The relationship between skin rash and outcome in dengue.

BACKGROUND & OBJECTIVES: Dengue fever (DF) is a common cause of acute febrile illness. Skin involvement is seen in more than half of the patients. This study was aimed to compare the clinical profile and outcome in DF patients with or without skin involvement. METHODS: This study included all the patients with DF from the acute febrile illness database of a tertiary care health centre in south India. These patients were further subgrouped into SP and SN (skin involvement positive and negative) based on the presence and absence of skin rash. Differences in clinical presentation, laboratory parameters, disease course, morbidity and outcome among patients with DF with or without skin rash were recorded and analysed statistically. RESULTS: In total 387 patients (>16 yr) with DF were enrolled into the study. Among these 55 patients had evidence of skin rash. Presence of history of overt bleeding (OR = 4.96, p = 0.027) including gum bleeding (OR = 1.17, p = 0.23), epistaxis (OR = 5.52, p = 0.04), and haematuria (OR = 6.41, p = 0.01) were more among patients with SP as compared to SN. The SP patients were found to have lower levels of platelets during the disease course. Patients with SP had a higher percentage of platelet transfusion which was statistically significant. There was no difference in organ dysfunction and mortality among both the groups. INTERPRETATION & CONCLUSION: Cutaneous involvement, though common, is not pathognomonic and can help in dengue diagnosis. Adult patients with skin rash can develop worsening thrombocytopenia requiring platelet transfusion. However, there are limited data to suggest that such patients have a worse outcome and higher mortality.

Genotyping of Orientia tsutsugamushi circulating in and around Vellore (South India) using TSA 56 gene.

PURPOSE: The immunodominant TSA 56 gene of Orientia tsutsugamushi, (scrub typhus agent) has four variable regions (VD-I to VD-IV) making it useful for genotyping. This study was undertaken to determine Orientia tsutsugamushi genotypes circulating in and around Vellore using complete and partial TSA 56 gene. METHODS: Of the 162 patients positive by 47 â€‹kDa qPCR, on 21 samples PCR to amplify the complete TSA 56 gene (≈1605 bp: Long protocol) and the partial gene sequence using the Horinouchi (≈650bp) and the Furuya (≈480 bp) protocol was performed. Sanger and Nanopore sequencing was performed to obtain sequence data for assigning genotype. For 13 amplicons partial and complete gene data was obtained. RESULTS: Phylogenetic analysis of the complete gene (Long protocol) which includes VD-I to VD-IV region and partial gene (Horinouchi) which amplifies the VD-I to VD-III regions showed identical genotypes. Twelve belonged to TA763 genotype and one belongs to Karp genotype. The Furuya sequence (in silico) correctly identified the Karp genotype and 10 of the TA763 genotypes. Two TA763 genotypes (identified by complete and 650 bp partial gene analysis) were misidentified by Furuya sequence analysis as Karp genotype. CONCLUSIONS: Analysis of the 13 complete 56 â€‹kDa gene sequences suggests that TA763 is the commonest genotype in Vellore. Sanger sequencing of the 650 bp fragment gives similar results. However, these results need to be validated by larger prospective multi-centric studies.

Revised workflow practices in the management of acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic.

OBJECTIVE: To document changes in evaluation protocols for acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic, and to analyse concordance between clinical and histopathological diagnoses based on new practice guidelines. METHODS: Protocols for the evaluation of patients with suspected acute invasive fungal sinusitis both prior and during the coronavirus disease 2019 period are described. A retrospective analysis of patients presenting with suspected acute invasive fungal sinusitis from 1 May to 30 June 2021 was conducted, with assessment of the concordance between clinical and final diagnoses. RESULTS: Among 171 patients with high clinical suspicion, 160 (93.6 per cent) had a final histopathological diagnosis of invasive fungal sinusitis, concordant with the clinical diagnosis, with sensitivity of 100 per cent, positive predictive value of 93.6 per cent and negative predictive value of 100 per cent. CONCLUSION: The study highlights a valuable screening tool with good accuracy, involving emphasis on 'red flag' signs in high-risk populations. This could be valuable in situations demanding the avoidance of aerosol-generating procedures and in resource-limited settings facilitating early referral to higher level care centres.

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity.

BACKGROUND: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. OBJECTIVES: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. METHODS: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. RESULTS: The 143 patients (104 males [80%], age 54 [42 - 65] years, median [inter-quartile range]) presented 4 (3-7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 - 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 - 165], p value < 0.001). CONCLUSIONS: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.

Magnetic resonance imaging findings in a fatal case of Salmonella typhi-associated encephalopathy: a case report and literature review.

We describe MRI findings in a fatal case of culture proven Salmonella typhi-associated encephalopathy. MRI findings included symmetrical diffuse abnormal signal in centrum semiovale, periventricular and deep white matter, splenium of corpus callosum and cerebellar deep white matter with central area of restricted diffusion. There was no contrast enhancement, significant edema or mass effect. Previous literature is also reviewed for imaging findings in Salmonella associated encephalopathy.

Epidemiology and outcome of bacteremia caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. in a tertiary care teaching hospital in south India.

BACKGROUND: Production of extended spectrum beta-lactamase (ESBL) is one of the most important resistance mechanisms that hamper the antimicrobial treatment of infections caused by Enterobacteriaceae. Therefore, it is imperative to quantify the problem, and reinforce guidelines promoting appropriate antibiotic use. OBJECTIVES: To determine the prevalence, risk factors and the outcome of antibiotic treatment among hospitalized adults with bacteremia caused by ESBL producing strains of E. coli and Klebsiella spp. STUDY DESIGN: Prospective cohort study METHODS: Sequentially encountered patients bacteremias due to E. coli or Klebsiella spp. were prospectively followed up for 14 days from the diagnosis of bacteremia. RESULTS: Among the 131 bacteremic patients (62.6% nosocomially acquired), ESBL production was detected in 73.28% of the isolates of E. coli and Klebsiella spp. ESBL production was more common among isolates from patients with nosocomial infections than isolates from community acquired infections (85.37% versus 53.06%; p = < 0.001). Prior use of 3rd or 4th generation cephalosporins was associated with an increased risk of ESBL production (p = 0.017). A high degree resistance to multiple classes of antibiotics was noted. Carbapenems were the most active antibiotics in-vitro (imipenem susceptibility 99.2%). The commonest source of bacteremia was the urinary tract (45.04%). The 14-day mortality rate was 23.6%. There was no significant difference was seen in the mortality rate between E. coli and Klebsiella spp. infections, ESBL-producing and non-ESBL-producing strains, nosocomial and community acquired infections and among those treated with inappropriate antibiotics initially. CONCLUSIONS: This study shows a very high ESBL production and resistance to multiple classes of antibiotics, even among patients with community acquired infections caused by Enterobacteriaceae. The empiric use of 3rd and 4th generation cephalosporins should be curtailed, as cephalosporin use was associated with an increased risk of ESBL production. In view of their excellent in-vitro activity, carbapenems should be the initial empiric choice for serious life threatening infections caused by ESBL producing Enterobacteriaceae, with prompt de-escalation when culture and susceptibility results become available.

Eschar and IgM ELISA in the diagnosis of scrub typhus.

Scrub typhus is one of the leading causes of acute febrile illness in India. This study aimed to determine the best diagnostic tool for the identification of scrub typhus and study the possible association between diagnostics and clinical characteristics. Patients with fever of ≤15 days admitted to the hospital satisfying the case definition of 47 kDa quantitative polymerase chain reaction (qPCR) positivity OR scrub typhus IgM ELISA positivity along with the presence of eschar OR Scrub typhus IgM ELISA positivity along with defervescence of fever within 72 h of initiation of specific therapy were recruited. Of the 116 patients satisfying the case definition, 47 kDa qPCR was positive in 43 (37%) patients, whereas IgM ELISA was positive in 104 (90%) patients and eschar was seen in 59 (51%) patients. The median duration of fever was 7.5 days (interquartile range 6-10 days). Multiorgan dysfunction syndrome (MODS) was described in 44 (37.9%) patients. Two patients (1.8%) succumbed to the illness. Presence of eschar and IgM ELISA positivity were detected in 106 (91%) cases. Scrub typhus, even with MODS, has low mortality because of immediate institution of specific therapy due to physician awareness. The presence of eschar and IgM ELISA positivity can be used to detect a majority of cases of scrub typhus.

Rodenticidal hepatotoxicity: Raised plasma Von Willebrand factor levels predict in-hospital survival and preliminary report of the outcome of Von Willebrand factor reducing management protocol.

BACKGROUND: High Von Willebrand factor (VWF) levels may predispose to multi-organ failure in acute liver failure (ALF). In rodenticide-induced hepatotoxicity patients, we analyzed if plasma VWF levels predicted survival and also the outcome of VWF lowering by N-acetyl cysteine (NAC), fresh frozen plasma (FFP) infusions, and plasma exchange (PLEX). METHODS: We retrospectively analyzed prospectively collected data. Hepatotoxicity was classified as uncomplicated acute hepatitis (UAH), acute liver injury (ALI), and ALF. ALF patients, if not opting for liver transplantation, had PLEX and NAC; ALI patients received NAC ± FFP (PLEX, if worsening); UAH patients had NAC. Plasma VWF antigen was measured (normal, 50% to 150%). In-hospital survival was analyzed as discharged alive or died/discharged in a terminal condition (poor outcome). RESULTS: Twenty-four consecutive rodenticide-induced hepatotoxicity patients (UAH in 1, ALI in 20, ALF in 3) from December 2017 to January 2019 were studied. Baseline VWF levels were 153%, 423 (146-890)% median (range), and 448 (414-555)% in UAH, ALI, ALF patients; model for end-stage liver disease (MELD) scores were 11, 24 (12-38), 36 (32-37) and in-hospital survival rates were 100%, 85%, 67%, respectively. VWF levels were higher in patients with poor outcome (555 [512-890]%) than in those discharged alive (414 [146-617]%) (p-value = 0.04). The area under the receiver operating curve of the VWF level, MELD score, and sequential organ failure assessment score to predict survival was 0.92, 0.84, and 0.66, respectively. Of 4 patients meeting criteria for liver transplantation (none had transplantation), 3 (75%) survived. CONCLUSIONS: High VWF levels predict poor outcome in rodenticide-induced hepatotoxicity. VWF reduction may be useful in such patients.

A retrospective study on epidemiology of hypoglycemia in Emergency Department.

BACKGROUND: Hypoglycemia is one among the leading causes for Emergency Department (ED) visits and is the most common and easily preventable endocrine emergency. This study is aimed at assessing the incidence and elucidating the underlying causes of hypoglycemia. MATERIALS AND METHODS: A retrospective, observational study which included patients registering in ED with a finger prick blood glucose ≤60 mg/dl at the time of arrival. All patients aged above 15 years with the above inclusion criteria during the period of August 2010 to July 2013 were selected. The study group was categorized based on diabetic status into diabetic and nondiabetic groups. RESULTS: A total of 1196 hypoglycemic episodes encountered at the ED during the study period were included, and of which 772 with complete data were analyzed. Underlying causes for hypoglycemia in the diabetic group (535) mainly included medication related 320 (59.81%), infections 108 (20.19%), and chronic kidney disease 61 (11.40%). Common underlying causes of hypoglycemia in nondiabetic group (237, 30.69%) included infections 107 (45.15%), acute/chronic liver disease 42 (17.72%), and malignancies 22 (9.28%). Among diabetic subjects on antidiabetic medications (n = 320), distribution over 24 h duration clearly reported two peaks at 8th and 21st h. The incidence of hypoglycemia and death per 1000 ED visits were 16.41 and 0.73 in 2011, 16.19 and 0.78 in 2012, 17.20 and 1.22 in 2013 with an average of 16.51 and 0.91, respectively. CONCLUSION: Bimodal distribution with peaks in incidences of hypoglycemic attacks at 8th and 21st h based on hourly distribution in a day can be correlated with the times just before next meal. None of the patients should leave ED without proper evaluation of the etiology of hypoglycemia and the problem should be addressed at each individual level. Increasing incidence of death over the years is alarming, and further studies are needed to conclude the root cause.

Changing paradigm of cryptococcal meningitis: an eight-year experience from a tertiary hospital in South India.

BACKGROUND: Cryptococcal meningitis (CM) is a common opportunistic fungal infection causing sub-acute meningitis with the potential for complications and significant mortality. We conducted this study to describe the difference in presentation and outcome between HIV-infected and HIV-uninfected patients. MATERIALS AND METHODS: Patients admitted to a tertiary care centre between 2005 and 2013 with confirmed CM were included in the analysis. Details of the clinical presentation, laboratory findings, treatment details, risk factors for infection and outcome were documented and analysed. RESULTS: During the study period, 102 (87.2%) cases of CM occurred among HIV infected individuals, whereas 15 (12.8%) occurred among HIV-uninfected patients. HIV-infected patients with CM were younger compared with HIV-uninfected patients (38.2 ± 8.5 years vs. 45 ± 11.5 years; P = 0.07). The median duration of symptoms prior to presentation was shorter in the HIV-infected group (20 ± 32 vs. 30 ± 42; P = 0.03). There was no difference between the cerebrospinal fluid (CSF) lymphocyte counts, CSF protein counts, and CSF sugar levels in both the groups. The diagnostic yield of Cryptococcus was similar with CSF India ink smear (89% vs. 87%), CSF fungal culture (95% vs. 87%), and blood culture (100% vs. 75%) in both the groups. Case fatality rate in the HIV-infected group was 30.6%, whereas there were no deaths in the HIV-uninfected group. CONCLUSION: HIV-infected patients with CM have a worse outcome compared to HIV-uninfected patients. The overall trend over 3 decades shows increasingly successful rates of treatment and hence early diagnosis and treatment are of paramount importance.

Organophosphate-pyrethroid combination pesticides may be associated with increased toxicity in human poisoning compared to either pesticide alone.

BACKGROUND: Organophosphate (OP) poisoning results in significant toxicity while pyrethroid poisoning is associated with extremely low fatality. OPs can inhibit the detoxification of pyrethroid and increase the toxicity of the combination. We assessed whether mixed OP-pyrethroid poisoning impacted outcome in human poisoning. METHODS: Patients were identified from a prospectively collected institutional poisoning database that incorporates demographic and outcome data of patients presenting with poisoning. RESULTS: Of the 1177 poisoned patients admitted over 2 years, 32 presented with OP-pyrethroid (50% chlorpyrifos-5% cypermethrin mixture) poisoning (Group 1), 26 consumed 20% chlorpyrifos (Group 2), and 32 took 15% cypermethrin (Group 3). Seizures occurred in 15.6% (n = 5) with chlorpyrifos-cypermethrin poisoning, 18.8% (n = 6) with cypermethrin poisoning, and 3.9% (n = 1) with chlorpyrifos poisoning. Ventilatory requirements were 53.5% (17/32), 42.3% (11/26), and 15.7% (5/32) in Groups 1-3, respectively. Ventilator-free days (Mean ± SD) was significantly lower (p < 0.006) in Group 1 (20.9 ± 9.3 days) than those in Group 2 (26.1 ± 4.4 days) or 3 (27.8 ± 0.6). The median (inter-quartile range) hospital stay was 5.5 (4-19.5), 5 (5-6), and 1 (0.65-1.5) days, respectively, in the three groups. Four patients died in Group 1 (13%). None died in the other groups. CONCLUSION: Although confounded by the varying quantity of chlorpyrifos and cypermethrin in the different formulations, patients with mixed poisoning appear to have shorter ventilator-free days than patients poisoned by either of the pesticides alone. Further studies are required comparing patients poisoned by formulations with similar quantities of OP and pyrethroid or with analysis of blood pesticide concentration on admission.

A probable case of acquired toxoplasmosis presenting as pyrexia of unknown origin in an immunocompetent individual.

Disseminated toxoplasmosis presenting as a prolonged febrile illness is rare in immunocompetent individuals. We report a probable case of acquired toxoplasmosis in an immunocompetent woman who presented with fever of 6 months duration with lymphadenopathy and splenomegaly. The diagnosis was confirmed by serology and the presence of Toxoplasma gondii tachyzoites on bone marrow aspirate. The patient was successfully treated with pyrimethamine plus clindamycin.

Performance of clinical scoring systems in acute organophosphate poisoning.

INTRODUCTION: Clinical scoring systems are used to predict mortality rate in hospitalized patients. Their utility in organophosphate (OP) poisoning has not been well studied. METHODS: In this retrospective study of 396 patients, we evaluated the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Simplified Acute Physiology Score (SAPS) II, Mortality Prediction Model (MPM) II, and the Poisoning Severity Score (PSS). Demographic, laboratory, and survival data were recorded. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated to study the relationship between individual scores and mortality rate. RESULTS: The mean (standard deviation) age of the patients was 31.4 (12.7) years, and at admission, their pseudocholinesterase (median, interquartile) level was 317 (222-635) U/L. Mechanical ventilation was required in 65.7% of the patients and the overall mortality rate was 13.1%. The mean (95% confidence interval) scores were as follows: APACHE-II score, 16.4 (15.5-17.3); SAPS-II, 34.4 (32.5-36.2); MPM-II score, 28.6 (25.7-31.5); and PSS, 2.4 (2.3-2.5). Overall, the AUC for mortality was significantly higher for APACHE-II (0.77) and SAPS-II (0.77) than the PSS (0.67). When patients were categorized, the AUCs were better for WHO Class II (0.71-0.82) than that for Class I compounds (0.60-0.66). For individual compounds, the AUC for APACHE-II was highest in quinalphos (0.93, n = 46) and chlorpyrifos (0.86, n = 38) and lowest in monocrotophos (0.60, n = 63). AUCs for SAPS-II and MPM-II were marginally but not significantly lower than those for APACHE-II. The PSS was generally a poorer discriminator compared to the other scoring systems across all categories. CONCLUSIONS: In acute OP poisoning, the generic scoring systems APACHE-II and SAPS-II outperform the PSS. These tools may be used to predict the mortality rate in OP poisoning.