Molecular epidemiology of HBV among HIV infected individuals in Chennai, south India.

Hepatitis B is a major co-infection among people with HIV (PWHIV) worldwide. There is a paucity of data on HBV genetic diversity in India, which would be useful for targeted preventive and management interventions. To characterize the distribution of HBV genotypes and sub-genotypes, samples of 180 HIV-HBV co-infected individuals from a study previously conducted to estimate the prevalence of HBV co-infection were analyzed. Nested PCR using type-specific primers was used to identify the various HBV genotypes. Partial HBV S sequences were generated for a subset of samples using Sanger sequencing. Mutation analysis was done using the online HBVseq program. PCR based genotyping documented D (69.4 %) and A (5.6 %) to be the major genotypes in the study population. Infection with multiple genotypes was observed in 25 % co-infected individuals. D2, D5, A2, and A1 were the sub-genotypes detected. Mutations 184K and 173L were identified. HBV genotypes/ sub-genotypes play a pivotal role in the clinical outcome of chronic hepatitis B (CHB). Therefore, monitoring of CHB cases is needed to track disease progression, including early detection of hepatocellular carcinoma.

Profile of patients with pulmonary non-tuberculous mycobacterial disease mimicking pulmonary tuberculosis.

INTRODUCTION: With the introduction of newer molecular diagnostic tools, an increasing number of Non-tuberculous Mycobacteria (NTM) affecting the respiratory system and mimicking symptoms of pulmonary tuberculosis (PTB) are being identified. They may be misdiagnosed and treated as PTB, often categorized as treatment failures if they do not respond to treatment. This manuscript aims to characterize patients with pulmonary NTM disease. METHODS: Patient characteristics of bacteriologically confirmed pulmonary NTM disease, attending the ICMR-National Institute for Research in Tuberculosis, Chennai were prospectively compiled over a two-year period (2017-2018). RESULTS: A total of 122 patients with recurrent chest symptoms and not responding to anti-tuberculosis treatment were screened for NTM. Thirty-nine cases (26 males and 13 females) of symptomatic pulmonary NTM were diagnosed. The mean (SD) patient age and body mass index were 48.6 ± 11 years and 16.3 ± 3. All male participants were smokers, had at least one episode of previous ATT. Mycobacterium kansasii (48.7%) was the most frequently isolated species followed by Mycobacterium intracellulare (20.5%), Mycobacterium abscessus (7.6%) followed by Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium kyorinense, and Mycobacterium simiae. Infection with multiple NTMs was seen in four patients. Isoniazid resistance was identified in 20 patients. Based on species identified, treatment was initiated as per American Thoracic Society guidelines and continued up to 12 months of culture negativity. CONCLUSIONS: M. kansasii is the commonest pulmonary NTM isolated in Tamilnadu with a higher prevalence in males and elderly. Sensitization of both patients and providers is essential to avoid misdiagnosis and delay in diagnosis of pulmonary NTM disease as pulmonary TB.

Impact of centralization of services on outcomes in a rare tumour: Retroperitoneal sarcomas.

BACKGROUND AND AIM: The retroperitoneal tumor (RPT) service in the North West costal region of England was centralized in May 2011 by the merger of the Merseyside, Cheshire and Lancashire, Cumbria sarcoma networks. Our aim was to analyze the impact of centralization of services on patient outcomes. METHODS: An analysis from 01/12/2004 to 30/11/2017 was undertaken from prospectively maintained database and electronic patient records; follow-up was until 30/04/2018. This time period encompassed 6.5 years before and after centralization of services took place. Survival analysis was done for Retroperitoneal Sarcomas (RPS) and also compared the impact of centralization. RESULTS: 72 patients (27 men), median age 69 (21-90) years) underwent 95 operations with an intention to excise RPS. Overall there were 52 (54.7%) multi-visceral resections (MVR). 91/95 (95.8%) patients with primary tumors had surgery with a curative (R0/1) intent. 30-day and 90-day operative mortality was 3.2% (n = 3) and 4.2% (n = 4) respectively. The 5-year survival for patients undergoing resection for RPTs was 51.3%. 79 (83.1%) of the resections in this series occurred in the 6.5-years post-centralization with an increase in MVR between the two time points (p < 0.0006). Despite the more radical nature of surgery post-centralization, there was no difference in 5-year survival for RPS patients when compared to pre-centralization, p = 0.575. However the 5-yr survival post-centralization compared favorability to national outcomes. CONCLUSION: Centralization in the management of RPS has resulted in an increase in resection rates and more complex MVRs, without compromising R0/1 resection rates; peri-operative mortality or overall survival.

Factors affecting high-density lipoprotein cholesterol in HIV-infected patients on nevirapine-based antiretroviral therapy.

BACKGROUND & OBJECTIVES: Cardiovascular disease (CVD) risk with low high-density lipoprotein cholesterol (HDL-C) and high triglycerides is common in the general population in India. As nevirapine (NVP)-based antiretroviral therapy (ART) tends to increase HDL-C, gene polymorphisms associated with HDL-C metabolism in HIV-infected adults on stable NVP-based ART were studied. METHODS: A cross-sectional study was conducted between January 2013 and July 2014 among adults receiving NVP-based ART for 12-15 months. Blood lipids were estimated and gene polymorphisms in apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genes were analyzed by real-time polymerase chain reaction. Framingham's 10-yr CVD risk score was estimated. Logistic regression was done to show factors related to low HDL-C levels. RESULTS: Of the 300 patients included (mean age: 38.6±8.7 yr; mean CD4 count 449±210 cell/µl), total cholesterol (TC) >200 mg/dl was observed in 116 (39%) patients. Thirty nine per cent males and 47 per cent females had HDL-C levels below normal while 32 per cent males and 37 per cent females had TC/HDL ratio of 4.5 and 4.0, respectively. Body mass index [adjusted odds ratio (aOR)=1.70, 95% confidence interval (CI) 1.01-2.84, P=0.04] and viral load (aOR=3.39, 95% CI: 1.52-7.52, P=0.003) were negatively associated with serum HDL-C levels. The 10-yr risk score of developing CVD was 11-20 per cent in 3 per cent patients. Allelic variants of APOC3 showed a trend towards low HDL-C. INTERPRETATION & CONCLUSIONS: High-risk lipid profiles for atherosclerosis and cardiovascular disease were common among HIV-infected individuals, even after 12 months of NVP-based ART. Targeted interventions to address these factors should be recommended in the national ART programmes.

Giant schwannoma of the medial plantar nerve.

In this article the authors present an exceptionally rare case of giant schwannoma of the foot in a 23 year old male. This article demonstrates the key principles of investigation and management of such cases as conducted by a regional sarcoma centre.

Profile and prevalence of HBV among HIV affected individuals attending the largest public HIV care center in India.

A large number of people living with HIV/AIDS residing in HBV endemic regions such as in India are highly susceptible to acquire co-infections like HBV but also transmit them to other due to their high risk behaviours. The present study aimed to estimate HBV prevalence and distribution of various HBV serological markers among HIV infected individuals. This cross sectional survey covered HIV infected individuals attending the largest HIV care center in India. Socio-demographic details and blood samples to screen for HBV seromarkers using commercial ELISA kits were collected. Among 1160 HIV infected patients, prevalence of HBcAb, HBsAb, HBsAg and HBeAg was 66, 29.4, 16.6 and 5.8 % respectively. Overall, 28.9 % individuals had no evidence of any of the four markers, indicating lack of previous exposure and future risk of acquiring HBV infection. Presence of anti-HBsAg in a mere 0.9 % of individuals reflected low levels HBV vaccine conferred immunity which could be due to poor HBV vaccine coverage in this high risk population. With high prevalence and evidence of exposure to HBV as well as considering the growing literature on increase in hepatic complications in HIV-HBV co-infected individuals, the need for mandatory HBV screening of all HIV infected individuals cannot be over-emphasised. The policy makers and HIV programme managers must consider HBV vaccination for newly detected HBV naive HIV infected individuals and also focus on creating public awareness on HBV and HIV prevention.

Stewart-Treves syndrome following idiopathic leg lymphoedema: remember sarcoma.

Patients with skin complaints secondary to oedema are commonly encountered and can be a diagnostic challenge. Here, we present the case of a 78-year-old lady with Stewart-Treves syndrome, a rare cutaneous angiosarcoma. The histology showed angiocutaneous sarcoma with poorly defined margins. The prognosis remains extremely poor. A successful transfemoral amputation reduced the massive tumour burden and cleared a source of sepsis from this fungating tumour. Our aim is to highlight this rare but high-grade sarcoma which results from chronic lymphoedema. The red flag signs of sarcoma are masses greater than 5 cm, tumours which are rapidly growing, deep to fascia or painful, and tumours that recur after previous surgery. Non-healing or progressive ulceration in the background of chronic lymphoedema should raise the possibility of underlying malignancy. We need a low threshold for biopsy and early referral to an appropriate multidisciplinary team for the optimum management of the patient.

Early changes in hepatic function among HIV-tuberculosis patients treated with nevirapine or efavirenz along with rifampin-based anti-tuberculosis therapy.

OBJECTIVES: To describe the longitudinal changes in hepatic function among HIV-infected tuberculosis (TB) patients receiving once-daily nevirapine (NVP)- or efavirenz (EFV)-based antiretroviral treatment (ART) along with rifampin-containing anti-TB treatment. METHODS: This was a nested study within a randomized clinical trial, taking place between May 2006 and June 2008 at the National Institute for Research in Tuberculosis, Chennai, India. Antiretroviral-naïve HIV-infected TB patients were initiated on an intermittent short-course regimen and randomized to receive didanosine and lamivudine with either NVP (400 mg) or EFV (600 mg) once-daily. Blood was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (SAP), and bilirubin at baseline, at ART initiation, fortnightly after ART initiation until 2 months, then monthly until 6 months and 6-monthly thereafter. RESULTS: Of the 168 patients included (79% men, median CD4 count 93 cells/mm3, median viral load 242,000 copies/ml), 104 were on EFV-based ART and 64 on NVP-based ART. There was a small but statistically significant elevation in ALT and SAP at 2 weeks and AST at 6 weeks after ART initiation. The proportion of patients with rate-limiting toxicity of liver enzymes was small. None had treatment terminated because of hepatotoxicity. CONCLUSION: Hepatotoxicity is not a major concern when HIV-infected TB patients, with normal baseline liver function initiate treatment for both infections simultaneously.

A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India.

BACKGROUND: The converging epidemics of HIV and tuberculosis (TB) pose one of the greatest public health challenges of our time. Rapid diagnosis of TB is essential in view of its infectious nature, high burden of cases, and emergence of drug resistance. OBJECTIVE: The purpose of this present study was to evaluate the feasibility of implementing the microscopic observation drug susceptibility (MODS) assay, a novel assay for the diagnosis of TB and multi-drug-resistant tuberculosis (MDR-TB) directly from sputum specimens, in the Indian setting. MATERIALS AND METHODS: This study involved a cross-sectional, blinded assessment of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV-negative patients against the radiometric method, BD-BACTEC TB 460 system. RESULTS: Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of the MODS assay in detecting MTB among TB suspected patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono-resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21 days (P<0.001). CONCLUSION: Costing 5 to 10 times lesser than the automated culture methods, the MODS assay has the potential clinical utility as a simple and rapid method. It could be effectively used as an alternative method for diagnosing TB and detection of MDR-TB in a timely and affordable way in resource-limited settings.

Zero CD4 count: a case of discordant CD4 response in a patient with well suppressed viral load.

Human immunodeficiency virus (HIV) positive patients continue to have raise in CD4 cell for several years after initiation of anti-retroviral therapy (ART). The discordant response of static or fall in CD4 cells in presence of well-suppressed viral load is an unusual finding. In this communication, we present a case report of an HIV patient in whom the repeated CD4 enumerations consistently showed zero/nil CD4 counts before and after the start of ART in spite of maximum viral suppression.

Giant osteochondroma of the talar neck.

Giant osteochondroma is an uncommon entity and it is rare in the foot and ankle region. It is extremely rare to originate from the talus. In this case report we present a case of giant osteochondroma arising from the talar neck measuring 100 mm × 90 mm × 30 mm. It is unique because of the size, site and the age at presentation.

Hindquarter amputation: is it still needed and what are the outcomes?

A total of 157 hindquarter amputations were carried out in our institution during the last 30 years. We have investigated the reasons why this procedure is still required and the outcome. This operation was used as treatment for 13% of all pelvic bone sarcomas. It was curative in 140 and palliative in 17, usually to relieve pain. There were 90 primary procedures (57%) with the remaining 67 following the failure of previous operations to control the disease locally. The indication for amputation in primary disease was for large tumours for which limb-salvage surgery was no longer feasible. The peri-operative mortality was 1.3% (n = 2) and major complications of wound healing or infection arose in 71 (45%) patients. The survival at five years after hindquarter amputation with the intent to cure was 45%, and at ten years 38%. Local recurrence occurred in 23 patients (15%). Phantom pain was a significant problem, and only 20% used their prosthesis regularly. Functional scores were a mean of 57%. With careful patient selection the oncological results and functional outcomes of hindquarter amputation justify its continued use.

Clinical implication of pretreatment neutrophil to lymphocyte ratio in soft tissue sarcoma.

INTRODUCTION: Elevated neutrophil to lymphocyte ratio has been identified as a prognostic indicator in malignancies whereas; its association with extremity and trunk soft tissue sarcoma remain unclear. The aim of this study is to determine the utility of full blood neutrophil lymphocyte ratio (NLR) in preoperative diagnosis and its predictive value for survival in patients managed for soft tissue sarcoma of the trunk and extremities. METHOD: 223 patients who presented with a soft tissue tumor were retrospectively reviewed. The study period was from January 2002-December 2009. Preoperative NLR as well as demographics, clinical and histopathological data were analysed. RESULTS: Full blood NLR was significantly higher in patient with a soft tissue sarcoma compared to benign soft tissue tumors (p < 0.001). Cox regression analysis demonstrated that elevated NLR >5 (p < 0.05) may be an adverse prognostic factor for Overall Survival. CONCLUSION: The preoperative NLR is a simple, investigation predicting the preoperative diagnosis of a soft tissue sarcoma and a predictor of worse overall survival for patient with a soft tissue sarcoma.

Initial virologic response and HIV drug resistance among HIV-infected individuals initiating first-line antiretroviral therapy at 2 clinics in Chennai and Mumbai, India.

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/µL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥ 70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART.

Pathological fracture of the proximal femur in osteosarcoma: need for early radical surgery?

Seventeen patients underwent treatment for a pathological fracture of the proximal femur due to osteosarcoma. Their age range was from 9 to 84 (mean age 42) with nine patients under the age of 40 and eight above the age of 40. Twelve patients had a fracture at diagnosis and five developed a fracture after the diagnosis. Seven patients had metastatic disease at diagnosis. Five patients were referred after internal fixation of the fracture prior to diagnosis. Chemotherapy was used when appropriate and eight patients then underwent limb salvage surgery, six had an amputation, and three had palliative treatment. The estimated five-year survival was 14%. These results are significantly worse than expected, and it proved impossible to identify any group who fared well. The high incidence of metastases both at diagnosis and subsequently suggests this group of patients are at very high risk. Review of multicentre data may suggest an optimum treatment for this patient group.

Outcome of pathologic fractures of the proximal femur in nonosteogenic primary bone sarcoma.

UNLABELLED: Pathologic fractures of the proximal femur resulting from primary bone sarcomas are often difficult to treat and some are often not recognized resulting in inappropriate interventions prior to the correct diagnosis being made. The aim of the study was to identify factors determining the survival after pathologic fractures of the proximal femur resulting from nonosteogenic primary bone sarcomas. PATIENTS AND METHODS: We retrospectively reviewed 72 patients with nonosteogenic primary bone sarcomas of the proximal femur (chondrosarcoma in 34 patients, spindle cell sarcoma in 25 and Ewing's sarcoma in 13). There were 40 male and 32 female patients. The mean age was 49 years. We analyzed patient, tumor, and treatment factors in relation to overall survival. The mean follow up was 55 months (range 0-302 months). RESULTS: The overall 5-year survival rate was 44% (Ewing's sarcoma 60%, chondrosarcoma 57%, spindle cell sarcoma 30%, and dedifferentiated chondrosarcoma 0%). The diagnosis of spindle cell sarcoma and dedifferentiated chondrosarcoma was the only significant factor adversely affecting survival. There was no difference in survival resulting from timing of the fracture, site of the fracture, age at diagnosis, surgical margin, limb salvage or amputation. CONCLUSIONS: The key-factor adversely affecting the survival after pathologic fractures of the proximal femur resulting from nonosteogenic primary bone sarcomas is the histological diagnosis of dedifferentiated chondrosarcoma and spindle cell sarcoma.

Management of radiation-induced sarcomas in a tertiary referral centre: a review of 25 cases.

INTRODUCTION: Radiation-induced sarcomas are a rare and late complication of radiotherapy for breast carcinoma which often have poor prognosis. METHODS: This study is a retrospective review of 25 patients referred to a regional sarcoma unit between 1978 and 2009. RESULTS: Radiation-induced sarcoma following the diagnosis and treatment of breast cancer occurred after a mean period of 156 months. Anatomical sites involved were the breast, chest wall, clavicle, scapula, humerus and axilla. Twenty one patients had wide local excision followed by chest wall reconstruction, latissimus dorsi flap cover or limb amputation. The estimated five years survival following the diagnosis of the radiation-induced sarcoma was 27% and the local recurrence rate 52%. CONCLUSION: Radiation-induced sarcoma following breast cancer has high local recurrence rate and poor prognosis. They should be managed in a multi-disciplinary setting. Long-term follow-up of patients treated with radiotherapy for breast cancer is therefore advisable.

Curettage of aneurysmal bone cysts of the feet.

BACKGROUND: Aneurysmal bone cysts (ABC) mainly occur in the long bones but only rarely in the bones of the feet. This study reviews the 25-year experience of a tertiary orthopaedic oncology referral center treating ABC's in the bones of the feet, using prospectively collected data to document their incidence, treatment and the outcome. MATERIALS AND METHODS: Information on the diagnosis, treatment, complications and outcomes were collected for all eligible patients from our prospectively collected database. Radiologic healing was used as our primary outcome measure. Cases were considered to have failed treatment if there was progression of the lesion that needed further treatment. RESULTS: Of 273 patients with ABC, 16 patients (5.9%) were found to have their lesions in the foot. There were ten female and six male patients, aged from 4 to 52 (mean, 18.2) years. The metatarsals were the most commonly affected site (44%). Curettage of the lesion without additional adjuvant measures (14 of 16 patients) was sufficient for the treatment in 11 of 14 patients (79%). This gave a recurrence rate of 21% (three of 14 patients) in those treated by curettage alone and 19% (three of 16 patients) if the whole cohort is considered. CONCLUSION: Although relatively rare, there is no reason to assume that ABCs of the feet will respond to treatment or recur any differently from ABCs that occur elsewhere in the body. Our experience has been that surgical curettage alone is sufficient to treat most ABCs of the feet.

HIV coinfection among multidrug resistant and extensively drug resistant tuberculosis patients--a trend.

Infection with human immunodeficiency virus (HIV) is found to increase the occurrence of drug resistant tuberculosis. The data for HIV and multidrug resistant tuberculosis (MDR-TB) coinfection is scarce in India. The study aims to find out the prevalence of MDR-TB and extensively drug resistant tuberculosis (XDR-TB) among chronic TB patients and to identify their trend with HIV coinfection over time. Non-responding chronic pulmonary tuberculosis patients were selected for the study from 2004 to 2007. They were all subjected to HIV screening and drug susceptibility testing (DST) for anti-TB drugs. In all 2927 chronic tuberculosis patients were assessed for DST and HIV coinfection; 2156 patients (73.7%) had culturable Mycobacterium tuberculosis in their sputum specimens; 1651 patients (56.4%) were found to have drug resistant mutants to one or more anti-TB drugs; 993 patients (33.9%) had MDR-TB and 48 (1.6%) had XDR-TB. Significantly, 17.9% of 1651 patients with drug resistance were found to have fluoroquinolone (ofloxacin) resistant strain. HIV was found to coexist with 141 (14.2%) of 993 MDR-TB patients. Three XDR-TB patients had HIV coinfection. The HIV coinfection was observed among MDR-TB patients to the tune of 12.3%, 14.7%, 17% and 12.6% during 2004, 2005, 2006 and 2007 respectively (p = 0.81). Prevalence of HIV coinfection with MDR-TB was found to be high among chronic TB patients. It would be appropriate to screen all the chronic TB patients for HIV coinfection apart from their sputa examined for drug resistant tuberculosis, especially in HIV high prevalent states. Indiscriminate use of fluoroquinolone should be stopped.