IgA anti-tissue transglutaminase antibody. Positive tests were reconfirmed using a second ELISA. CeD was diagnosed if the second test was positive and these participants were further investigated. A subsample of participants was tested for HLA-DQ2/-DQ8 and underwent detailed dietary evaluation.Results:Age-adjusted prevalence of celiac autoantibodies was 1.23% in northern, 0.87% in northeastern, and 0.10% in southern India (P<0.0001). Prevalence of CeD and latent CeD, respectively, was 8.53/1,000 and 3.70/1,000 in northern, 4.66/1,000 and 3.92/1,000 in northeastern, and 0.11/1,000 and 1.22/1,000 in the southern part. The population prevalence of genes determining HLA-DQ2 and/or -DQ8 expression was 38.1% in northern, 31.4% in northeastern, and 36.4% in southern India. Mean daily wheat intake was highest in northern (455 g) compared with northeastern (37 g) or southern part (25 g), whereas daily rice intake showed an inverse pattern.Conclusions:CeD and latent CeD were most prevalent in northern India and were the least in southern India. The prevalence correlated with wheat intake and did not reflect differences in the genetic background.

Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission

Background and Aims: Scrub typhus, a zoonotic rickettsial infection, is an important reason for intensive care unit (ICU) admission in the Indian subcontinent. We describe the clinical profile, organ dysfunction, and predictors of mortality of severe scrub typhus infection. Materials and Methods: Retrospective study of patients admitted with scrub typhus infection to a tertiary care university affiliated teaching hospital in India during a 21-month period. Results: The cohort (n = 116) aged 40.0 ± 15.2 years (mean ± SD), presented 8.5 ± 4.4 days after symptom onset. Common symptoms included fever (100%), breathlessness (68.5%), and altered mental status (25.5%). Forty-seven (41.6%) patients had an eschar. Admission APACHE-II score was 19.6 ± 8.2. Ninety-one (85.2%) patients had dysfunction of 3 or more organ systems. Respiratory (96.6%) and hematological (86.2%) dysfunction were frequent. Mechanical ventilation was required in 102 (87.9%) patients, of whom 14 (12.1%) were solely managed with non-invasive ventilation. Thirteen patients (11.2%) required dialysis. Duration of hospital stay was 10.7 ± 9.7 days. Actual hospital mortality (24.1%) was less than predicted APACHE-II mortality (36%; 95% Confidence interval 32-41). APACHE-II score and duration of fever were independently associated with mortality on logistic regression analysis. Conclusions: In this cohort of severe scrub typhus infection with multi-organ dysfunction, survival was good despite high severity of illness scores. APACHE-II score and duration of fever independently predicted mortality.

Cardiac manifestations in patients with pandemic (H1N1) 2009 virus infection needing intensive care

PURPOSE To characterize the cardiac manifestations in severe pandemic (H1N1) 2009 virus [P(H1N1)2009v] infection. MATERIALS AND METHODS Adult patients admitted to the intensive care unit were recruited. Patients with an elevated troponin I (>1.5 ng/mL) and those requiring vasoactive agents had an echocardiogram. Myocardial injury was defined as elevated troponin I. Patients with reduced ejection fraction lower than 50% were diagnosed as having left ventricular systolic dysfunction. Myocarditis was presumed when myocardial injury was associated with global myocardial dysfunction. Myocardial injury and dysfunction were correlated with mortality and expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS Thirty-seven patients presented at 6.4 (SD 3.2) days of illness. Four patients had valvular heart disease and 1 preexisting ischemic heart disease. Seventeen (46%) patients had evidence of myocardial injury. Twenty of 28 patients in whom an echocardiogram was clinically indicated had left ventricular systolic dysfunction. Of these, 14 patients were diagnosed as having myocarditis, and most of them (12 patients) developed it early. Myocarditis was associated with longer duration of vasoactive agents (OR 1.46, 95% CI 1.06-2.02) and mortality. Patients with elevated troponin I had an increased risk of death (OR 8.7, 95% CI 1.5-60). A higher mortality was observed in patients with left ventricular systolic dysfunction (OR 9.6, 95% CI 1.7-58) compared with those in whom an echocardiogram was normal or not indicated. CONCLUSION In our cohort of severe P(H1N1)2009v infection, myocardial injury and dysfunction was frequent and associated with high mortality.

Incidence and risk factor evaluation of exposure keratopathy in critically ill patients: A cohort study

PURPOSE Recent emphasis on eye care in intensive care unit (ICU) patients has translated to eye assessment being part of routine care. In this setting, we determined the incidence, risk factors, and resolution time of exposure keratopathy. METHODS In this prospective cohort study, 301 patients were examined within 24 hours of ICU admission and subsequently daily by an ophthalmologist till death or discharge. Eyelid position, conjunctival and corneal changes, treatment, and outcome data were collected. RESULTS Admission diagnoses included febrile illnesses (35.2%) and respiratory failure (32.6%); 84.1% were ventilated. Forty-nine patients had exposure keratopathy (bilateral = 35, unilateral = 14) at admission; 35 patients developed new onset keratopathy (incidence 13.2%) 4.6 ± 2.6 days after ICU admission. In 67 patients, keratopathy was mild (punctate epithelial erosions). Macroepithelial defects (n = 9), stromal whitening with epithelial defect (n = 3), and stromal scar (n = 3) were infrequent. None developed microbial keratitis. On multivariate logistic regression analysis, eyelid position (odds ratio, 2.93; 95% confidence interval, 1.37-6.25), and ventilation duration (odds ratio, 1.11; 95% confidence interval, 1.04-1.19) were strongly associated with the development of keratopathy after ICU admission. Keratopathy resolved in 3.6 ± 4.5 days. CONCLUSIONS Severe exposure keratopathy is infrequent in a protocolized ICU setting. Eyelid position and duration of ventilation are associated with exposure keratopathy.

Clinical Profile and Predictors of Mortality of Severe Pandemic (H1N1) 2009 Virus Infection Needing Intensive Care: A Multi-Centre Prospective Study from South India.

Background: This multi-center study from India details the profile and outcomes of patients admitted to the intensive care unit (ICU) with pandemic Influenza A (H1N1) 2009 virus [P(H1N1)2009v] infection. Materials and Methods: Over 4 months, adult patients diagnosed to have P(H1N1)2009v infection by real-time RT-PCR of respiratory specimens and requiring ICU admission were followed up until death or hospital discharge. Sequential organ failure assessment (SOFA) scores were calculated daily. Results: Of the 1902 patients screened, 464 (24.4%) tested positive for P(H1N1)2009v; 106 (22.8%) patients aged 35±11.9 (mean±SD) years required ICU admission 5.8±2.7 days after onset of illness. Common symptoms were fever (96.2%), cough (88.7%), and breathlessness (85.9%). The admission APACHE-II and SOFA scores were 14.4±6.5 and 5.5±3.1, respectively. Ninety-six (90.6%) patients required ventilation for 10.1±7.5 days. Of these, 34/96 (35.4%) were non-invasively ventilated; 16/34 were weaned successfully whilst 18/34 required intubation. Sixteen patients (15.1%) needed dialysis. The duration of hospitalization was 14.0±8.0 days. Hospital mortality was 49%. Mortality in pregnant/puerperal women was 52.6% (10/19). Patients requiring invasive ventilation at admission had a higher mortality than those managed with non-invasive ventilation and those not requiring ventilation (44/62 vs. 8/44, P<0.001). Need for dialysis was independently associated with mortality (P=0.019). Although admission APACHE-II and SOFA scores were significantly (P<0.02) higher in non-survivors compared with survivors on univariate analysis, individually, neither were predictive on multivariate analysis. Conclusions: In our setting, a high mortality was observed in patients admitted to ICU with severe P(H1N1)2009v infection. The need for invasive ventilation and dialysis were associated with a poor outcome.

Elevated procalcitonin is associated with increased mortality in patients with scrub typhus infection needing intensive care admission

Context: Procalcitonin is a biomarker of bacterial sepsis. It is unclear if scrub typhus, a rickettsial illness, is associated with elevated procalcitonin levels. Aim: To assess if scrub typhus infection is associated with high procalcitonin levels and whether high levels portend a poorer prognosis. Setting and Design: Retrospective study of patients with severe scrub typhus infection, admitted to the medical intensive care unit of a tertiary care university affiliated teaching hospital. Materials and Methods: Eighty-four patients with severe scrub typhus infection that also had procalcitonin levels were assessed. Statistical Analysis: Relationship between procalcitonin and mortality explored using univariate and multivariate analyses. Results: The mean (±standard deviation) age was 40.0 ± 15.5 years. Patients were symptomatic for 8.3 ± 4.3 days prior to presentation. The median admission procalcitonin level was 4.0 (interquartile range 1.8 to 8.5) ng/ml; 59 (70.2%) patients had levels >2 ng/ml. Invasive mechanical ventilation was required in 65 patients; 20 patients died. On univariate analysis, admission procalcitonin was associated with increased odds of death [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.03 to 1.18]. On multivariate logistic regression analysis including procalcitonin and APACHE-II score, the APACHE-II score was significantly associated with mortality (OR 1.16, 95% CI 1.06 to 1.30, P = 0.004) while a trend was observed with procalcitonin (OR 1.05, 95%CI 1.01 to 1.13, P = 0.09). The area under the receiver operating characteristic (ROC) curve, AUC, for mortality was 0.77 for procalcitonin and 0.78 for APACHE-II. Conclusions: Procalcitonin is elevated in severe scrub typhus infection and may be associated with higher mortality.

Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis

Objective: The objective of the following study is to evaluate the associations between single nucleotide polymorphisms (SNPs) in the Heat Shock Protein 70 (HSP70) gene, gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and medical intensive care unit (MICU) stay and organ failure in sepsis. Materials and Methods: MICU patients with sepsis were genotyped for rs1061581, rs2227956, rs1008438 and rs1043618 polymorphisms in HSP70 gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis or allele-specific PCR. Messenger ribonucleic acid (mRNA) expression of IL-6 and TNF-α were quantitated in peripheral blood lymphocytes. Outcomes were recorded. Results: 108 patients (48 male) aged 40.7 ± 16.0 (mean ± standard deviation) years included H1N1 infection (36), scrub typhus (29) and urosepsis (12). Seventy-one (65.7%) had dysfunction of three or more organ systems, 66 patients (61.1%) were treated by mechanical ventilation, 21 (19.4%) needed dialysis. ICU stay was 9.3 ± 7.3 days. Mortality was 38.9%. One or more SNPs were noted in 101/108 (93.5%) and organ failure was noted in only 1/7 patients without a single SNP. The A allelotypes of rs1061581 and rs1008438 were associated with hematological dysfunction (P = 0.03 and 0.07) and longer ICU stay (P = 0.05 and 0.04), whereas IL-6 and TNF-α mRNA levels were associated with central nervous system dysfunction. Conclusions: HSP70 genotypes may determine some adverse outcomes in patients with sepsis.

Risk of pandemic (H1N1) 2009 virus infection among healthcare workers caring for critically ill patients with pandemic (H1N1) 2009 virus infection

laparoscopygrouphadpreoperative chemotherapy. Data onpreoperative albumin, smoking history and diabetes were not collected. All patients but one were followed up at 30 days (one patient lost to follow-up because of a change in general practitioner). Surveillance was performed on one patient who remained an inpatient at 30 days, by reviewing the case notes and drug charts and scrutinising for evidence of SSI. PDS was performed at 4–6 weeks; an outpatient appointment with a consultant surgeonwas made by checking the clinic entry for documented evidence of infection. The two patients readmitted within the 30 day period had case notes and drug charts scrutinised for evidence of infection. When three patients were discharged home prior to 30 days post surgery and had not had an outpatient appointment, PDS was performed by contacting their general practitioners by telephone and asking whether they had prescribed antibiotics for SSI. Our case–control audit demonstrates that the SSI rates in our department are not significantly different for robotic, laparoscopic surgery (3.8%) compared with conventional laparoscopic abdominal surgery (8.7%), although too few patients were assessed to confirm any real difference and the surveillance is ongoing. We conclude that it is important to collate the PDS data on SSI when a new procedure is introduced to an institution to ensure that quality indicators such as SSI are kept under review.

Impaired toll like receptor 9 response in pulmonary tuberculosis

Background & aim Innate immune responses are important in susceptibility to pulmonary tuberculosis (TB). In order to test the hypothesis that Toll‐like receptor (TLR) 2 function would be abnormal in patients with active pulmonary TB we compared the cytokine responses of peripheral blood mononuclear cells (PBMC) to innate immune ligands in a case‐control study. Methods PBMC from 19 untreated pulmonary TB patients, 17 healthy controls, and 11 treated pulmonary TB patients, were cultured for 24 h with TLR 2 ligand (PAM‐CSK) and other TLR ligands (muramyl dipeptide, flagellin, lipopolysaccharide (LPS), CpG oligodeoxynucleotide (CpG‐ODN)). Interleukin‐8 (IL‐8) was estimated in the supernatant by ELISA. Messenger RNA expression for inflammatory cytokines was quantitated using real time PCR. Results The important findings were (1) reduced PBMC secretion of IL‐8 in response to all ligands in active TB; (2) normal to increased PBMC secretion of IL‐8 in response to all ligands except CpG ODN (TLR 9 ligand) in TB patients who had recovered; (3) absence of difference in mRNA expression for a consortium of inflammatory pathway genes between healthy controls, active pulmonary tuberculosis and treated pulmonary tuberculosis patients. Conclusion There was a generalized post‐translational suppression of the IL‐8 response to innate immune ligands in active TB. There appears to be a defect of TLR 9 signaling in patients with tuberculosis, the nature of which needs to be further explored. HighlightsIL‐8 response of PBMC to TLR 2, 4, 5 and 9 stimulation was reduced in active pulmonary tuberculosis.IL‐8 response to TLR 9 was reduced in treated pulmonary tuberculosis.Messenger RNA expression for IL‐8 was not reduced in active or treated pulmonary tuberculosis.There appears to be a post‐translational defect of IL‐8 production in active tuberculosis.There may be a defect of TLR 9 signaling in pulmonary tuberculosis.

Rapid on-site evaluation of cytology for EUS- and EBUS-guided fine-needle aspiration

Upper gastrointestinal endoscopic ultrasound (EUS)and endobronchial ultrasound (EBUS)-guided fine-needle aspiration cytology (FNAC) are being increasingly used as a safe and non-surgical method to sample tissue from mediastinal, para-aortic, and perihilar masses and lymph nodes. EUSand EBUS-guided FNAC have greatly enhanced our diagnostic armamentarium in pulmonary medicine and gastroenterology. The diagnosis of tuberculosis is confirmed by the finding of granulomatous inflammation and the isolation of Mycobacterium tuberculosis in culture by FNACofmediastinal or retroperitoneal nodes. The diagnosis and staging of malignancy are also aided by these techniques. Adequacy of tissue sampling is vital to the diagnostic yield of these procedures and has become even more crucial in an era of increasing molecular testing for genotype-targeted therapies such as evaluation of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. A number of factors are thought to be associated with yield from these procedures, such as high-volume centers, lesion site, lymph node size, positive PET scans, biopsy of more than two sites, needle size, number of passes, and expertise of the scopist [1–6]. On-site preparation and evaluation of smears by a cytopathologist during the procedure (rapid on-site evaluation [ROSE]) ensures that smears are adequately cellular and are likely to yield a diagnosis. Several studies have demonstrated that the diagnosis at on-site evaluation correlates well with the final cytopathological diagnosis. Multiple studies have shown that ROSE increases diagnostic yield by about 10% to 15% [7, 8]. ROSE has also been shown to reduce the number of needle passes performed [9]. Due to proximity to vital structures, risk of complications such as bleeding, and time, fewer needle passes may be beneficial. These benefits may be more pronounced in centers with trainees. This has led to the establishment of ROSE as the default practice in many institutions where EUS-FNA or EBUS-FNA is offered. A survey of endosonologists indicated that ROSE was used more often by US (98%) than by European (48%) or Asian (55%) respondents [10]. However, it is not clear whether ROSE will differentially impact diagnostic yield in pancreatic vs. lymph nodal disease. A meta-analysis of seven studies (one randomized) with a total of 1299 patients, comparing EUS-FNAC with and without ROSE, concluded that ROSE did not make a significant difference to cytological adequacy or diagnostic yield [11]. Although overall the number of needle passes was similar in the two groups, in the one study which was randomized, seven passes were made for cytology in the absence of ROSE compared to four passes in the presence of ROSE [12]. ROSE requires the availability of a trained cytopathologist on site at the time of the endoscopic procedure. On-site services may not necessarily be available in hospitals in developing countries, particularly those in the public sector. Furthermore, ROSE is associated with higher costs [12]. In this issue of the Journal, Sharma et al. describe their experience of EUS-FNAC without ROSE and indicate that the adequacy of the samples for diagnosis was very good, ranging from 73% for lymph nodes to 100% for mediastinal, renal, and suprarenal masses [13]. A number of parameters may be used to judge the effectiveness of EUS-FNAC. These include cytological adequacy, diagnostic yield, number of passes required for diagnosis, and diagnostic characteristics (number of true-positive, true-negative, false-positive, and false-negative observations). * Kartik Ramakrishna kartik_ramakrishna@hotmail.com