Elastography for Evaluation of Regression in Liver Fibrosis After Surgical Biliary Drainage for Benign Biliary Strictures: A Practical Possibility?

BACKGROUND: Hepatic fibrosis and secondary biliary cirrhosis are consequences of long-standing benign biliary strictures. Evidence on the reversibility of fibrosis after the repair is incongruous. METHODOLOGY: A prospective observational study on patients who underwent Roux-en-Y hepaticojejunostomy for benign biliary stricture. A liver biopsy was performed during repair and correlated with preoperative elastography. The improvement in liver functions and regression of fibrosis was compared with preoperative liver function tests and elastography. RESULTS: A Total of 47 patients [mean age-38.9 y (Range: 21 to 66)] with iatrogenic benign biliary stricture were included. A strong female preponderance was noted. High strictures (type III and IV) comprised 72.7% of the study group. The median interval (injury to repair) was 7 months (2 to 72 mo). The median duration of jaundice was 3 months (1 to 20 mo). Both factors had a significant correlation with the stage of fibrosis ( P =0.001 and P =0.03, respectively). Liver biopsy revealed stage I, II, III, and IV fibrosis in 26 (55.3%), 11 (23.4%), 2 (4.3%), and 2(4.3%), respectively. The remaining 6 (12.8%) had no fibrosis. The severity of fibrosis had a good correlation with preoperative liver stiffness measurement-value on FibroScan. Significant improvement in liver function tests (bilirubin-3.55±3.48 vs. 0.59±0.52; Albumin-3.85±0.61 vs. 4.14±0.37; ALP-507.66±300.65 vs. 167±132.07; P value 0.00) and regression of fibrosis (liver stiffness measurement; 10.42±5.91 vs. 5.85±3.01, P value 0.00) was observed after repair of the strictures. CONCLUSION: Improved biliary function and regression of liver fibrosis can be achieved with timely repair of benign biliary stricture and it is feasible to be evaluated using elastography.

Halotolerant Pseudomonas koreensis S4T10 mitigate salt and drought stress in Arabidopsis thaliana.

Salt and drought are documented among the most detrimental and persistent abiotic stresses for crop production. Here, we investigated the impact of Pseudomonas koreensis strain S4T10 on plant performance under salt and drought stress. Arabidopsis thaliana Col-0 wild type and atnced3 mutant plants were inoculated with P. koreensis or tap water and exposed to NaCl (100 mM) for five days and drought stress by withholding water for seven days. P. koreensis significantly enhanced plant biomass and photosynthetic pigments under salt and drought stress conditions. Moreover, P. koreensis activated the antioxidant defence by modulating glutathione (GSH), superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activities to scavenge the reactive oxygen species produced due to the stress. In addition, the application of P. koreensis upregulated the expression of genes associated with antioxidant responses, such as AtCAT1, AtCAT3, and AtSOD. Similarly, genes linked to salt stress, such as AtSOS1, AtSOS2, AtSOS3, AtNHX1, and AtHKT1, were also upregulated, affirming the positive role of P. koreensis S4T10 in streamlining the cellular influx and efflux transport systems during salt stress. Likewise, the PGPB inoculation was observed to regulate the expression of drought-responsive genes AtDREB2A, AtDREB2B, and ABA-responsive genes AtAO3, AtABA3 indicating that S4T10 enhanced drought tolerance via modulation of the ABA pathway. The results of this study affirm that P. koreensis S4T10 could be further developed as a biofertilizer to mitigate salt and drought stress at the same time.

Recurrent mutations in Refractory/Relapsed Diffuse Large B cell Lymphoma by targeted gene sequencing.

Introduction-Whole genome sequencing of diffuse large B-cell lymphoma [DLBCL] has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and methods- A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and nine eight cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results- A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.

Lean Indian patients with non-alcoholic fatty liver disease (NAFLD) have less metabolic risk factors but similar liver disease severity as non-lean patients with NAFLD.

INTRODUCTION: Although most patients with NAFLD are obese or overweight, some are lean with normal BMI. Our aim was to assess differences in clinicopathological profile and liver disease severity among lean and non-lean NAFLD. METHODS: Data of 1040 NAFLD patients over last 10 years was analysed. BMI < 23 kg/m2 categorised lean patients. Non-invasive assessment of steatosis was done by ultrasound and controlled attenuation parameter (CAP) while fibrosis was assessed with FIB-4 and liver stiffness measurement (LSM). FibroScan-AST (FAST) score was used for non-invasive prediction of NASH with significant fibrosis. Histology was reported using NASH-CRN system. RESULTS: 149 (14.3%) patients were lean while 891 (85.7%) patients were non-lean. Diabetes mellitus [25 (16.7%) vs 152 (17.05%), p > 0.99], elevated triglycerides [81 (54.3%) vs 525 (58.9%), p = 0.33] and low HDL [71(47.6%) vs 479(53.7%), p = 0.18] were observed in a similar proportion. Lean patients were less likely to have central obesity [72 (48.3%) vs 788 (88.4%), p < 0.001], hypertension [16 (10.7%) vs 239(26.8%), p < 0.001] and metabolic syndrome [21 (14.09%) vs 290 (32.5%), p < 0.001]. No difference in steatosis assessment was noted using ultrasound (p = 0.55) or CAP (0.11). FAST [0.38 (0.18-0.66) vs 0.39 (0.27-0.73), p = 0.53], FIB-4 [1.08 (0.65-1.91) vs 1.09 (0.66-1.94), p = 0.94] and LSM [6.1 (4.8-7.9) vs 6.2 (4.7-8.6), p = 0.19) were similar. Liver biopsy was available in 149 patients [lean: 19 (12.7%), non-lean: 130 (87.3%)]. There was no difference in the number of patients with NASH [4 (21.05%) vs 20 (15.3%), p = 0.51], significant fibrosis [2 (10.5%) vs 32 (24.6%), p = 0.25] or advanced fibrosis [1 (5.26%) vs 18 (13.84%), p = 0.47]. CONCLUSION: Although metabolic co-morbidities are less common, there is no difference in liver disease severity among both groups.

Placenta as a site of HEV replication and inflammatory cytokines modulating the immunopathogenesis of HEV in pregnant women.

Viral hepatitis E is an under-estimated clinical entity with high mortality (20%-30%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis/acute liver failure and positive for either HEV-immunoglobulin M (IgM)/HEV-RNA and 30 pregnant women negative for HEV RNA/IgM/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5 ml blood was collected from the mother for HEV-RNA. Replicative RNA and viral load in placental tissue were detected through Real-Time PCR. Placental tissues from the maternal/fetal sides were stained for HEV antigen using HEV-open reading frame-2 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)-1ß and IL-18 cytokine levels using Duo-R&D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL-1ß and IL-18 cytokine genes expression.Of the 10 HEV RNA-positive sera, 9 had HEV RNA either in the maternal/fetal side of the placenta with the mean viral load of 137.4 IU/ml. Of the 10 HEV RNA-positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL-1ß and IL-18 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31 ± 4.462 vs. 8.85 ± 4.36 pg/ml; p < 0.0001*** and 2275 ± 536.9 vs. 1085 ± 531.7 pg/ml; p < 0.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra-hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in HEV-infected pregnant women might be contributing to the HEV pathogenesis in pregnancy.

Development of a cost-effective ex vivo lung perfusion system for lung transplantation in India.

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs.

Spectrum of PIK3CA/AKT mutations across molecular subtypes of triple-negative breast cancer.

PURPOSE: The heterogeneity of triple-negative breast cancer (TNBC) confers variable response to chemotherapy that results in poor outcome and relapse. Due to lack of targeted therapy, there is a need to provide molecular classification of TNBC and identify probable therapeutic targets. METHODS: We classified TNBC into surrogate molecular subtypes by immunohistochemistry and evaluated hotspot mutations (N = 80) in PIK3CA (exon 4, 9, and 20) and AKT1 (exon 2) in TNBC subtypes by Sanger sequencing. RESULTS: TNBCs were classified into Basal-like 1(BL1) (n = 20, 25%), Mesenchymal (n = 19, 23.75%), Luminal Androgen (LAR) (n = 12, 15%), Basal+Mesenchymal (Mixed type) (n = 10, 12.5%), and unclassified subtype (n = 19, 23.75%). PIK3CA mutations were observed in 16.25% (13/80) TNBC cases. PIK3CA mutations were more frequent in exon 20 (8.7%) than in exon 9 (5%) and exon 4 (2.5%). PIK3CA mutations were frequent in LAR subtype (33.3%) followed by unclassified type (31.5%), Mesenchymal (10.5%), and BL1 (5%) subtypes. Two hotspot mutations were found in AKT1 (T21I, E17K) in mixed and unclassified subtype. CONCLUSIONS: This study highlights the heterogeneity within TNBCs. Higher frequencies of PIK3CA mutations were noted in LAR subtypes and unclassified type, comparable to their incidence reported in literature in ER-positive tumors. The mutation status can be used as potential biomarker for PI3K inhibitors in TNBC subgroups.

Acetic acid improves drought acclimation in soybean: an integrative response of photosynthesis, osmoregulation, mineral uptake and antioxidant defense.

Exposure to drought stress negatively affects plant productivity and consequently threatens global food security. As global climates change, identifying solutions to increase the resilience of plants to drought is increasingly important. Several chemical treatments have recently emerged as promising techniques for various individual and combined abiotic stresses. This study shows compelling evidence on how acetic acid application promotes drought acclimation responses in soybean by investigating several morphological, physiological and biochemical attributes. Foliar applications of acetic acid to drought-exposed soybean resulted in improvements in root biomass, leaf area, photosynthetic rate and water use efficiency; leading to improved growth performance. Drought-induced accumulation of reactive oxygen species, and the resultant increased levels of malondialdehyde and electrolyte leakage, were considerably reverted by acetic acid treatment. Acetic acid-sprayed plants suffered less oxidative stress due to the enhancement of antioxidant defense mechanisms, as evidenced by the increased activities of superoxide dismutase, ascorbate peroxidase, catalase, glutathione peroxidase and glutathione S-transferase. Improved shoot relative water content was also linked to the increased levels of soluble sugars and free amino acids, indicating a better osmotic adjustment following acetic acid treatment in drought-exposed plants. Acetic acid also increased stem/root, leaf/stem and leaf/root mineral ratios and improved overall mineral status in drought-stressed plants. Taken together, our results demonstrated that acetic acid treatment enabled soybean plants to positively regulate photosynthetic ability, water balance, mineral homeostasis and antioxidant responses; thereby suggesting acetic acid as a cost-effective and easily accessible chemical for the management of soybean growth and productivity in drought-prone areas.

Adaptive Mechanisms of Halophytes and Their Potential in Improving Salinity Tolerance in Plants.

Soil salinization, which is aggravated by climate change and inappropriate anthropogenic activities, has emerged as a serious environmental problem, threatening sustainable agriculture and future food security. Although there has been considerable progress in developing crop varieties by introducing salt tolerance-associated traits, most crop cultivars grown in saline soils still exhibit a decline in yield, necessitating the search for alternatives. Halophytes, with their intrinsic salt tolerance characteristics, are known to have great potential in rehabilitating salt-contaminated soils to support plant growth in saline soils by employing various strategies, including phytoremediation. In addition, the recent identification and characterization of salt tolerance-related genes encoding signaling components from halophytes, which are naturally grown under high salinity, have paved the way for the development of transgenic crops with improved salt tolerance. In this review, we aim to provide a comprehensive update on salinity-induced negative effects on soils and plants, including alterations of physicochemical properties in soils, and changes in physiological and biochemical processes and ion disparities in plants. We also review the physiological and biochemical adaptation strategies that help halophytes grow and survive in salinity-affected areas. Furthermore, we illustrate the halophyte-mediated phytoremediation process in salinity-affected areas, as well as their potential impacts on soil properties. Importantly, based on the recent findings on salt tolerance mechanisms in halophytes, we also comprehensively discuss the potential of improving salt tolerance in crop plants by introducing candidate genes related to antiporters, ion transporters, antioxidants, and defense proteins from halophytes for conserving sustainable agriculture in salinity-prone areas.

Fibular Strut Arthrodesis for Salvage of Campanacci Grade III Giant Cell Tumor of the Hallucal Proximal Phalanx: A Case Report.

Involvement of toe phalanges by giant cell tumor (GCT) is extremely rare; tumors in these locations tend to be aggressive. Whereas aggressive GCTs of the distal phalanx may be managed successfully by en-bloc resection without reconstruction or amputation, management of these lesions, when they involve the proximal phalanx, can be challenging. We present a Campannaci grade III GCT of the hallucal proximal phalanx in a 14-year old girl that had breached into the dorsal soft tissues and the metatarso-phalangeal joint. Wide local resection of the proximal phalanx along with reconstruction arthrodesis with an autologous, non-vascularized fibular strut graft was performed. There was no recurrence at 3 years of follow-up. The patient had an excellent functional outcome. To the best of our knowledge, this is the first case reporting the outcomes of fibular strut arthrodesis for salvage of GCT of the hallucal proximal phalanx.

Role of Oncofetal Protein CR-1 as a Potential Tumor Marker for Oral Squamous Cell Carcinoma.

Cripto-1 (CR-1) is an oncofetal protein with its role as a key factor in early process of carcinoma has been evaluated in cases of various cancers. However, very few studies have reported its role in oral cancer, which is the sixth most common cancer around the world, particularly with high prevalence in developing countries. Oral squamous cell carcinoma (OSCC) is the most predominant (90%) of all the histological types of oral cancer. Late detection, associated with increased morbidity and mortality, is mainly attributed to non-availability of a suitable biomarker for the disease. In the present pilot study, we have evaluated the role of soluble CR-1, in serum as a potential tumor marker for OSCC. CR-1 was estimated using sandwich ELISA in serum samples of 50 biopsy proven OSCC patients (pre and post treatment) along with age and gender matched healthy controls. Immunohistochemistry was also done in corresponding tumor tissue sections to check the expression of CR-1. Pre-treatment CR-1 was found to be 2.25-fold higher in serum of OSCC patients as compared to control (p < 0.0001***), which was reduced to 1.6 folds post treatment (p = 0.0006***). CR-1 levels were comparatively higher in early stage of disease. Upon IHC 80% of the cases were found to be positive for CR-1. This study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.

Acetic acid improves drought acclimation in soybean: an integrative response of photosynthesis, osmoregulation, mineral uptake and antioxidant defense.

Because of a production error, this article was published online before peer review was complete. The content has been removed pending the outcome of the peer review process. The publisher apologises for the error. This article is protected by copyright. All rights reserved.

Phenotype-Genotype Correlation of North Indian Progressive Familial Intrahepatic Cholestasis type2 Children Shows p.Val444Ala and p.Asn591Ser Variants and Retained BSEP Expression.

Backgrounds and Aims: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by a defect or deficiency of bile salt export protein (BSEP) due to mutation in the ABCB11 gene. We intend to evaluate the phenotype-genotype correlation in 10 diagnosed cases of PFIC2 in a single tertiary care center in North India. Methods: The clinical, biochemical, histopathological, immunohistochemical, ultrastructural and genetic data of the 10 diagnosed cases of PFIC2 were recorded. Results: Icterus, pruritus and bleeding manifestations were the commonest clinical symptoms. Giant cell transformation was seen in 50% of the patients. Two predominant genetic variants were ABCB11 missense p.Val444Ala (c. 1331 T > C) and ABCB11 missense p.Asn591Ser (c. 1772 A > G) in their homozygous or compound heterozygous states and were associated with retained BSEP immunopositivity and reduced but retained BSEP immunopositivity respectively. Conclusion: Retention of BSEP is common in North Indian children of PFIC2 with no phenotype-genotype correlation.

A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment.

Mucormycosis due to Mucorales is reported at large numbers in uncontrolled diabetics across India, but systematic multicenter epidemiological study has not been published yet. The present prospective study was conducted at four major tertiary care centers of India (two in north and two in south India) during 2013-2015 to compare the epidemiology, treatment strategies and outcome of mucormycosis between the two regions. Molecular techniques were employed to confirm the identity of the isolates or to identify the agent in biopsy samples. A total of 388 proven/probable mucormycosis cases were reported during the study period with overall mortality at 46.7%. Uncontrolled diabetes (n = 172, 56.8%) and trauma (n = 31, 10.2%) were the common risk factors. Overall, Rhizopus arrhizus (n = 124, 51.9%) was the predominant agent identified, followed by Rhizopus microsporus (n = 30, 12.6%), Apophysomyces variabilis (n = 22, 9.2%) and Rhizopus homothallicus (n = 6, 2.5%). On multivariate analysis, the mortality was significantly associated with gastrointestinal (OR: 18.70, P = .005) and pulmonary infections (OR: 3.03, P = .015). While comparing the two regions, majority (82.7%) cases were recorded from north India; uncontrolled diabetes (n = 157, P = .0001) and post-tubercular mucormycosis (n = 21, P = .006) were significantly associated with north Indian cases. No significant difference was noted among the species of Mucorales identified and treatment strategies between the two regions. The mortality rate was significantly higher in north Indian patients (50.5%) compared to 32.1% in south India (P = .016). The study highlights higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease.

Association of rno-miR-183-96-182 cluster with diethyinitrosamine induced liver fibrosis in Wistar rats.

Chronic liver injury due to various etiological factors including environmental carcinogens results in development of liver fibrosis. Numerous studies showed role of miRNAs in liver fibrosis. In the present study, we determined the rno-miR-183-96-182 cluster expression during hepatic fibrosis induced by diethylnitrosamine (DEN) treated Wistar rats and its association with plasma levels of circulating rno-miR-96, rno-miR-182, rno-miR-183, liver function test and lipid profile, aiming to identify their potential for histological stratification and early diagnosis of liver fibrosis. We found significant upregulation in the hepatic expression of rno-miR-183-96-182 cluster upon development of fibrosis in a DEN treated rats. Interestingly, the hepatic expression of this miRNA cluster correlates positively with the progression of fibrosis. Univariate analysis showed that hepatic expression of rno-miR-182-5p and rno-miR-183-5p and plasma activity of ALT are significant predictors of fibrosis. Multivariate logistic regression analysis revealed a panel of rno-miR-182-5p and ALT that can discriminate F2-F3 from F0-F1 (AUC = 0.87; P-value < 0.001), F4-F5-F6 from F0 to F1 (AUC = 0.981; P-value < 0.001), and F4-F5-F6 from F2 to F3 (AUC = 0.824; P-value < 0.001). A significant positive correlation of rno-miR-183-96-182 cluster members was also observed with plasma activities of ALT, AST, ALP, and levels of total cholesterol, HDLc and LDLc during fibrosis progression in DEN treated Wistar rats. Thus, it can be concluded that rno-miR-183-96-182 cluster being significantly up regulated and associated with chronic liver disease might play a role in fibrosis maintenance and progression. A panel of rno-miR-182-5p and ALT being significant predictors of fibrosis might improve histological stratification of fibrosis staging.

Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott-Aldrich syndrome.

Patients with Wiskott-Aldrich syndrome (WAS) are predisposed to malignancy and autoimmunity in addition to infections. We report a male child with WAS, who had presented with recurrent pneumonia, eczema, thrombocytopenia, autoimmune hemolytic anemia, and vasculitic skin lesions. Genetic analysis revealed a classical genotype WAS 155C>T; R41X. At 2 years of follow-up, he developed persistent headache and progressive hepatomegaly. Brain imaging showed a mass in the right frontal region, which on histopathology was shown to be high-grade non-Hodgkin lymphoma. Magnetic resonance cholangiopancreatography showed features of sclerosing cholangitis. This report extends the clinical spectrum and highlights unusual manifestations of sclerosing cholangitis and intracranial lymphoma in a patient with WAS.

Acquired TEF in Hodgkin Lymphoma in a Child: A Rare Clinical Association.

BACKGROUND: Malignancy is the most common etiology of acquired fistulae between the tracheobronchial tree and esophagus. The majority are due to either primary bronchial or esophageal carcinoma, and are typically observed in adult population. The occurrence of tracheoesophageal fistula (TEF) in patients with Hodgkin lymphoma is a rare phenomenon. OBSERVATION: We report a rare case of Hodgkin lymphoma with TEF in a 10-year-old girl at presentation. She also developed pulmonary tuberculosis later during the follow up. She was fed through a nasogastric tube to avoid aspiration through the fistulous tract. She did well with chemotherapy and anti-tubercular therapy. CONCLUSIONS: Our case suggests TEF in Hodgkin lymphoma at the time of diagnosis is a rare complication in pediatric age group. Lymphoma-related TEF require far less active intervention, as against esophageal or bronchial malignancy related TEF.

Malignancies in Children with Human Immunodeficiency Virus Infection - Our Experience at Chandigarh, North India.

Background: With improved survival in children living with human immunodeficiency virus (HIV) infection (CLHIV), malignancies are being increasingly recognized. Patients and methods: Among the CLHIV registered at our institute from January 1994 to March 2015, children with malignancy were analysed in detail. Results: In total, 734 children affected by HIV were registered. Out of these, 11 children (9 boys, 2 girls) were diagnosed to have malignancy. Malignancy was the presenting feature of HIV infection in 4 children. High-grade non-Hodgkin lymphoma (NHL) was the most common malignancy noted in 9 of 11 (81%) children, whereas the remaining 2 children had Hodgkin's lymphoma. Survival in our cohort was 80% among children in whom chemotherapy was initiated, and overall survival was 36% (4 of 11 children). Conclusion: NHL was the most common malignancy in CLHIV in our cohort. Low-conditioning chemotherapy protocols along with initiation of anti-retroviral therapy resulted in improved outcomes in CLHIV with malignancy.

Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial. There is sparse literature on the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor (TLR) signaling in NAFLD. The present study evaluated the relationship of SIBO with expression of TLR signaling genes in patients with NAFLD. METHODS: A total of 142 subjects composed of NAFLD (n = 60, mean age 38.7 ± 10.4 years), chronic viral hepatitis (CVH) (n = 32, mean age 39.5 ± 10.6 years), and healthy volunteers (n = 50, mean age 36.56 ± 4.2 years) were enrolled in the study. Duodenal fluid was taken endoscopically in 32 prospective patients with NAFLD for evaluation of SIBO. Hepatic mRNA expression of TLR4, CD14, TLR2, NF-κß, and MD2 and protein expression of TLR4 and TLR2 were studied in 64 patients (NAFLD = 32, CVH = 32) by RT-PCR and immunohistochemistry, respectively. Serum levels of TNF-α, adiponectin, insulin, and endotoxins were also evaluated. RESULTS: Small intestinal bacterial overgrowth was present in 12 (37.5%) out of 32 patients with NAFLD with Escherichia coli as the predominant bacterium. In comparison with those without SIBO, patients with SIBO had significantly higher endotoxin levels and higher CD14 mRNA, nuclear factor kappa beta mRNA, and TLR4 protein expression. Patients with NASH had significantly higher endotoxin levels and higher intensity of TLR4 protein expression in comparison with patients without NASH. Serum levels of TNF-α, endotoxins, and insulin were significantly higher and of adiponectin lower in NAFLD in comparison with CVH and healthy volunteers. CONCLUSIONS: Our study provides the first direct evidence of role of SIBO and endotoxemia and its relation with TLR signaling genes and liver histology in patients with NAFLD.

A Rare Coexistence of Bilateral Congenital Wilms Tumor with Ductal Plate Malformation at Autopsy.

Congenital Wilms tumor is a tumor of childhood. Here we present an unusual case of bilateral congenital Wilms tumor with associated ductal plate malformation. In addition, there was also associated oligohydramnios, pulmonary hypoplasia, and multiple skeletal anomalies in this index case. Although various syndromic associations of Wilms tumor are well described in the literature, an association of congenital Wilms tumor with ductal plate malformation, polysplenia, and skeletal malformations is not reported. We believe that this is the first reported case of such an association.