Velu Nair

Symptomatic portal system thrombosis in soldiers due to extended stay at extreme altitude

Background:  With induction of Indian Army to heights over 5000 m above mean sealevel (MSL), several new complications of long‐term stay at extreme altitude have come to light. The authors’ experience with soldiers who developed symptomatic portal system thrombosis (SPST) is described here.

The use of a fludarabine-based conditioning regimen in patients with severe aplastic anemia – a retrospective analysis from three Indian centers

Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA‐identical sibling or family donors. Seventy‐six patients were considered “high risk” as per criteria. The graft source included peripheral blood stem cells in 109 and G‐CSF‐stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini‐methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9–19) while platelet engraftment occurred at 12.4 d (range: 8–32). Grade II–IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five‐yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low‐risk group (n = 45) and 64.0 ± 5.6% in the high‐risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long‐term survival in patients undergoing HSCT for SAA.

Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report

IntroductionDiamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental.Case presentationWe report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin.ConclusionOur patients Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces.

BACKGROUND HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV - DNA by Real time - PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals. METHODS Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector. RESULTS Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy. CONCLUSION HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time - PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.

Effectiveness of homocysteine lowering vitamins in prevention of thrombotic tendency at high altitude area: A randomized field trial

INTRODUCTION A higher risk of thrombosis has been reported on prolonged stay at high altitude (HAA). Lowering of homocysteine (Hcy) has been found to reduce the risk of venous thrombosis. A randomized field trial was conducted with primary question whether Hcy lowering agents have any effect on the incidence of thrombosis at HAA amongst Indian soldiers as compared to existing interventions. METHODS All units freshly inducted to HAA were randomized into intervention (Vit B12 1000 microgram/day, B6 3mg/day & folic acid 5mg/day) and control arms, with a sample size of 12,000 person-years in each arm. RESULTS At the end of one year stay at HAA, Folate and B 12 levels decreased significantly in control arm. The levels of Hcy, fibrinogen and plasminogen activator inhibitor (PAI 1) were lower and nitric oxide higher in intervention arm as compared to control arm (p<0.05). At the end of 2years, 5 thrombotic episodes occurred in the intervention arm and 17 in control arm with RR of 0.29 (95% CI 0.11-0.80), attributable fraction % (AFe) 70.59%, Population attributable risk percent 54.55% and Protective Fraction 240%. CONCLUSION Intervention with B12 and folic acid is effective in reducing Hcy, PAI 1, fibrinogen levels and increasing NO levels at 1yr as compared to control arm and reducing the incidence of thrombosis at 2years of stay at HAA. Thus, vitamin B 12, B6 and folic acid intervention is safe and effective method of reducing morbidity and mortality caused by HAA induced coagulopathy.

Endocrine complications after busulphan and cyclophosphamide based hematopoietic stem cell transplant: A single tertiary care centre experience

Introduction: Endocrine complications are common after hematopoietic stem cell transplant (HSCT). Although HSCT is performed at various centers in India, no study is available for endocrine dysfunctions among them. This study was carried out with the objective to evaluate endocrine dysfunction among patients undergone HSCT in the past. Materials and Methods: We carried out a cross-sectional study in a 50 post-HSCT recipients (39 allogenic, 11 autologous). All relevant data were collected from patients records. Samples for hormonal estimation were collected and stimulation tests for cortisol and growth hormone were interpreted based on peak values achieved during insulin tolerance test. Results: The mean age of patients was 26.3 ± 16.9 years (range 4-74). Adrenal insufficiency (AI) was present in 60%, hypergonadotropic hypogonadism (HH) in 60%, growth hormone deficiency (GHD) in 54%, hypothyroidism in 4%, hyperprolactinemia in 4%, new onset diabetes after transplant in 4%, and impaired fasting glucose in 6%. Multiple endocrine complications were common. GHD was present in 77% of children (n = 22) although height standard deviation score was not statistically different compared to those who didn’t have GHD. HH was present in 36% of children. In adults (n = 28), 36% had GHD, all females had HH, and 89% of males had HH. Germ cell dysfunction with compensated Leydig cell dysfunction was the most common pattern of HH in males. Fifteen patients had graft versus host disease (GVHD). GVHD had no bearing on development of endocrine deficiencies. AI was related to duration after and type of transplant, but was unrelated to steroid intake. Conclusions: Endocrine manifestations are common after HSCT; they can occur as early or late complications. All HSCT recipients should have endocrine evaluation as per prevailing guidelines.

Immunosuppressive therapy in adults with aplastic anaemia: single-institution experience from India

Objective To determine overall survival and factors predicting survival after immunosuppressive therapy in patients with acquired aplastic anaemia. Design Retrospective. Setting Tertiary care hospital. Patients 120 adults diagnosed as having acquired aplastic anaemia between 1 January 1996 and 31 December 2009. Interventions Anti-thymocyte globulin (ATG) followed by ciclosporin was administered to all patients for 15–18 months as the initial treatment. Haematological response was assessed 6 months after ATG administration and 6-monthly thereafter. Platelets were transfused if levels were <10 × 103/l and for symptomatic bleeding. Transfusions of red blood cells were given for haemoglobin levels <70 g/l or symptomatic anaemia. Febrile neutropenia was managed with antibiotics, with the addition of antifungal agents after 3–4 days of unresponsive fever. Granulocyte colony-stimulating factor was administered at a dose of 5 µg/kg/day (maximum 300 µg/day) subcutaneously for infective episodes. Main outcome measures Primary outcome: overall survival. Secondary outcome: response to immunosuppressive therapy, failure-free survival, relapse and clonal evolutions. The response and relapse criteria were defined in accordance with the British Council for Standards in Haematology guidelines. Results Overall response at 6 months after initiation of treatment was 85.8% (103/120). Overall survival at 76 months was 83.4%. Overall survival correlated with presence of response (complete response or partial response) at 6 months after ATG administration (HR=0.021, 95% CI 0.006 to 0.079, p<0.001). The occurrence of infectious complications adversely affected the overall survival (HR=5.71, 95% CI 1.22 to 26.77, p=0.027). Six patients relapsed. There were no deaths or adverse events 12 months after treatment among responders. Conclusions In our study, overall survival was 83.4% at a median follow-up of 76 months. The two variables that significantly affected overall survival were response to therapy at 6 months and occurrence of infectious complications.

Profile of HIV patients on second line antiretroviral therapy: the Indian experience.

Background: The proportion of patients on second line in resource limited settings are estimated between 1-5%. The present study describes the profile and outcomes of Indian patients receiving second line ART. Methods: Information on HIV patients on second line ART was gathered. Socio demographic data, probable transmission route, baseline clinical parameters and comorbidities during therapy are studied along with first-line ART regimen initially introduced, its adherence and the reason for switch and components of the second-line ART regimen. Results: Out of the total 2174 HIV patients 53% were on first line ART and of these 51 patients on second line ART were studied. The average time of initiation of first line ART was 17.67 months with median of 2 months whereas switch to second line ART was in 53.75 months with median of 60 months. Almost 71% of the patients on second line ART had been diagnosed with HIV infection with low CD4 count of <200. However 54%, 67% and 58% patients show more than 50% rise in their CD4 count post switch to second line after 3, 6 and 12 months of treatment which is a substantial improvement. Twenty-five per cent of patients showed non adherence. Tenofovir based regimens had a slight advantage with lesser number of side effects being reported. Conclusion: Early diagnoses of infection, early initiation of ART and drug adherence are the cornerstones for success in managing HIV patients. Understanding the profile and drug resistance pattern is necessary for ensuring effective and long term survival.

Bedside ultrasonography as an alternative to computed tomography scan for the measurement of optic nerve sheath diameter

Background: Optic nerve sheath diameter (ONSD) as measured by optic nerve sheath ultrasonography (ONSU) is used as a surrogate marker of intracranial pressure (ICP), especially in resource-limited settings. There is a growing interest in the use of ONSU in emergency and high-altitude setups. Notwithstanding multiple studies done on this subject, there is a paucity of data regarding standardization of techniques and comparison of ONSU with computed tomography (CT). Materials and Methods: Thirty-five patients with a diagnosis of high-altitude cerebral edema were enrolled in the study. ONSD was measured in all patients using ONSU, along visual and coronal axis, and CT scan. We repeated ONSU in these patients on days 3, 7, 10, and 15 (day of discharge). Correlation between visual and coronal axis as well as CT scan was analyzed. Results: The correlation of visual to coronal and coronal to visual was equally significant (both correlation coefficients being R2 = 0.983). Correlation of ONSD by visual axis to CT scan was better than coronal axis (correlation coefficient R2 = 0.986 vs. 0.96, respectively). Conclusion: In our study, we found a strong correlation between the visual and coronal axes. Thus, either of the two axes can be used for monitoring ICP. However, it has been found that measurements along the coronal axis are challenging, especially in the emergency setup. ONSD measured along visual axis correlated better with CT scan as compared to the coronal axis.

Severe Symptomatic Diuretic Induced Hyponatremia

Dear Editor, A 66 year old man, a known case of primary hypertension and primary hypothyroidism was admitted with complaints of fatigue, weakness, lethargy and unsteadiness of gait of about 24 hours duration. He complained of dull headache for the last one week. There were no visual symptoms, loss of consciousness, seizures, sensory or motor symptoms, fever or vomiting. His comprehension was preserved. His treatment included Telmesartan 40 mg; Amlodepine 5 mg; Metoprolol XL 50 mg; Hydrochlorothiazide 25 mg and Thyroxine 50 mcg daily. Two days prior to admission his thiazide was increased from 12.5 mg to 25 mg and he had curtailed his salt intake. Clinical examination revealed a conscious but confused patient. He was disoriented to time, drowsy but easily arousable. His pulse was 72/min and had a blood pressure of 114/78 mmHg. He had no focal neurological deficits or any meningeal signs. His systemic examination was essentially normal. Investigations revealed haemoglobin12.9 gm/dl, total leucocyte count 7800 cells/cmm, blood urea 13.0 mg/dl and serum creatinine 0.8 mg/dl. The liver function tests showed serum bilirubin of 1.0 mg/dl, total proteins 7.0 g/dl, albumin 4.0 g/dl, SGOT 42 IU/L, SGPT 36 IU/L, alkaline phosphatase 79 IU/L. The serum sodium was markedly low 98 mEq/L, serum potassium was 3.1 mEq/L. A urinary spot sodium revealed 148 mEq/L. TSH was 6.0 μIU/ml (normal 0.3-6.5) and basal cortisol was 19.6 μg/dl. His serial serum sodium values are depicted in the graph (Fig 1). Fig. 1 Serial serum sodium values during the hospital course He was diagnosed as a case of chronic severe hyponatremia possibly due to use of diuretic and restriction of dietary salt intake (high urinary spot sodium in presence of hyponatremia). He tolerated severe hyponatremia well without any severe neurological manifestation probably indicating underlying chronic hyponatremia. Hence a gradual correction of sodium with hypertonic saline was planned (10 mEq/day). He was started with 3% normal saline at the rate of 30 ml/min (0.5ml/kg) [1]. On second day at 1800 hours his infusion was stopped in view of overcorrection. His serum sodium level again fell to 105 mEq/L in the morning next day which prompted restarting the 3% normal saline infusion at the rate of 20 ml/min. His serum sodium was gradually corrected to 126 mEq/L within 48 hours and his clinical condition improved. However his urinary sodium loss also increased. He was shifted to oral sodium replacement, 300 mEq with oral fluid replacement (1 Litre). His sodium level gradually increased by 8 mEq/day and he was discharged. The principal mechanism of thiazide induced hyponatremia is thought to be through the blockage of sodium chloride co transporter in the proximal part of distal tubule leading to excess sodium excretion [2]. Thiazides also induce excessive anti diuretic hormone activity with renal resistance attributable to associated hypokalemia [3]. Excessive water drinking during summer months also contributes to thiazide induced hyponatremia. Another proposed mechanism is the upregulation of aquaporin – 2 receptors in collecting duct by thiazides resulting in increased water absorption [4]. Severe hyponatremia is associated with high mortality, when treated aggressively (>20mEq/day) or when treatment is delayed. Our patient had the right setting for thiazide induced hyponatremia – his thiazide dose was recently increased, he had curtailed his salt intake and drank free water in excess due to prevailing extreme hot and humid weather. He was successfully treated with hypertonic saline, fluid restriction followed by oral salt. Recovery occurred in eight days. It has been reported that it usually takes 2-12 days for recovery of diuretic induced hyponatremia [3]. It must be remembered that overzealous and rapid correction of chronic symptomatic hyponatremia can have disastrous consequences, with irreversible neurological sequale.