Implications of CD45RA and CD45RO T cell subsets in patients of chronic rhinosinusitis with nasal polyposis infected with Aspergillus flavus.

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps. The study included 50 cases of CRSwNP and 50 healthy controls. Biopsies were subjected to KOH and culture for mycological investigation. We examined the changes in T helper (CD4+) and T cytotoxic (CD8+) in total T cells (CD3+) and expression of naive (CD45RA) and memory (CD45RO) cell markers in T cell subsets in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens in cases before and after treatment and in healthy controls by flow cytometry. Predominantly, A. flavus (86%) identified in nasal polyp biopsies of patients. An increased percentage of CD3+CD4+ T cells observed after A. flavus stimulation in patients when compared with healthy controls. The expression of CD4+CD45RA+ cells was significantly (P < .05) reduced in patients and increased CD4+CD45RO+ was observed upon stimulation with A. flavus in patients when compared with healthy control. Continuous exposure to inhaled fungal spores may induce aberrant immune responses to A. flavus spores, causing an allergic immunological reaction with high CD4+T cell responses, resulting in an unfavourable outcome. Elevated CD4+CD45RO+ T cells may transform the pathogenic response and highlight the chances of A. flavus reactive T cells involvement in prompting inflammation in CRSwNP.

Immunogenicity of measles-rubella vaccine administered under India's Universal Immunization Programme in the context of measles-rubella elimination goal: A longitudinal study.

Background & objectives: There is a paucity of data regarding immunogenicity of recently introduced measles-rubella (MR) vaccine in Indian children, in which the first dose is administered below one year of age. This study was undertaken to assess the immunogenicity against rubella and measles 4-6 wk after one and two doses of MR vaccine administered under India's Universal Immunization Programme (UIP). Methods: In this longitudinal study, 100 consecutive healthy infants (9-12 months) of either gender attending the immunization clinic of a tertiary care government hospital affiliated to a medical college of Delhi for the first dose of routine MR vaccination were enrolled. MR vaccine (0.5 ml, subcutaneous) was administered to the enrolled participants (1st dose at 9-12 months and 2nd dose at 15-24 months). On each follow up (4-6 wk post-vaccination), 2 ml of venous blood sample was collected to estimate the antibody titres against measles and rubella using quantitative ELISA kits. Seroprotection (>10 IU/ml for measles and >10 WHO U/ml for rubella) and antibody titres were evaluated after each dose. Results: The seroprotection rate against rubella was 97.5 and 100 per cent and against measles was 88.7 per cent and 100 per cent 4-6 wk after the first and second doses, respectively. The mean (standard deviation) titres against rubella and measles increased significantly (P<0.001) after the second dose in comparison to the levels after the first dose by about 100 per cent and 20 per cent, respectively. Interpretation & conclusions: MR vaccine administered below one year of age under the UIP resulted in seroprotection against rubella and measles in a large majority of children. Furthermore, its second dose resulted in seroprotection of all children. The current MR vaccination strategy of two doses, out of which the first is to be given to infants below one year of age, appears robust and justifiable among Indian children.

Insights into Changing Dermatophyte Spectrum in India Through Analysis of Cumulative 161,245 Cases Between 1939 and 2021.

Dermatophytosis is one of the most common superficial infections of the skin affecting nearly one-fifth of the world population at any given time. With nearly 30% of worldwide terbinafine-resistance cases in Trichophyton mentagrophytes/Trichophyton interdigitale and Trichophyton rubrum reported from India in recent years, there is a significant burden of the emerging drug resistance epidemic on India. Here, we carry out a comprehensive retrospective analysis of dermatophytosis in India using 1038 research articles pertaining to 161,245 cases reported from 1939 to 2021. We find that dermatophytosis is prevalent in all parts of the country despite variable climatic conditions in different regions. Our results show T. rubrum as the most prevalent until 2015, with a sudden change in dermatophyte spectrum towards T. mentagrophytes/T. interdigitale complex since then. We also carried out an 18S rRNA-based phylogenetics and an average nucleotide identity-and single nucleotide polymorphism-based analysis of available whole genomes and find very high relatedness among the prevalent dermatophytes, suggesting geographic specificity. The comprehensive epidemiological and phylogenomics analysis of dermatophytosis in India over the last 80 years, presented here, would help in region-specific prevention, control and treatment of dermatophyte infections, especially considering the large number of emerging resistance cases.

Aetiology of hospital-acquired diarrhoea in under-five children from an urban hospital in East Delhi, India.

Background & objectives: Majority of the studies of hospital-acquired diarrhoea conducted in Western countries have focused on the detection of Clostridium difficile in stool samples. Limited Asian and Indian literature is available on hospital-acquired diarrhoea. This study was aimed to describe the aetiological profile for hospital-acquired diarrhoea in children aged below five years. Methods: One hundred children aged one month to five years who developed diarrhoea (≥3 loose stools for >12 h) after hospitalization for at least 72 h were enrolled. Children who were prescribed purgatives or undergoing procedures such as enema and endoscopy or those with underlying chronic gastrointestinal disorders such as celiac disease and inflammatory bowel disease were excluded from the study. Stool samples from the enrolled children were subjected to routine microscopic examination, modified Ziel-Nielson (ZN) staining for Cryptosporidium and culture for various enteropathogens. Multiplex PCR was used to identify the strains of diarrhoeagenic Escherichia coli. Rotavirus detection was done using rapid antigen kit. Toxins (A and B) of C. difficile were detected using enzyme immunoassay. Results: Of the 100 samples of hospital-acquired diarrhoea analysed, diarrhoeagenic E. coli (DEC) was found to be the most common organism, detected in 37 per cent of cases (enteropathogenic E. coli-18%, enterotoxigenic E. coli-8%, enteroaggregative E. coli-4% and mixed infections-7%). Cryptosporidium was detected in 10 per cent of cases. Rotavirus was detected in six per cent and C. difficile in four per cent of cases. Interpretation & conclusions: The findings of this study suggest that the aetiological profile of hospital-acquired diarrhoea appears to be similar to that of community-acquired diarrhoea, with DEC and Cryptosporidium being the most common causes. The efforts for the prevention and management of hospital-acquired diarrhoea should, thus, be directed towards these organisms.

Integron mediated antimicrobial resistance in diarrheagenic Escherichia coli in children: in vitro and in silico analysis.

The exchange of genes between bacterial chromosome and plasmid(s) and their integration into integrons are mainly responsible for acquisition and dissemination of antibiotic resistance. We investigated the role of integrons and their underlying molecular mechanisms leading to development of adaptability in E. coli and eventual resistance to antimicrobials. Escherichia coli isolates (n = 120); including 40 diarrheagenic isolates, an even number of isolates from cases other than diarrhea, and equal number of isolates from healthy children recovered from fresh stool samples were used for identification of integron genes and gene cassettes. The association of integrons with antibiotic resistance was assayed before phylogenetic analysis. DNA sequence analysis revealed class 1 and 2 integrons in 55.83% and 21.66% isolates, respectively. The integron presence was found significantly associated with the probability of antibiotic resistance in E. coli; the association being highest with class 1 integron. Modelling and molecular docking along with molecular dynamics simulation analyses found ceftriaxone and amoxicillin as potential inhibitors of dihydrofolate reductase (DHFR). The class 1 integrons of these pathogenic isolates can serve as prospective therapeutic targets using specific silencing strategies and combinational antimicrobial therapy. The findings may be useful for the development of a potent and versatile drug for DHFR inhibition.

"Azole menace"-An underappreciated trigger perpetuating the epidemic of antifungal therapeutic failure in cutaneous mycoses.

The South-Asian epidemic of anti-fungal therapeutic failures (AFTF) is on the rise. Although many demographic, environmental, and socioeconomic factors have been implicated in the genesis of this problem, two pharmacological issues warrant attention. While detailed discussions on the role of topical corticosteroid (TCS) in the changing landscape of the superficial mycotic infections in this region have been making headlines, another equally, rather more important pharmacological factor seems to have been undermined by the hype around TCS. The fastidious pharmacokinetic properties and related practical aspects of the triazole group of oral and topical antifungals, especially oral itraconazole seem to contribute significantly to the persistence of AFTF epidemic. In this paper, we shall discuss the broad aspects of the spectral precariousness of oral triazole antifungals with special emphasis to itraconazole, a concept known as the "azole menace" in the overall pathogenesis and tenacity of the AFTF epidemic.

Trichoscopy as a monitoring tool in assessing treatment response in 98 children with tinea capitis: A prospective clinical study.

Tinea capitis (TC) is the most common dermatophyte infection in children. Fungal culture the gold standard diagnostic method takes several weeks and has poor yields. Trichoscopy helps in rapid diagnosis and could work as a monitoring tool during antifungal therapy. Our main objective is to document the evolution of trichoscopic features with treatment and their correlation with clinical parameters in patients of TC. Forty-six and 52 children with clinically diagnosed TC that was confirmed by potassium hydroxide microscopy, received griseofulvin and terbinafine, respectively. Recruited children were subjected to clinical and trichoscopic assessment by calculation of CASS (clinical assessment severity score) and counting of TAHC (Total Altered hair count; negative and positive), respectively, at baseline and follow-up at 2, 4, and 6 weeks. McNemar, Wilcoxon singed ranked test and Spearman-rho correlation of various parameters was evaluated. Follow-up trichoscopy revealed significant (p < 0.009) disappearance of negative TAHC like black dot (second week onward), corkscrew, horseshoe and zigzag hair at 4 weeks and short broken hair, erythema telangiectasia hemorrhage (ETH) resolved at 6 weeks. Positive TAHC (regrowing hair) shows significant increase at 6 weeks (p < 0.001). CASS and negative TAHC showed significant difference at 4 weeks (p < 0.001) by analyzing boxplot graph. Therefore, trichoscopic resolution occurred before the clinical cure. Terbinafine subjects showed a higher clinical cure rate at 4 weeks (p = 0.02) as compared to griseofulvin. To conclude, trichoscopy is a good monitoring tool that could document the disappearance of almost all dystrophic hair at 4 to 6 weeks and is a more sensitive tool than microscopic examination. Regrowing hair and perifollicular scaling are markers of recovery.

Multilocus Sequence Typing of Clinical Isolates of Cryptococcus from India.

Cryptococcosis is a life-threatening infection caused by Cryptococcus neoformans and C. gattii species complex. In the present study, to understand the molecular epidemiology of 208 clinical isolates of Cryptococcus from different parts of India, multilocus sequence typing (MLST) using ISHAM MLST consensus scheme for C. neoformans/C. gattii species complex was used. MLST analysis yielded a total of 10 Sequence Types (STs)-7 STs for C. neoformans and 3 for C. gattii species complex. The majority of isolates identified as C. neoformans belonged to molecular type VNI with predominant STs 31 and 93. Only 3 isolates of C. gattii species complex were obtained, belonging to ST58 and ST215 of VGI and ST69 of VGIV. Phylogenetic analysis revealed less diversity among the clinical Indian isolates compared to the global MLST database. No association between prevalent STs and HIV status, geographical origin or minimum inhibitory concentration (MIC) could be established.

Acute Kidney Injury in Severe Preeclamptic Patients Admitted to Intensive Care Unit: Epidemiology and Role of Serum Neutrophil Gelatinase-associated Lipocalcin.

BACKGROUND: Patients with preeclampsia admitted to the intensive care unit (ICU) may have risk factors for acute kidney injury (AKI). Although the use of neutrophil gelatinase-associated lipocalcin (NGAL) to predict AKI is previously validated, we could locate only scanty data regarding the epidemiology of AKI and role of NGAL in preeclamptic patients admitted to ICU. METHODS: Patients with preeclampsia admitted to our ICU were included. The incidence and severity of AKI during the entire ICU stay were assessed using kidney disease improving global outcomes criteria, while the a priori risk factors and serum NGAL were also evaluated. RESULTS: A total of 52 preeclamptic patients admitted to ICU were included, among whom the majority had eclampsia (75%). AKI developed in 25 (48.1%) patients with stages 1, 2, and 3 in 56, 36, and 8%, respectively. The incidence of sepsis (16 vs 0%), shock (40 vs 7.4%), and anemia (84 vs 59.3%) was significantly greater in patients with AKI (p < 0.05). ICU mortality (28 vs 3.7%), duration of ICU, and hospital stay were significantly higher in patients who developed AKI (p < 0.05). There was no association of serum NGAL [274 (240-335) ng/mL] with AKI or the mortality (p = 0.725, 0.861); there was, however, a significant discriminatory value for eclampsia [p = 0.019; area under curve = 0.736 (95% confidence interval: 0.569-0.904)]. CONCLUSIONS: Although AKI is common among patients with preeclampsia admitted to ICU, serum NGAL does not predict its occurrence. HOW TO CITE THIS ARTICLE: Tyagi A, Yadav P, Salhotra R, Das S, Singh PK, Garg D. Acute Kidney Injury in Severe Preeclamptic Patients Admitted to Intensive Care Unit: Epidemiology and Role of Serum Neutrophil Gelatinase-associated Lipocalcin. Indian J Crit Care Med 2021;25(9):1013-1019.

The interplay among Th17 and T regulatory cells in the immune dysregulation of chronic dermatophytic infection.

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17  cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4+ T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research.

TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis.

BACKGROUND: T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. RESULTS: The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-ß levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. CONCLUSIONS: Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.

Procalcitonin Clearance, CD64, and HLA-DR as Predictors of Outcome in Febrile Neutropenic Children With Lymphoreticular Malignancies.

BACKGROUND: Febrile neutropenia (FN) is a dreaded complication of cancer chemotherapy. There has been a lot of improvement in supportive care in FN that has drastically reduced the infection-related mortality in these patients. The focus now is on reducing infection-related morbidity, healthcare costs and optimizing the quality of life of the child as well as their family during these episodes. In this study, biomarkers were studied as predictors of outcome so that outcome can be predicted earlier, and treatment modified accordingly. OBJECTIVE: To measure procalcitonin levels (at baseline and day 3), procalcitonin clearance, neutrophil CD64 expression levels (at baseline) and monocyte HLA-DR expression levels (at baseline), and their correlation with outcome. SETTING: Tertiary care hospital. STUDY TYPE: Cross-sectional observational study. POPULATION/PARTICIPANTS: Sixty-five episodes of FN in children below 12 years with lymphoreticular malignancies. Children receiving antibacterial and/or antifungal treatment within the last 7 days were excluded from the study. METHODS: The subjects recruited into the study had undergone complete clinical and laboratory evaluation as per hospital protocol. Procalcitonin (day 0 and 3), neutrophil CD64 expression, and monocytic HLA-DR expression levels were measured in these patients. RESULTS: Sixty-five episodes of FN were studied in children with lymphoreticular malignancy. It was found that procalcitonin and HLA-DR are very good markers of outcome, whereas CD64 although a good marker, was inferior to procalcitonin and HLA-DR in predicting outcome. Procalcitonin clearance was found to be superior to single value of procalcitonin. Furthermore, procalcitonin on day 3 was found to be a better predictor of outcome compared with its baseline value. Also, it was found that procalcitonin and HLA-DR had a significant correlation with baseline C-reactive protein levels. CONCLUSIONS: On the basis of the findings of the study we suggest that serial monitoring of procalcitonin levels be used in febrile neutropenic children with cancer. Procalcitonin levels on day 3 alone can be offered in resource poor setting. The role of HLA-DR and CD64 also seems promising and needs to be further explored in larger multicentric studies.

Aetiology and outcome of acute diarrhoea in children with severe acute malnutrition: a comparative study.

OBJECTIVE: To compare the microbiological profile, clinical course and outcome of acute diarrhoea in children aged <5 years having severe acute malnutrition (SAM) with those of children having normal nutritional status. DESIGN: Cross-sectional comparative study. SETTING: Tertiary-care hospital catering mainly to the urban poor of East Delhi, India. PARTICIPANTS: Children aged <5 years (n 140; seventy with SAM (cases) and seventy with normal anthropometry (controls)) with acute diarrhoea (duration < 14 d). Stool samples were collected for conventional culture, microscopy, acid-fast staining, rotavirus and Cryptosporidium antigen detection, and subtyping of diarrhoeagenic Escherichia coli (DEC). We followed-up these children for persistent diarrhoea and subsequent diarrhoeal episode in the next 3 months. RESULTS: Rotavirus was detected in six (9 %) cases and in fifteen (21 %) controls (P = 0·03; OR = 0·34; 95 % CI 0·12, 0·94). DEC was isolated significantly more in cases compared with controls (93 v. 64 %; P < 0·001; OR = 7·25; 95 % CI 2·57, 20·4). Cryptosporidium was detected in seven (10 %) cases and five (7 %) controls. Total duration of diarrhoea and percentage change in weight after resolution of diarrhoea were comparable between cases and controls. At 3-month follow-up, number of subsequent episodes of diarrhoea and persistent diarrhoea were comparable between the two groups. CONCLUSIONS: Rotavirus was found significantly less frequently, whereas DEC was detected more frequently in children with SAM in comparison to non-malnourished children. To further reduce diarrhoea-related mortality, preventive and therapeutic interventions need to be designed against organisms causing diarrhoea in children with SAM.

Clinico-mycological study of onychomycosis in a tertiary care hospital-A cross-sectional study.

Onychomycosis (OM), has a worldwide prevalence of 5% and 0.5%-5% in India. Trichophyton. rubrum (T rubrum) and T mentagrophytes are the most commonly isolated fungi. As the clinical and mycological characteristics change with time and geographical region; it is important to study the temporal and topographic patterns periodically. The study was conducted to identify the epidemiological and clinico-mycological characteristics of patients with OM attending a tertiary care hospital in Delhi. Hundred patients with clinical diagnosis of OM were recruited. Among these, 88 patients who tested positive for OM on direct microscopy with KOH, culture and/or histopathology with periodic acid-Schiff were included in the study. The clinico-mycological characteristics and risk factors associated with OM were evaluated. OM was more common in males (M:F = 2.5:1). The mean age of patients with OM was 39 ± 15.3 years (SE 1.52) with mean disease duration of 27.6 ± 46.1 months (SE 4.9). Seventeen (19.3%) patients had concomitant diabetes mellitus. The patients displayed mean body mass index (BMI) of 25.67 ± 1.35 kg/sq m. Concurrent dermatophytosis of skin was present in 35 (39.77%) patients. Two feet-one hand syndrome was present in 5 patients. Fingernail involvement without toenail involvement was more common than toenail involvement alone. (43.18% vs 38.63%). Distal and lateral subungual OM (DLSO) was the commonest clinical variant (81.8%). Mycological culture showed growth in 47 (53.40%) patients. Dermatophytes were isolated in majority, that is in 30 (63.82%) patients followed by non-dermatophytic moulds (NDM) in 7 (14.8%) and Candida spp. in the remaining 10 (21.27%) patients.

Characteristics, outcome and risk factors for mortality of paediatric patients with ICU-acquired candidemia in India: A multicentre prospective study.

BACKGROUND: The epidemiology, clinical profile and outcome of paediatric candidemia vary considerably by age, healthcare settings and prevalent Candida species. Despite these differences, few comprehensive studies are undertaken. This nationwide study addresses this knowledge gap. METHODS: 487 children who contracted ICU-acquired candidemia at 23 Indian tertiary care centres were assessed for 398 variables spanning demography, clinical characteristics, microbiology, treatment and outcome. RESULTS: Both neonates (5.0 days; range = 3.0-9.5) and non-neonatal children (7.0 days; range = 3.0-13.0) developed candidemia early after ICU admission. Majority of neonates were premature (63.7%) with low birthweight (57.1%). Perinatal asphyxia (7.3%), pneumonia (8.2%), congenital heart disease (8.4%) and invasive procedures were common comorbidities, and antibiotic use (94.1%) was widespread. C tropicalis (24.7%) and C albicans (20.7%) dominated both age groups. Antifungal treatment (66.5%) and removal of central catheters (44.8%) lagged behind. Overall resistance was low; however, emergence of resistant C krusei and C auris needs attention. The 30-day crude mortality was 27.8% (neonates) and 29.4% (non-neonates). Logistic regression identified admission to public sector ICUs (OR = 5.64), mechanical ventilation (OR = 2.82), corticosteroid therapy (OR = 8.89) and antifungal therapy (OR = 0.22) as independent predictors of 30-day crude mortality in neonates. Similarly, admission to public sector ICUs (OR = 3.62), mechanical ventilation (OR = 3.13), exposure to carbapenems (OR = 2.18) and azole antifungal therapy (OR = 0.48) were independent predictors for non-neonates. CONCLUSIONS: Our findings reveal a distinct epidemiology, including early infection with a different spectrum of Candida species, calling for appropriate intervention strategies to reduce candidemia morbidity and mortality. Independent factors identified in our regression models can help tackle these challenges.

Effect of Segmental Thoracic Epidural Block on Pancreatitisinduced Organ Dysfunction: A Preliminary Study.

BACKGROUND: This preliminary randomized controlled study evaluated effect of thoracic epidural block (TEB) on progression of acute pancreatitis induced organ dysfunction/failure. MATERIALS AND METHODS: Patients with predicted severe acute pancreatitis, without contraindication to TEB were randomized to receive (group TE) or not receive a TEB (group NTE) (n = 16 each). For group TE, TEB was performed at T8-9 or T9-10 vertebral level, with infusion of ropivacaine (0.2%) along with fentanyl 2 µg/mL; in group NTE, intravenous morphine was used instead, both interventions titrated to NRS of <4. SOFA score was assessed daily till discharge from ICU, and aggregate SOFA calculated by summing worst scores for each of organ system during ICU stay as primary outcome measure. Other surrogate measures of patient outcome were recorded as secondary objectives. RESULTS: Aggregate SOFA score was statistically similar between both groups (group NTE: 3 [2 - 4]; group TE: 5 [2 - 6]) (P = 0.379); but there was trend of improvement in SOFA score in group TE versus a worsening in group NTE. Duration of hospital stay, and number of patients requiring mechanical ventilation were statistically similar; mortality was insignificantly lesser for group TE (12.5% versus 6.6%; p = 1.000). Fall in serum procalcitonin was significantly greater for group TE. CONCLUSION: Thoracic epidural was associated with insignificant clinical trend towards better organ functions and lesser mortality; along with significantly greater fall in serum procalcitonin. These are encouraging results that could guide future use of thoracic epidural in acute pancreatitis for its non-analgesic benefits. HOW TO CITE THIS ARTICLE: Tyagi A, Gupta YR et al. Effect of Segmental Thoracic Epidural Block on Pancreatitis Induced Organ Dysfunction: A Preliminary Study. Indian J of Crit Care Med 2019;23(2):89-94.

Low tidal volume ventilation strategy and organ functions in patients with pre-existing systemic inflammatory response.

BACKGROUND AND AIMS: Ventilation can induce increase in inflammatory mediators that may contribute to systemic organ dysfunction. Ventilation-induced organ dysfunction is likely to be accentuated if there is a pre-existing systemic inflammatory response. MATERIAL AND METHODS: Adult patients suffering from intestinal perforation peritonitis-induced systemic inflammatory response syndrome and scheduled for emergency laparotomy were randomized to receive intraoperative ventilation with 10 ml.kg-1 tidal volume (Group H) versus lower tidal volume of 6 ml.kg-1 along with positive end-expiratory pressure (PEEP) of 10 cmH2O (Group L), (n = 45 each). The primary outcome was postoperative organ dysfunction evaluated using the aggregate Sepsis-related Organ Failure Assessment (SOFA) score. The secondary outcomes were, inflammatory mediators viz. interleukin-6, tumor necrosis factor-α, procalcitonin, and C-reactive protein, assessed prior to (basal) and 1 h after initiation of mechanical ventilation, and 18 h postoperatively. RESULTS: The aggregate SOFA score (3[1-3] vs. 1[1-3]); and that on the first postoperative day (2[1-3] vs. 1[0-3]) were higher for group L as compared to group H (P < 0.05). All inflammatory mediators were statistically similar between both groups at all time intervals (P > 0.05). CONCLUSIONS: Mechanical ventilation with low tidal volume of 6 ml/kg-1 along with PEEP of 10 cmH2O is associated with significantly worse postoperative organ functions as compared to high tidal volume of 10 ml.kg-1 in patients of perforation peritonitis-induced systemic inflammation undergoing emergency laparotomy.

FcɛR1α gene polymorphism shows association with high IgE and anti-FcɛR1α in Chronic Rhinosinusitis with Nasal Polyposis.

Despite large number of investigations, the etiology of chronic rhinosinusitis (CRS) remains unclear. Several factors are likely involved in its onset. The genetic susceptibility of IgE-responsiveness likely caused by polymorphism(s) in high affinity receptor for IgE (FcɛR1α) gene can help in understanding the pathophysiology of CRS with nasal polyposis (CRSwNP). A population-based case-control association analysis was conducted to assess the risk of CRSwNP conferred by single nucleotide polymorphisms (SNPs) in FcɛR1α gene in a North Indian cohort. Two promoter and three exonic regions of FcɛR1α gene were amplified and sequenced to investigate five SNPs: rs2427827, rs2251746, rs2298804, rs2298805, and rs2269718. BLAST analysis and subsequent multiple alignments, with known sequences available in the NCBI database, were performed. Total serum IgE and FcɛR1α antibody levels were estimated. Patient IgE level of 461.22 ± 436.43 in comparison to 83.62 ± 58.043 IU/mL in controls (P < 0.0001), and FcɛR1α antibody level of 292.38 ± 115.27 in comparison to 160.56 ± 105.9 in controls (P < 0.0001), depicts their highly significant associations with CRSwNP disease. However, no SNP showed evidence of association with CRSwNP; although relatively higher Odds ratios were observed with rs2427827, rs2251746, and rs2298804. Patient stratification revealed a significant association (P < 0.05) of rs2427827 SNP with high IgE level CRSwNP patients. Nonetheless, we found no SNP associated with low serum IgE level patients. SNP (rs2427827) in the FcɛR1α gene region and high IgE levels may confer susceptibility to CRSwNP in north Indian population. However, further studies including larger sample size, gene-gene, and gene-environment interactions are required for its elucidation.

Bioengineered intravaginal isolate of Lactobacillus plantarum expresses algal lectin scytovirin demonstrating anti-HIV-1 activity.

Efforts to develop preventatives against HIV infection through sexual route have identified, among many, algal lectins as the potent molecules for scaffolding HIV entry inhibition. Algal lectin scytovirin (SVN) from Scytonema varium, a cyanobacterium, has anti-HIV effects with the potential for use in sculpting HIV neutralization. We created a recombinant strain of human vaginal L. plantarum for extracellular expression of recombinant (r)SVN. The rSVN protein containing culture supernatant was analyzed for its binding with HIV-1 gp160, and for inhibiting infection with primary R5 and X4 HIV-1 strains in TZM-bl cells. The rSVN protein extant in recombinant L. plantarum culture supernatant binds to HIV-1 gp160 and reduces the HIV-induced cytopathic effect to nearly 56.67% and 86.47% in R5 and X4 HIV-1 infected TZM-bl cells, respectively. The fortified L. plantarum may be explored for its use as a live virucide in vaginal mucosa of high risk women to prevent HIV entry.

Cytomegalovirus aggravates the autoimmune phenomenon in systemic autoimmune diseases.

BACKGROUND: Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. METHODS: We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. RESULTS: We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. CONCLUSION: Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.