Profile of anemia in acute lymphoblastic leukemia patients on maintenance therapy and the effect of micronutrient supplementation.

BACKGROUND: Anemia is a common finding and important cause of morbidity in patients with acute lymphoblastic leukemia (ALL) at diagnosis or during the course of its protracted treatment. We studied profile of anemia in ALL patients on maintenance therapy and evaluated specific micronutrients as cause of this anemia. PATIENTS AND METHODS: ALL patients who were on maintenance therapy and had grade ≥ 2 anemia were recruited for the study. Serum iron studies, folate, and vitamin B12 were done to identify micronutrient deficiency and to initiate supplementation with specific components if found to be deficient. Toxicities, improvement of anemia, micronutrient levels, and disease outcome were studied after 3 months. RESULTS: From March 2015 to September 2016, 105 ALL patients were found to be on maintenance fulfilling the inclusion criteria. Overall, the proportion of anemia was 80%(N = 84). Majority had normocytic normochromic anemia (71%). Macrocytic anemia was seen in 18% and microcytic hypochromic in 9.5%. In patients with anemia of grade ≥ 2 (N = 84), 38 patients (45%) had biochemical deficiency of serum folate, and 7 (8%) had vitamin B12 deficiency. No biochemical evidence of iron deficiency was found. Supplementation of deficient micronutrients improved anemia: mean hemoglobin significantly increased from 8.06 ± 1.63 to 10.78 ± 1.53 (p < 0.001) at 3 months; and reduced treatment toxicities, mean number of febrile neutropenia episodes (p = 0.007), and treatment interruptions of > 2 weeks (p = 0.002) were lowered. Patients with anemia had significantly more relapses (N = 14,64%) compared to patients without anemia (N = 8,36%), (p = 0.040). CONCLUSION: Timely identification and correction of micronutrient deficiencies causing anemia in ALL patients on maintenance can enhance treatment outcomes.

Irisin and Visfatin Predicts Severity of Diabetic Nephropathy.

Although the roles of irisin and visfatin have been well established in diabetes mellitus, there are limited studies about their association in diabetic nephropathy. The present study was designed to assess the levels of irisin and visfatin and their association with the severity of diabetic nephropathy. 43 diabetic nephropathy cases and 43 diabetic subjects without nephropathy were enrolled in the study. Serum levels of irisin and visfatin were compared in both the groups. Irisin and visfatin were significantly increased in diabetic nephropathy cases when compared with diabetes subjects without nephropathy. eGFR was negatively correlated with visfatin (r = -0.323, p = 0.034), irisin (r = -0.324, p = 0.034), urine albumin (r = -0.443, p = 0.003) and albumin creatinine ratio (r = -0.419, p = 0.005) in patients with diabetic nephropathy. Visfatin was significantly elevated in stage IV nephropathy compared with stage III nephropathy. We conclude that irisin and visfatin are elevated in diabetic nephropathy and can be an index of its severity.

Clinical profile & complications of neurotoxic snake bite & comparison of two regimens of polyvalent anti-snake venom in its treatment.

BACKGROUND & OBJECTIVES: The optimal anti-snake venom (ASV) dose required to treat neurotoxic snake envenomation is not known. Low-dose ASV (national protocol: maximum dose 200 ml) may be as efficacious as the conventional regimen (100 ml six hourly till all symptoms disappear), but a direct comparison of the regimens is not available. The aim of this study was to test the efficacy of low-dose ASV regimen against the conventional high-dose regimen. METHODS: The clinical profile of 51 patients with neurotoxic snake envenomation was studied. Patients were treated with either the national protocol or the conventional protocol for ASV administration. The time to complete recovery of symptoms, duration of mechanical ventilation and total dose of ASV were compared. RESULTS: More patients were females (28 vs. 23) bitten in the early morning hours (2400-0600 h). Thirty nine of 51 (76.4%) patients required mechanical ventilation. In terms of progression of neuroparalysis, time to complete resolution of ptosis and occurrence of VAP and ASV reactions, there was no difference. Duration of mechanical ventilation was less with the national protocol (24 vs. 43.5 h). Significantly less amount of ASV was used with the national protocol (224 vs. 982 ml) per patient. There were no mortality or permanent neurological sequelae with either regimen. INTERPRETATION & CONCLUSIONS: In this preliminary study, it was found that the national ASV protocol was as effective as the conventional regimen for neurotoxic snake bites. However, the findings need to be tested in a larger randomized controlled trial for definitive conclusions.

A randomized study of very low-dose factor VIII prophylaxis in severe haemophilia - A success story from a resource limited country.

INTRODUCTION: Current factor prophylaxis strategy practised in developed countries is not feasible in resource constraint developing countries like India. AIM: The aim of this study was to investigate the efficacy and safety of very low-dose factor prophylaxis in India. METHODS: Children of 1-10 years of age with severe haemophilia were randomized to Prophylaxis group and Episodic (On demand) group. Children in prophylaxis group received very low-dose factor VIII (FVIII) concentrate, i.e. 10 units kg(-1) body weights on 2 days a week. Episodic group received factor concentrate in standard recommended doses. The study period was 11.5 months. RESULTS: In total 21 children were enrolled in this study, 11 assigned to prophylaxis and 10 to episodic group. Children on prophylaxis had 11 joint bleeds in comparison to 57 joint bleeds in episodic group. Mean number of haemarthrosis per patient per month were 0.08 (0.08 ± 0.13) in prophylaxis group compared to 0.48 (0.48 ± 0.34) in episodic group (P < 0.05). Total FVIII consumption was 87.51 and 56.32 units kg(-1) month(-1) in prophylaxis and episodic group respectively (P = ns). Overall median hospital emergency visits were 1 day in prophylaxis group and 9 days in episodic group (P ≤ 0.05). Median days of absenteeism from school were 25 days in episodic group and 3 days in prophylaxis group (P < 0.05). No significant complications were noted in prophylaxis group and compliance was 98%. CONCLUSION: To conclude, low-dose FVIII prophylaxis is cost effective, efficacious and a safe method of preventing joint bleeds and consequent joint damages.

Delayed Haemothorax Resulting from Indwelling Right Internal Jugular Central Venous Catheter: A Rare Complication.

Haemothorax is an uncommon and serious complication, occurring most often during or immediately after percutaneous internal jugular and subclavian vein catheterizations. Delayed haemothorax is a rare complication, especially following right-sided catheterization. We report a case of acute yellow phosphorus poisoning with acute liver failure (resulting from rat killer paste ingestion) in a 28-year-old male who developed right-sided haemothorax eight days after placement of right internal jugular central venous catheter. The proposed pathogenesis involves vascular wall erosion by the indwelling catheter tip. Awareness of this complication perhaps avoids unnecessary investigations for other causes of haemothorax such as pulmonary embolism.

Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier.

Congenital factor X (FX) deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

Inferior vena caval thrombosis: a rare complication of acute pancreatitis.

Inferior vena cava [IVC] thrombosis is a rare complication of acute pancreatitis. Here we report a case of IVC thrombosis with associated portal vein thrombosis complicating recurrent acute pancreatitis related to alcohol in a 31 year old male patient. We discuss the pathogenesis, clinical features and management of IVC thrombosis complicating acute and chronic pancreatitis in brief. The case is being reported for its rarity and early diagnosis as well as prompt treatment are essential for prevention of complications like pulmonary embolism.

Type 2 lepra reaction as a cause of pyrexia of unknown origin.

Leprosy, a commonly encountered disease, can rarely present as a reactional state de novo with fever as the main presenting feature. Here we describe an uncommon presentation of leprosy [with type 2 lepra reaction] as pyrexia of unknown origin with prominent rheumatologic manifestations [acute polyarthritis], renal involvement and generalized lymphadenopathy with rare presentation of type 2 lepra reaction without the classic skin lesions of erythema nodosum leprosum, occurring in a treatment naive patient without prior history of leprosy.

Association between serum netrin-1, netrin-4 and risk of the acute coronary syndrome in patients with type 2 diabetes mellitus-A pilot study.

The present study was done to assess the diagnostic utility of serum netrin-1 and netrin-4 for recognising the acute coronary syndrome (ACS) in type 2 diabetes mellitus (T2DM) patients. Forty-two T2DM patients with ACS (Cases) and forty-two T2DM patients without ACS (Controls) were compared. Cases had lower serum netrin-1 and netrin-4 levels than controls and were negatively associated with creatinine kinase-total, creatinine kinase-MB, troponin-T and H-FABP. ROC analysis showed that netrin-1 and netrin-4 had good sensitivity and specificity for ACS prediction in T2DM patients. Serum netrin-1 and netrin-4 levels might be considered complementary markers for ACS diagnosis in T2DM patients.

Defensive glands in the adult and larval stages of the darkling beetle, Luprops tristis.

Invasion by large populations of the litter-dwelling darkling beetle Luprops tristis Fabricius (Coleoptera: Tenebrionidae) following the short spell of summer rains during April, and their extended state of dormancy is a regular event in rubber plantation habitats in south-western India. Strong smelling secretions of the beetle cause blisters on skin of human beings. Such secretions appear defensive because they appear to facilitate their avoidance by other predatory organisms. Defensive glands in the larvae and adults of L. tristis are described, as well as the mode of eversion of the glands. The glands in larvae consist of two pairs of noneversible glands in a conical depression on the 2(nd) and 3(rd) sternites, whereas in adults only one pair occurs between 7(th) and 8(th) sternal segments. These glands may be a major reason for avoidance of larvae and adults by their natural enemies and their very high numbers in the litter of rubber plantations.

Population dynamics of the rubber plantation litter beetle Luprops tristis, in relation to annual cycle of foliage phenology of its host, the para rubber tree, Hevea brasiliensis.

The population dynamics of the rubber plantation litter beetle, Luprops tristis Fabricius 1801 (Coleoptera: Tenebrionidae) was assessed in relation to the phenology of leaf shedding and defoliation pattern of para rubber trees, Hevea brasiliensis Müll. Arg (Malpighiales: Euphorbiaceae), during a two year study period. The abundance of adults, larvae and pupae per 1m(2) of litter sample was recorded. Post dormancy beetles appeared in leaf litter following annual leaf shedding, whereas larvae, pupae and teneral adults were present after leaf flush. No stages were recorded from plantations following the summer rains until the annual litter fall in the next season. Parental adults peaked at the time of leaf sprouting and tender leaf fall. Larvae and teneral adults peaked at the time of premature fall of green leaves and flowers. Teneral adults of six age classes were recorded and all entered dormancy irrespective of the feeding time available to each age class. Females outnumbered males in the parent generation, while the sex ratio of new generation adults was not biased towards either sex. The phenological stages of rubber trees included leaf fall in late December and early January, leaf sprouting and new leaf production in January and flowering in February. All feeding stages of L. tristis peaked in abundance when premature leaves are most abundant in the leaf litter. Prediction of the timing of appearance of various developmental stages of L. tristis in plantations, invasion into buildings and intensity of population build up in rubber belts is possible by tracking the phenology of leaf fall in rubber plantations, time of return of post dormancy adults and the onset of summer rainfall. Perfect synchrony was recorded between the field return of parental adults with annual leaf shedding, the oviposition phase of parental adults with tender leaf fall at the time of leaf sprouting, and larval and teneral adult stages with premature fall of leaves. Premature leaf availability is suggested as contributing to the reproductive efficiency of parental adults, the survival of early developmental stages and of new generation adults during dormancy.

Food preferences of the rubber plantation litter beetle, Luprops tristis, a nuisance pest in rubber tree plantations.

Massive invasion of the litter dwelling beetle, Luprops tristis Fabricius (Coleoptera: Tenebrionidae), numbering about 0.5 to 4 million per residential building following summer showers, and their prolonged stay in a state of dormancy, make them an extreme nuisance in rubber tree plantation belts of the Western Ghats in south India. Food preference of post-dormancy adults, larvae and teneral adults stages towards tender, mature and senescent leaves were assessed in three choice and no choice leaf disc tests. All stages have strong preference towards fallen tender leaves and lowest preference towards senescent leaves indicating that leaf age is a major attribute determining food selection and food preference of L. tristis. Ready availability of the preferred, prematurely fallen, tender rubber tree leaves as a food resource is suggested as being responsible for the exceptionally high abundance of L. tristis in rubber tree plantation belts.

Sex determination of the live rubber plantation litter beetle, Luprops tristis: a novel method.

Absence of a discrete, externally visible gender-specific character makes sex determination of the rubber plantation litter beetle, Luprops tristis Fabricius (Coleoptera: Tenebrionidae: Lupropini), a difficult task. A new method based on a distinct notch on the 8(th) sternite of males that can be used to distinguish the sexes is described. This is the only method by which accurate sex determination of L. tristis could be done when culturing of live specimens is required. All alternative methods were found to be either inaccurate or led to higher mortality.

Life history, aggregation and dormancy of the rubber plantation litter beetle, Luprops tristis, from the rubber plantations of moist south Western Ghats.

Life history, aggregation and dormancy of rubber plantation litter beetle Luprops tristis Fabricius, (Tenebrionidae: Coleoptera) is described from rubber plantation belts in the western slopes of Western Ghats from the south Indian state of Kerala. The life cycle lasted 12 months, including the 5 larval instars lasting 1 month, the 3 day pupal stage, and the adult stage that can last 11 months. The adult stage includes an inactive dormancy phase of 9 months in shelters and 1 month each of active pre-dormancy (feeding) and post-dormancy (feeding and reproduction) phases that occur in rubber plantation litter. Reproductive activities are confined to the post-dormancy phase. With the onset of summer rains, huge aggregations of adults invade residential buildings and enter into a state of dormancy for 9 months. Beetle aggregations were in the range of 0.5 million to 4.5 million individuals per residential building. Dormancy in L. tristis is best classified as oligopause, which is intermediate between quiescence and diapause. Adults and larvae feed preferentially on wilted rubber tree leaves. Age-specific variation in mortality during dormancy is distinct with higher survivability for adults that have a longer pre-dormancy period. Generations are non-overlapping.

Ocular Manifestations in Leukemias and Their Correlation with Hematologic Parameters at a Tertiary Care Setting in South India.

PURPOSE: To determine the prevalence of ocular manifestations and the association of these manifestations with hematologic parameters among patients with leukemia attending a hemato-oncology unit at a tertiary care government hospital in South India. DESIGN: This was a cross-sectional observational study. PARTICIPANTS: All patients attending a hemato-oncology unit at a tertiary care government hospital in South India who were diagnosed with acute or chronic leukemia that was confirmed by a bone marrow biopsy. METHODS: Consecutive patients with leukemia presenting at the hematology clinic underwent standardized leukemia blood workup and comprehensive ophthalmic evaluation. Patient demographics, the type of leukemia, ophthalmic features, and hematological parameters such as hemoglobin level, white blood cell count, and platelet counts were recorded. The association between ophthalmic manifestations and blood counts was analyzed using multivariable regression analysis. MAIN OUTCOME MEASURES: The study measured the prevalence of various ocular manifestations in different types of leukemias and their association with hematologic parameters. RESULTS: In total, 133 eyes of 133 patients were examined during the study period. The prevalence of leukemic ophthalmopathy was found to be 68% in cases of acute myeloid leukemia, 42% in cases of acute lymphoid leukemia, 33% in cases of chronic lymphoid leukemia, and 13% in cases of chronic myeloid leukemia. Vision-threatening complications such as subhyaloid hemorrhage involving the posterior pole (20%) and vitreous hemorrhage (10%) were seen exclusively in patients with acute leukemias. Multivariable logistic regression after adjusting for the type of leukemia, patient age, and white blood cell and platelet counts showed that the hemoglobin level was the only factor predictive of developing subhyaloid hemorrhage (every 1-g/L increment increase in hemoglobin level led to a 30% reduction in the likelihood of developing subhyaloid hemorrhage; 95% confidence interval 0.5-0.9; P = 0.02). The probability of developing subhyaloid hemorrhage was reduced by >50% when hemoglobin level improved from 5 to 7 g/L and when platelet count improved from 10 000 to 50 000 cells/mm3 for both types of acute leukemia. There was no association between white blood cell counts and ophthalmic manifestations. CONCLUSION: Leukemic ophthalmopathy is more common in acute and myeloid cases and less common in chronic and lymphoid subtypes. It is predominantly due to secondary rheological changes. Blood transfusion should be considered when hemoglobin level and platelet count decrease below 7 g/L and 50 000 cells/mm3, respectively, to prevent vision-threatening complications. Patients with acute leukemias should undergo ophthalmic screening at baseline and then periodically to prevent visual morbidity.

Exploring circulatory shock and mortality in viper envenomation: a prospective observational study from India.

BACKGROUND: Viper envenomation contributes to nearly 50% of snake-bite deaths in India, chiefly due to circulatory shock. The mechanisms leading to circulatory shock include bleeding, capillary leak syndrome (CLS) and myocardial depression. Pituitary-adrenal axis involvement in circulatory shock, though described, has not been fully elucidated. AIM: To identify predictors of circulatory shock and mortality in viper envenomation and explore the role of pituitary-adrenal axis in circulatory shock. DESIGN: Prospective hospital-based observational study. METHODS: Once a syndromic diagnosis of viper envenomation was made, relevant clinical and laboratory data were collected. Serum cortisol was estimated in those with circulatory shock. Post-mortem examination of pituitary, kidneys and adrenals was performed. Adjusted odds-ratios were calculated for respective risk-factors for shock and mortality using multivariable logistic regression with backward elimination strategy. RESULTS: Of 248 patients of viper envenomation treated at our hospital, circulatory shock was present in 19% and in-hospital mortality was 23%. CLS, circulatory shock, bleeding and requirement of > 20 vials of antivenom predicted mortality. Ischaemic and haemorrhagic necrosis of pituitary or adrenals was present in 51% of post-mortem specimens. Disseminated intravascular coagulation (DIC) and CLS were strong predictors of pituitary haemorrhage. CONCLUSION: Predictors of mortality - bleeding, CLS and requirement of high antivenom doses are warning signs which can alert clinicians to patients who may have poor outcomes. Our study points to a definite role of pituitary-adrenal axis in circulatory shock supports the hypothesis that pituitary involvement in viper envenomation closely resembles Sheehan syndrome. The mechanism of pituitary involvement appears to be a result of increased susceptibility of the swollen gland secondary to CLS and micro thrombi deposition in DIC.