Effect of Combined Low Dose Human Gonadotropic Hormone , Follicle Stimulating Hormone, and Testosterone Therapy (LFT Regimen) Versus Conventional High Dose Human Gonadotropic Hormone and Follicle Stimulating Hormone on Spermatogenesis and Biomarkers in Men With Hypogonadotropic Hypogonadism.

OBJECTIVE: In male congenital hypogonadotropic hypogonadism (CHH), it was observed that lower dose human gonadotropic hormone (hCG) can maintain normal intratesticular testosterone levels. We propose this study to compare the low-dose hCG, follicle stimulating hormone (FSH), and Testosterone (T) [LFT Regimen] to conventional treatment to induce virilization and fertility. DESIGN: This open-label randomized pilot study was conducted from June 2020 to December 2021. SUBJECTS AND OUTCOME MEASURES: CHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH (150U thrice per week), and T(100 mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce anti-mullerian hormone (AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups. RESULTS: Out of 30 patients, 23 (76·7%) subjects achieved spermatogenesis, and the median time was 12 (9-14·9) months. There was no difference in achieving spermatogenesis between the two groups (64·3% vs 7·5%,P = 0·204), and even the median time for spermatogenesis was similar (15months vs 12months,P = 0·248). Both groups had nonsignificant median plasma AMH at spermatogenesis, [6·6 ng/ml (3·3-9·76) vs4·41 ng/ml (2·3-6·47), P = 0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable [152·4 pg/ml (101·7-198·0) vs49·1 pg/ml (128·7-237·3), P = 0·488]. CONCLUSIONS: A reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

High frequency of memory stem cells with a distinct gene signature in HIV patients with treatment interruption.

Reservoirs of HIV remain a major obstacle to the complete eradication of virus despite regular anti-retroviral therapy (ART). Memory stem cells (Tscm), one of the major reservoirs, are relatively less studied owing to their presence in lower numbers and inaccessible anatomical locations. We have evaluated the molecular characteristics of Tscms in patients with ART interruption (n = 15) versus patients on uninterrupted ART (n = 12) using flow cytometry. RNA sequencing was done in the sorted Tscms to study the differential gene expression. Patients with ART interruption had significantly lower baseline CD4+T-cell counts and high viral loads as compared to patients on ART. The former group had significantly higher frequency of CD4+ and CD8+Tscms with a higher expression of PD-1 on CD8+Tscms. The transcriptome profile of Tscm was significantly different among the patient groups. The main pathways were cellular and metabolic pathways, cellular development pathways, cell differentiation and negative regulation of cellular migratory pathways. An increased yet dysfunctional CD8+ memory stem cells describe HIV-1-infected patients with break-in ART and a distinct transcriptional signature of CD4+ Tscm as compared to those of patients on ART. A more detailed understanding of the biology and dynamics of Tscm in future studies is warranted. Strategies to improve the functionality of the CD8+ Tscm will help these patients to tackle the outburst of viral replication that occurs after the cessation of therapy.

[68Ga]Ga-Pentixafor PET/CT imaging for in vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: correlation with quantitative receptors' density by immunochemistry techniques.

PURPOSE: In vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using [68Ga]Ga-Pentixafor PET/CT and to study correlation with quantitative CXCR4 receptors' tissue density by immunochemistry analyses. METHODS: [68Ga]Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77 M: 17F, mean age 60.1 ± 10.1 years) LC patients. CXCR4 receptors' expression on lung mass in all the patients was estimated by immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS) analyses. SUVmax on PET, intensity score on IHC, and mean fluorescence index (MFI) on FACS analyses were measured. RESULTS: A total of 75/94 (79.8%) cases had non-small cell lung cancer (NSCLC), 14 (14.9%) had small cell lung cancer (SCLC), and 5 (5.3%) had lung neuroendocrine neoplasm (NEN). All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.3 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to those in NSCLC and lung NEN. The mean SUVmax in adenocarcinoma (n = 16) was 8.0 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.1) and in not-otherwise specified (NOS) sub-types (n = 5; 5.8 ± 1.5) of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC adenocarcinoma (r = 0.538, p = 0.031) which supports the specific in vivo uptake of [68Ga]Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NEN (r = 0.747, p = 0.147) which may be due to the small sample size. [68Ga]Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cutoff SUVmax = 7.2). This technique presented similar sensitivity (87.5%) and specificity (71.4%) (ROC cutoff SUVmax = 6.7) for differentiating adenocarcinoma and squamous cell variants of NSCLC. CONCLUSION: The high sensitivity and specificity of [68Ga]Ga-Pentixafor PET/CT for in vivo targeting of CXCR4 receptors in lung cancer can thus be used effectively for the response assessment and development of CXCR4-based radioligand therapies in LC.

Natural history and profile of selective cytokines in patients of acute pancreatitis with acute kidney injury.

OBJECTIVES: To study the natural course of patients with acute pancreatitis (AP) with acute kidney injury (AKI) and their cytokine profile. METHODS: Natural course of patients with AP and AKI was studied in 97 individuals. Levels of TNFα, IL-6, IL-10, IL-8 and IL-1ß were measured at presentation and at 72 h in patients who developed AKI. RESULTS: Amongst the entire cohort, 16.4% patients developed AKI (persistent AKI - 11 patients, transient AKI - 5 patients). Mortality rate was 25% amongst patients with AKI. Levels of IL-6 (p = 0.035) and IL-8 (p = 0.002) were found to be significantly higher in the AKI group. On multivariate analysis, IL-8 levels at baseline were found to be an independent predictor of AKI. AKI group had significant rise of TNF-α (P < 0.001), IL-6 (P < 0.001) and IL- 1ß (P < 0.001) on day 3 whereas persistent-AKI group had significant rise of TNF-α (p = 0.031), IL-6 (p = 0.001) and IL-1ß on day 3 and significant decline of IL-10 (p = 0.015). Using a cut-off of 105 pg/ml, IL-8 levels at baseline could predict AKI with a sensitivity of 87.5% and specificity of 59.2%, with area under the curve being 0.744 (p = 0.002). CONCLUSION: AP patients developing AKI have poor prognosis. IL-8 levels can predict AKI in patients with AP.

A juggernaut of innate & adaptive immune cells in chronic hepatitis C.

Hepatitis C virus (HCV) is a small positive-sense, single-stranded RNA virus, the causal organism for chronic hepatitis. Chronic hepatitis leads to inflammation of liver, causing cirrhosis, fibrosis and steatosis, which may ultimately lead to liver cancer in a few cases. Innate and adaptive immune responses play an important role in the pathogenesis of HCV infection, thus acting as an important component in deciding the fate of the disease. Numerous studies have indicated that the derangement of these immune responses results in the persistence of infection leading to chronic state of the disease. Interactions between virus and host immune system generally result in the elimination of virus, but as the virus evolves with different evading mechanisms, it makes environment favourable for its survival and replication. It has been reported that HCV impairs the immune system by functional modulation of the cells of innate as well as adaptive immune responses, resulting in chronic state of the disease, influencing the response to antiviral therapy in these patients. These defects in the immune system lead to suboptimal immune responses and therefore, impaired effector functions. This review highlights the involvement or association of different immune cells such as natural killer cells, B cells, dendritic cells and T cells in HCV infection and how the virus plays a role in manipulating certain regulatory mechanisms to make these cells dysfunctional for its own persistence and survival.

Immunological markers for identifying recent HIV infection in North-West India.

Background & objectives: Being more efficient and widely used, limiting antigen (LAg)-avidity enzyme immunoassay (EIA) based on the recent infection testing algorithm (RITA) has been developed for differentiating recent and established HIV-1 infection. So far, LAg-avidity EIA has not been validated among the Indian population. Hence, the present study was planned to identify recent HIV infections in high risk patients in the North-West region of India using modified LAg-avidity RITA. Methods: Four hundred HIV-positive high risk patients registered on pre-antiretroviral therapy (ART) programme in the last one year, from five ART centres in North-Western States of India, were included for identifying the recent HIV infections. One hundred HIV-positive cases registered for pre-ART for greater than two years in ART centres were included for estimating false recent rate (FRR). Single-well LAg-avidity EIA-based modified RITA was used to identify recent HIV infection cases. Results: Of the 400 HIV-1-positive samples, 64 (16%) were found to have been infected within the past 130 days. The proportion of recent HIV infections was 16.8 per cent (18/107) among female sex workers, 10.7 per cent (9/84) among men who have sex with men and 17.7 per cent (37/209) among injecting drug users. The FRR was one per cent (1/100). Interpretation & conclusions: LAg-avidity EIA-based modified RITA provided good discrimination between recent and non-recent HIV infection, hence, it could be considered suitable for estimating HIV incidence in sentinel surveillance system in India.

Oral Nano Vitamin D Supplementation Reduces Disease Activity in Ulcerative Colitis: A Double-Blind Randomized Parallel Group Placebo-controlled Trial.

INTRODUCTION: Vitamin D possesses anti-inflammatory properties and could be beneficial in ulcerative colitis (UC). METHODS: We studied the effect of oral nano vitamin D3 supplementation on disease activity in active UC [ulcerative colitis disease activity index (UCDAI)≥3]. Patients with active UC and vitamin D <40 ng/mL were randomized to receive either oral nano vitamin D (60,000 IU/d×8 d) or placebo. They were evaluated for disease activity (UCDAI scores, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin) at baseline and reassessed at 4 weeks. The response was defined as a 3-point reduction in UCDAI score at 4 weeks and reduction in inflammatory markers. RESULTS: The median vitamin D levels increased from 15.4 to 40.83 mg/dL in vitamin D group (P≤0.001) and marginally from 13.45 to 18.85 mg/dL (P=0.027) in controls. The 3-point reduction in UCDAI was seen more often in vitamin D group as compared with the control (53% vs. 13%; P=0.001). Increase in vitamin D levels correlated with reduction in UCDAI score (P≤0.001; ρ=-0.713), C-reactive protein (P≤0.001; ρ=-0.603), and calprotectin (P=0.004; ρ=-0.368). Patients who achieved target vitamin D of >40 ng/mL (n=17) more often had a 3-point reduction in UCDAI (80% vs. 20%; P≤0.001) and reduction in grade of severity from 60% to 35% (P=0.038). Vitamin D administration (odds ratio, 9.17; 95% confidence interval, 2.02-41.67) and baseline histologic activity (odds ratio, 1.92; 95% confidence intervals, 1.2-3.08) independently predicted response. CONCLUSIONS: Oral nano vitamin D supplementation in active UC is associated with a reduction in disease activity and severity grade and is seen more often in those who achieved a target vitamin D level of 40 ng/mL.

Cytokine profile in prediction of acute lung injury in patients with acute pancreatitis.

OBJECTIVES: To study the role of cytokines in prediction of acute lung injury (ALI) in acute pancreatitis. METHODS: Levels of TNFα, IL-6, IL-10, IL-8 and IL-1ß were measured in 107 patients at presentation and at 72 h in patients who developed acute lung injury. A model was devised to predict development of ALI using cytokine levels and SIRS score. RESULTS: The levels of TNF α (p < 0.0001), IL-6 (p < 0.0001), IL-8 (p < 0.0001) and IL-1ß (p < 0.0001) were significantly higher in the ALI group. IL-10 levels were significantly lower in persistent ALI (p-ALI) than in transient ALI (t-ALI) patients (p < 0.038). p-ALI group had significant rise of TNFα (p = 0.019) and IL-1ß (p = 0.001) while t-ALI group had significant rise of only IL-1ß (p = 0.044) on day 3 vs day 1. Combined values of IL-6 and IL-8 above 251 pg/ml had sensitivity of 90.9% and a specificity of 100% to predict future development of ALI. Composite marker-I (IL6 ≥ 80 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 98% whereas composite marker-II (IL8 ≥ 100 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 95% to predict future ALI. CONCLUSIONS: IL-6 and IL-8 can predict future development of ALI. When they are combined with SIRS, they can be used as comprehensive composite markers.

Cytomegalovirus Disease in HIV-infected Children-A Single-Centre Clinical Experience over 23 Years.

BACKGROUND: Cytomegalovirus (CMV) results in significant morbidity and mortality in Human Immunodeficiency Virus (HIV)-infected individuals. There is paucity of literature on paediatric CMV disease, especially from developing countries. METHODS: A retrospective review of records of all HIV-infected children with evidence of CMV disease was done. RESULTS: A total of 15 children were found to have CMV disease (retinitis in all, pneumonia in two and invasive gastrointestinal disease in one). Median CD4+ T cell count and percentage at diagnosis of CMV disease was 64.5 cells/µl and 3.6%, respectively. Intravenous ganciclovir was used in patients with active CMV disease. Of the 15 children, three died while two were lost to follow-up. Symptomatic patients had poor visual outcome and almost all children who were diagnosed on active screening attained normal vision. CONCLUSION: Retinitis is the most common CMV disease in HIV-infected children. Early detection by active screening and initiation of systemic ganciclovir reduces the morbidity.

Increased expression of negative regulators of cytokine signaling during chronic HIV disease cause functionally exhausted state of dendritic cells.

Mechanisms of functional impairment of dendritic cells (DCs) during chronic HIV-1 infection are not well understood. In order to understand this phenomenon, we aimed to study the expression of negative regulators of cytokine signaling and correlate with DC exhaustion during chronic HIV-1 disease. Monocyte-derived DCs (mo-DCs) from 27 HIV-1 infected patients (CD4+ T-cell counts: 429±44 cells/µL, plasma viral load: Log103.9±1.0copies/ml) and 19 healthy controls (HCs) were stimulated ex vivo with TLR4 agonist, lipopolysaccharide (LPS) for 2days to evaluate their functional fitness. The expression of a set of genes associated with cytokine signaling was evaluated in a custom designed PCR array by Real-Time PCR. The mo-DCs from HIV-1 infected patients depicted functional exhaustion as evident by decreased allo-stimulation index (mean±SD: 10±6 vs. 24±16) (p<0.05), decreased cytokine production (pg/ml) (IL-12: 4.6±16 vs. 25±85; TNF-α: 128±279 vs. 286±544; IL-10: 6±12 vs. 13±20; IL-8: 10,688±11,748 vs. 17,470±125,049) and retained endocytosis (1.1±0.3 vs. 1.0±0.29) (p<0.05) even after LPS-stimulation, as compared to HCs. Significantly upregulated expression of SOCS-1 (mean±SD fold change: 2.2±2vs.0.8±0.6), SOCS-3 (6.3±7.4vs.1.4±0.4), PIAS-1 (1.6±0.1vs.1.0±0.3) and SHP-1 (0.8±0.4vs.0.4±0.2) correlated positively with PD-L1 expression in these DCs (Spearman's coefficient, SOCS-1: 0.63, SOCS-3: 1.0 and PIAS-1: 0.7) (p<0.05). The expression of these molecules trended positively with plasma viral load and negatively with CD4+ T-cell counts. These findings suggest that the upregulation of negative regulatory factors during chronic HIV disease have profound down-modulatory effects on DC functions and establishment of an overall exhausted state. Understanding mechanisms causing upregulation of these factors may lead to the design of new generation therapeutics based on silencing of their gene expression.

Combination of low producer AA-genotypes in IFN-γ and IL-10 genes makes a high risk genetic variant for HIV disease progression.

Rate of HIV disease progression varies considerably among individuals, host genetic makeup be one of the possible reasons. We aimed to determine association of functional single nucleotide polymorphism (SNPs), (-179G/T and +874T/A) in IFN-γ and (-1082A/G, -819C/T and -592C/A) in IL-10 genes, with the rate of disease progression or susceptibility to HIV infection. Therapy naïve HIV infected individuals from North India, categorized as slow progressors or fast progressors and HIV exposed seronegative individuals were recruited for this study. Genotyping results revealed significantly higher frequencies of low producer AA genotype at +874T/A in IFN-γ gene and -592C/A position in IL-10 gene in FPs (p<0.002). Multifactor dimensional reduction (MDR) analysis revealed this to be a high risk combination for faster disease progression in HIV-1 infected individuals. Low producer AA genotype carriers at +874T/A in IFN-γ gene produced significantly low amounts of cellular IFN-γ. Low producing haplotype 'ATA' at -1082, -819 and -592 loci in IL-10 gene was significantly over-represented in FPs as compared to SPs (p<0.01) and these individuals showed poor response to therapy in terms of CD4 count gains after one year of ART, compared to high producing haplotype (GCC) carriers. Thus, a combination of genetic variations in IFN-γ and IL-10 cytokine genes in a single host associate with HIV disease progression and may help clinicians to better manage the HIV disease if known earlier.

Preproinsulin specific CD8+ T cells in subjects with latent autoimmune diabetes show lower frequency and different pathophysiological characteristics than those with type 1 diabetes.

Latent autoimmune diabetes in adults (LADA) resembles type 1 diabetes (T1D) in disease presentation except that its onset is slow. We compared pathophysiological characteristics of CD8+ T cells recognizing preproinsulin (PPI) derived epitopes in both disease groups using MHC-I dextramers (DMRs) in peripheral blood and after in-vitro stimulation with PPI. Subjects with T1D harbored higher frequency of DMR+ CD8+ T cells with relatively higher frequency of effector T cell subsets. Following stimulation with PPI, an increase in DMR+ CD8+ T cells, particularly the central-memory subset was observed in T1D group, whereas no significant change in DMR+ CD8+ T cell subsets was observed in LADA group. Intracellular expression of Granzyme-B and Perforin in DMR+ CD8+ T cells was comparable in both the groups. In conclusion, lower frequency and inferior proliferative potential on account of a relatively restrained central-memory subset of PPI specific CD8+ T cells are associated with slow rate of disease progression in LADA.

Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients.

Hepatitis B virus (HBV) cccDNA levels is an absolute marker of HBV replication in the liver of HBV infected patients. This study aimed to quantify the HBV cccDNA levels in sera and liver tissue samples of treatment naïve patients with chronic hepatitis B. Eighty one chronic hepatitis B (CHB) treatment naïve patients were enrolled from January 2009 to June 2011. Total HBV DNA and HBV cccDNA levels were quantified using sensitive real time PCR assay. The mean age of recruited patients was 34 ± 11.5 years. Fifty four (66.7%) patients were HBeAg negative. Liver tissue samples were available from 2 HBeAg positive and 21 HBeAg negative CHB patients. The amount of total intrahepatic HBV DNA ranged from 0.09 to 1508.92 copies/cell. The median intrahepatic HBV cccDNA was 0.31 and 0.20 copies/cell in HBeAg positive and HBeAg negative cases, respectively. Serum HBV cccDNA was detectable in 85.2 % HBeAg positive and 48.1% HBeAg negative CHB patients. Median serum HBV cccDNA was 46,000 and 26,350 copies/mL in HBeAg positive and HBeAg negative subjects, respectively. There was a significant positive correlation between the levels of intrahepatic total HBV DNA and intrahepatic HBV cccDNA (r = 0.533, p = 0.009). A positive correlation was also seen between serum HBV cccDNA levels and serum HBV DNA levels (r = 0.871, p < 0.001). It was concluded that serum HBV cccDNA could be detectable in higher proportion of HBeAg positive patients compared to HBeAg negative patients. Moreover, the median level of serum HBV cccDNA was significantly higher in HBeAg positive patients in contrast to HBeAg negative subjects.

Secondary jaw aneurysmal bone cyst (JABC)--a possible misnomer? A review of literature on secondary JABCs, their pathogenesis and oncogenesis.

CONTEXT: Aneurysmal bone cysts are rare pseudocysts, commonly seen in long bones and vertebral column. Although a well described and reported lesion, many misconceptions still prevail regarding their etiopathogenesis. Many of the reported cases of jaw aneurysmal bone cysts (JABC) present with another bone pathology. AIMS: The purpose of this review was to evaluate the incidence of neoplastic lesions occurring simultaneously with a JABC (in contrast to primary JABCs). Any pathogenetic and oncogenetic association between primary and secondary jaw ABCs has been reviewed and discussed. SETTINGS AND DESIGN: A methodical narrative review of literature was performed, given the incidence of mostly case reports on this topic. METHODS AND MATERIAL: A methodical electronic search of Pubmed, Pubmed Central, Medline and Cochrane databases was performed for reported cases of JABC. These articles were analysed and segregated into primary and secondary ABC and, if secondary, the lesion it concurrently occurred with. Another search was conducted to yield articles discussing the cytopathogenetic and oncogenetic origins of ABCs. RESULTS AND CONCLUSIONS: About 15% of the ABCs reported were of secondary nature. Amongst the associated lesions, cement-ossifying fibroma and ossifying fibroma were the most common, followed by fibrous dysplasia and central giant cell granuloma. No ABCs were associated with metastatic changes. The search for histopathogenesis pointed to a specific cytogenetic abnormality as the origin of primary ABCs, with USP6 as its main oncogene and spindle cell as the neoplastic cell, unlike with secondary ABCs, suggesting that they are distinct pathological processes.

Intercellular adhesion molecule-1 as a drug target in asthma and rhinitis.

Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein receptor of the immunoglobulin superfamily. Endothelial cells, epithelial cells, leukocytes and neutrophils are the major cells expressing ICAM-1. Ligands of ICAM-1 are macrophage adhesion ligand-1, leukocyte function-associated antigen-1 and fibrinogen (extracellular matrix protein). In normal physiological conditions, engagement of ICAM-1 receptor with immunological cells surface ligands assists in homing and trafficking of inflammatory cells to distant tissues. ICAM-1 has also long been known to mediate cell-to-cell interaction during antigen presentation and outside-in cell signalling pathways. ICAM-1-mediated elevated inflammation is implicated in asthma. On respiratory epithelial cells surface, ICAM-1 acts as natural binding site for human rhinovirus (HRV), a common cold virus that ultimately causes exacerbation of asthma. This review presents the findings on the role of ICAM-1 in the complication of asthma and in particular asthma exacerbation by HRV.

Cerebrospinal Fluid Viral Escape on Highly Active Antiretroviral Therapy: Analysis from Single Tertiary Care Centre.

HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.

Hepatitis B virus reverse transcriptase mutations in treatment Naïve chronic hepatitis B patients.

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome lead to decreased susceptibility to nucleos(t)ide analogs approved for treatment of HBV infection. The aim of this study was to detect and analyze pre-existing HBV RT mutations in treatment naïve patients with chronic hepatitis B. Seventy one chronic HBV treatment naïve patients were enrolled from January 2009 to June 2011. HBV RT sequence analysis was done by using direct bidirectional sequencing of semi-nested PCR products. HBV genotypes were determined by multiplex PCR. Genotype D was found in 64 patients (90.1%) followed by genotype C and A which were present in 5 (7.0%) and 2 (2.8%) patients respectively. The results of the RT sequence analysis showed mutations in 34 (47.9%) patients. The rtH248N mutation was the most common mutation, accounting for 47.1% patients. Other common mutations included rtD263E/S, rtM129L, rtF122L/V/I, rtS135Y/H, rtQ149K, rtL91I, rtH126R, rtC256S/G, rtY257W, rtS259T and rtE271D, which were present in 26.5% (9/34), 29.4% (10/34), 20.6% (7/34), 20.6% (7/34), 20.6% (7/34), 17.6% (6/34), 14.7% (5/34), 14.7% (5/34), 11.8% (4/34), 11.8% (4/34) and 11.8% (4/34) patients respectively. The known primary drug resistance mutations were found in 3 (8.8%) patients. The present study shows the presence of RT amino acid substitutions in treatment-naïve patients with chronic hepatitis B, which may decrease susceptibility to available oral antiviral drugs. On the basis of the finding of this study, genotypic testing is recommended before the start of therapy in naïve patients, so that suitable antiviral drugs can be prescribed.

Success of antiviral therapy in chronic hepatitis C infection relates to functional status of myeloid dendritic cells.

Chronic hepatitis C infection poses a major global health predicament and appears to be potent threat to mankind. The treatment in wide use is interferon/ribavirin combination therapy which is generally effective in about 60-70 per cent of patients carrying genotype 3 and causes significant morbidity. The response to therapy is largely guided by limited number of factors such as genotype of virus, rapid virological response, ethnicity, pre-therapy viral load, etc. While involvement of host genetic factors has been a major focus of research in playing an important role in the outcome of disease, the role of immune system cannot be marginalized. Poor cellular trafficking and suboptimal T cell responses in liver, the hall marks of chronic hepatitis C virus infection, might be attributed to defective antigen presentation. Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease. Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy. In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

Nephrectomy in children: Comparison of stress response to laparoscopic and open methods.

AIM: To evaluate and compare the extent of surgical stress following laparoscopic nephrectomy (LN) and open nephrectomy (ON) in children. MATERIALS AND METHODS: Twenty consecutive children undergoing nephrectomy were randomized to LN or ON groups. Acid-base balance, blood glucose, acute phase proteins (C-reactive protein [CRP]) and inflammatory markers (interleukin-6 [IL-6]) were measured pre-operatively, as well as 4 and 24 h after surgery. The differences between the two groups were analyzed statistically (significance value for P < 0.05). RESULTS: The overall acid base status was more stable in LN. The fall in pH 4 h after surgery was more in ON (P = 0.440) and the difference in pH in ON 4 h and 24 h post-operatively was statistically significant (P = 0.002). In LN, significant difference was found in the base excess mean pre-surgery (mean -3.280 mEq/L) and 4 h post-surgery (mean -7.480 mEq/L) (P = <0.05), as well as between 4 h and 24 h after surgery (mean -2.660 mEq/L) (P = 0.011). The acute rise in CRP 24 h post-operatively in the ON (88.972 mg/L) was significantly higher when compared to both the pre-operative and 4 h post-operative values (P < 0.05). This rise was however, not statistically significant when compared to the 24 h post-operative value in LN (46.399 mg/L) (P = 0.062). The rise in IL-6, 24 h post-procedure in LN (mean 44.444 pg/ml) was statistically lower than that in the open group (mean 343.333 pg/ml) (P = 0.041). CONCLUSIONS: The stable acid-base status and lesser rise of CRP and IL-6 in LN lead to the conclusion that surgical stress caused by LN is less than ON.