Clinical Outcome and its Predictors in Children With Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVES: To determine the predictors for chronic and/or persistent ITP among children with newly diagnosed ITP. METHODS: Ours was a mixed-design study (prospective: January 2020 to March 2022 and retrospective: January 2014 to December 2019), wherein we enrolled children, aged 1 month to 18 years presenting with newly diagnosed ITP. RESULTS: Of the 64 enrolled participants, 58 were followed up for atleast 1-year duration and 6 children were followed up for 3 to 12 months' duration. The median (IQR) age of the cohort was 8 (5, 11) years with a female preponderance (62.5%). Wet bleeding was seen in 56%; 6.25% developed intracranial bleeding. 67.2% (43/64) and 41.2% (24/58) children developed persistent and chronic ITP, respectively. Of the 34 children who achieved complete response at 12-months follow up, 21 (62%) achieved complete response by 3 months and the rest achieved complete response over the next 9 months. Development of overall response (complete or partial) at 3 and 12 months, was associated with a higher absolute lymphocyte count (ALC) at admission. The median ALC (×103/µL) at admission was 3.77 and 2.87 in children who had overall response and no response at 3 months respectively (P = 0.03). The median ALC (×103/µL) at admission was 3.99 and 2.96 in children who had overall response and no response at 12 months respectively (P = 0.04). Response rate was lesser in the treated group by approximately 10% than the non-treated group, which could be an indicator of poor response probability in aggressive form of disease. CONCLUSION: The rate of chronicity and intracranial bleeding in our cohort is more than the reported rates in literature. Higher ALC was found to be associated with response.

Clinical Outcome and its Predictors in Children With Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVES: To determine the predictors for chronic and/or persistent ITP among children with newly diagnosed ITP. METHODS: Ours was a mixed-design study (prospective: January 2020 to March 2022 and retrospective: January 2014 to December 2019), wherein we enrolled children, aged 1 month to 18 years presenting with newly diagnosed ITP. RESULTS: Of the 64 enrolled participants, 58 were followed up for atleast 1-year duration and 6 children were followed up for 3 to 12 months' duration. The median (IQR) age of the cohort was 8 (5, 11) years with a female preponderance (62.5%). Wet bleeding was seen in 56%; 6.25% developed intracranial bleeding. 67.2% (43/64) and 41.4% (24/58) children developed persistent and chronic ITP, respectively. Of the 34 children who achieved complete response at 12-months follow up, 21 (62%) achieved complete response by 3 months and the rest achieved complete response over the next 9 months. Development of overall response (complete or partial) at 3 and 12 months, was associated with a higher absolute lymphocyte count (ALC) at admission. The median ALC (×103/µL) at admission was 3.77 and 2.87 in children who had overall response and no response at 3 months respectively (P = 0.03). The median ALC (×103/µL) at admission was 3.99 and 2.96 in children who had overall response and no response at 12 months respectively (P = 0.04). Response rate was lesser in the treated group by approximately 10% than the non-treated group, which could be an indicator of poor response probability in aggressive form of disease. CONCLUSION: The rate of chronicity and intracranial bleeding in our cohort is more than the reported rates in literature. Higher ALC was found to be associated with response.

Autoimmune Hemolytic Anemia in Children: Clinical Profile and Outcome.

OBJECTIVE: To discover the common triggers for AIHA in children, their clinical profile, treatment response, and outcome. METHODS: This was an ambispective descriptive study conducted between 2013 and 2020. Children aged 1 mo to 14 y with hemolytic anemia and a positive direct antiglobulin test (DAT) were included. Children with a positive DAT but without any clinicolaboratory evidence of hemolysis were excluded. Data were collected from a structured pro forma with particulars comprising clinicolaboratory profile, treatment administered, and disease outcome. RESULTS: A total of 46 children (aged between 1 mo and 14 y) were enrolled in the study. The mean age of onset was 8.7 (± 4.34) y, and 24 (52.8%) were males. Secondary causes were observed in 29 (63%) cases, while the primary cause was found in 17 (37%). Systemic lupus erythematosus (SLE) was the common trigger in 13 (45%) cases, followed by malignancy in 4 (14%) cases. Pallor (98%), hepatomegaly (72%), and splenomegaly (48%) were the most commonly observed clinical signs. The mixed immunophenotype was observed in 27 (59%) cases, followed by warm type in 12 (26%) and cold agglutinin type in 7 (15%) cases. All children received glucocorticoid therapy, and mycophenolate mofetil was commonly used as second-line therapy in 15 (33%) cases. 13 cases (71%) of primary AIHA and only 4 (14%) cases of secondary anemia achieved complete remission. Overall, 7 children (15%) died, all belonging to secondary AIHA. CONCLUSION: Secondary AIHA was more common than primary in the present study, and SLE was the standard trigger. Primary AIHA carries a better prognosis than secondary.

Evaluation of Bone Mineral Density in Children With Hemophilia: An Observational Case-Control Study.

OBJECTIVES: The objectives of this study were to study bone mineral content (BMC), bone mineral density (BMD), vitamin D level, and bone turnover markers in children with hemophilia and compare it with their normal counterparts. DESIGN: This was an observational case-control study. SETTING: This study was conducted in our tertiary care institute during the period spanning from September 2016 to June 2018. MATERIALS AND METHODS: A total of 38 children with hemophilia 2 to 18 years of age and 38 age-matched and sex-matched healthy controls were included. Children with symptomatic hypocalcemia and those receiving drugs affecting BMC and BMD were excluded. Dual-energy x-ray absorptiometry was performed to estimate BMC and BMD. 25-Hydroxyvitamin D [25(OH)D], intact parathormone, osteocalcin, calcium, phosphate and alkaline phosphatase, and spot urine pyrilinks-D/creatinine ratio were estimated in them. RESULTS: BMC and BMD in cases was lower than that in controls (P<0.05). Prevalence of low BMC was seen in 22 (58%) and low BMD in 8 (21%) of cases. All controls had normal BMC and BMD for age. The prevalence of low vitamin D level (<20 ng/mL) was seen in 36 (95%) among cases and in 25 (65%) among controls (P<0.001). Serum phosphorus was lower, and serum alkaline phosphatase was higher in cases than in controls (P<0.05). CONCLUSION: BMC, BMD, and vitamin D in hemophiliacs were lower than in the general population.

Effect of Vitamin D and Calcium Supplementation on Bone Mineral Content in Children with Thalassemia.

OBJECTIVE: To evaluate the effect of vitamin D and calcium supplementation for osteoprotection in thalassemia. METHODS: 29 children (age 2-12 y) were supplemented with oral vitamin D (1000 IU/d) and calcium (500 mg/d) for 1 year. The dual energy X-ray absorptiometry (DXA) was done to assess bone mineral content at baseline and 12 months. Serum 25-hydroxy vitamin D, intact parathyroid hormone, osteocalcin, calcium, phosphate, alkaline phosphatase, and spot urine deoxypyridinoline (DPD)/creatinine were done at baseline, 6 months and 12 months. RESULTS: The mean (SD) bone mineral content increased from baseline value of 8.4 (2.8) g to 10.8 (3.5) g (P<0.001). The mean (SD) vitamin D level increased from baseline value of 16.0 (5.8) ng/mL to 23.4 (6.6) ng/mL (P<0.001). The change in serum osteocalcin and spot urine DPD/creatinine ratio were not significant (P=0.062). CONCLUSION: Oral vitamin D and calcium supplementation increases bone mineral content in children with thalassemia.

Pediatric Thrombotic Events: Incidence, Clinical Risk Factors and Outcome.

OBJECTIVE: To study the incidence, clinical risk factors and outcome of thrombotic events in pediatric age group of 1 mo-12 y. METHODS: This prospective observational study was conducted in a tertiary care institute from September 2015 through October 2017. Forty nine children with thrombosis from 1 mo-12 y were enrolled. RESULTS: Out of 49 cases, 30 (61.2%) were due to venous thromboembolism (VTE) and 19 (38.8%) were of arterial thromboembolism (ATE). The cumulative average annual incidence for VTEs was found to be 38.2 (n = 30) and for ATEs it was found to be 24.2 (n = 19) per 10,000 hospital admissions over 2 y of study period. With total of 19 (38.7%), catheters were the leading cause of thrombosis followed by infection numbering to 10 cases (20.4%). Total 42.8% cases (n = 21) achieved complete resolution. Partial resolution was noted in 53.2% of cases (n = 26) and no resolution in 4% cases (n = 2). Total seven (14.3%) deaths were recorded during the study period. CONCLUSIONS: The present study showed that thrombosis is an emerging problem in tertiary care setting adding to both mortality and morbidity in children. Central venous catheters followed by infection were the leading cause of thrombosis in this study.

Antiphospholipid Syndrome Complicating Pneumococcal Meningitis.

BACKGROUND: Antiphospholipid syndrome is a multisystem auto-immune disorder characterized by arterial or venous thrombosis in children. CASE CHARACTERISTICS: 11-year-old child with pneumococcal meningitis also had cerebral sinus vein thrombosis and pulmonary artery segmental thrombosis. OBSERVATION: Pro-thrombotic evaluation showed positive lupus anticoagulant at baseline and after 12 weeks. Investigations for lupus were negative at admission and after one year of follow-up. MESSAGE: Antiphospholipid syndrome is a possibility even in thrombosis occurring in the setting of meningitis.

Kinetics and kinematics of diabetic foot in type 2 diabetes mellitus with and without peripheral neuropathy: a systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus patients are at increased risk of developing diabetic foot with peripheral neuropathy, vascular and musculoskeletal complications. Therefore they are prone to develop frequent and often foot problems with a relative high risk of infection, gangrene and amputation. In addition, altered plantar pressure distribution is an important etiopathogenic risk factor for the development of foot ulcers. Thus the review on study of foot kinematic and kinetic in type 2 diabetes mellitus to understand the biomechanical changes is important. METHODOLOGY: Scientific articles were obtained using electronic databases including Science Direct, CINAHL, Springer Link, Medline, Web of Science, and Pubmed. The selection was completed after reading the full texts. Studies using experimental design with focus on biomechanics of diabetic foot were selected. RESULTS: The meta-analysis report on gait velocity (neuropathy = 128 and non-diabetes = 131) showed that there was a significantly lower gait velocity in neuropathy participants compared to non-diabetes age matched participants at a high effect level (-0.09, 95 % CI -0.13 to 0.05; p < 0.0001). Regarding knee joint flexion range there was a significant difference between neuropathy and non-diabetes group (4.75, 95 % CI, -7.53 to 1.97, p = 0.0008). CONCLUSIONS: The systematic review with meta-analysis reported significant difference in kinematic and kinetic variables among diabetic with neuropathy, diabetic without neuropathy and non-diabetes individuals. The review also found that the sample size in some studies were not statistically significant to perform the meta-analysis and report a strong conclusion. Therefore a study with higher sample size should be done.

Atypical Presentation of Acute Lymphoblastic Leukemia in a 7 Year Old Child.

Seven year child, who had intussusception 4 month before, readmitted for fever and walking difficulty. On examination, child had mild pallor and kyphosis of the spine but no organomegaly, lymphadenopathy or bone pain . Further evaluation revealed hypercalcemia, diffuse osteoporosis with vertebral fracture. Peripheral smear showed no blasts or pancytopenia. Bone marrow aspiration turned out to be a pre B cell ALL. This child had many atypical presentations like intussusception, osteoporosis, vertebral collapse and hypercalcemia without any classical features of ALL.

Intrinsic foot muscle and plantar tissue changes in type 2 diabetes mellitus.

BACKGROUND: Diabetes mellitus is a metabolic disorder with involvement of the neurovascular and muscular system. Peripheral neuropathy (PN) is thought to be the principal cause of foot complications in type 2 diabetes mellitus (T2DM). However, foot evaluation using ultrasonography early in the course of diabetes has not gained due importance. The aim of the present study was to evaluate the thickness of intrinsic foot muscles, plantar skin, plantar fascia, and plantar fat pad in T2DM subjects with and without PN using musculoskeletal ultrasonography. METHODS: This study was conducted in 30 T2DM subjects with and without PN and 30 age-matched non-diabetes mellitus (NDM) subjects. After detailed clinical evaluation, high-frequency musculoskeletal ultrasonography was used to measure the thickness of the intrinsic foot muscles and plantar tissue thickness under the metatarsals. Data were analyzed using independent t-tests to compare T2DM groups with NDM subjects, and one-way ANOVA followed by Tukey's honestly significant difference test for between- and within-group analyses. RESULTS: There was a significant reduction in the thickness of the intrinsic foot muscles and plantar tissue in T2DM compared with NDM subjects (P < 0.05). However, there were differences in intrinsic foot muscle and plantar tissue thickness between T2DM subjects with and without PN. CONCLUSION: There was a substantial decrease in intrinsic foot muscle and plantar tissue thickness in T2DM compared with NDM subjects, indicating that structural changes appear in the foot before PN develops. The techniques used in this study cannot exclude the possibility that neuropathic changes that are clinically undetectable may develop in parallel with changes in plantar tissues.

Synthesis and biological evaluation of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents.

A series of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives 5, 6 and 7 were prepared starting from 6-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 3 via selective N-alkylation, followed by reaction with different primary aliphatic amines, cyclic secondary amines or l-amino acids under different set of conditions. All the synthesized compounds 5, 6 and 7 were screened for anticancer activity against four cancer cell lines such as A549-Lung cancer (CCL-185), MCF7-Breast cancer (HTB-22), DU145-Prostate cancer (HTB-81) and HeLa-Cervical cancer (CCL-2). The compounds 5i and 6e are found to have promising bioactivity at micro molar concentration.

Morbidity of ABO haemolytic disease in the newborn.

BACKGROUND: Better understanding of the clinical characteristics of ABO haemolytic disease in neonates helps optimise care. OBJECTIVE: To assess the morbidity associated with maternal-neonatal ABO incompatibility. METHODS: Neonates with blood groups A or B born to mothers with blood group O with simultaneous rhesus blood factor compatibility were studied prospectively. Maternal and neonatal details, direct Coomb's test (DCT) on the cord blood, onset and progression of jaundice, and requirement and duration of phototherapy were studied. Neonates requiring phototherapy were considered to have significant hyperbilirubinaemia, and peripheral smear, reticulocyte count and haematocrit values were obtained. ABO haemolytic disease of the newborn (ABO HDN) is defined as a newborn with a positive DCT and/or laboratory evidence of haemolysis such as reticulocytosis and spherocytes on blood smear. RESULTS: Of 878 deliveries, 151 (17.3%) neonates were ABO incompatible with their mothers. The proportions who were O-A and O-B incompatible were 50.4% and 49.6%, respectively. Forty-six (30.4%) had significant hyperbilirubinaemia (119.7-256.5 mmol/L) and required phototherapy, 26 (34.2%) of them in the O-A group and 20 (26.6%) in the O-B group. None required exchange transfusion. Jaundice was detected within the first 24 hours in 47.8%. Of 46 newborns who required phototherapy, 25 (54.3%) had laboratory evidence of haemolysis. DCT was positive in 1.9% of ABO-incompatible newborns. There was no significant difference in the incidence and severity of haemolysis between the O-A and O-B-incompatible neonates. Neonates with haemolysis required phototherapy significantly earlier and for longer than neonates without haemolysis (P<0.001). CONCLUSIONS: ABO incompatibility was observed in 17.3% of pregnancies with almost equal O-A and O-B frequency. About a third of infants had significant hyperbilirubinaemia. There was no difference in severity between those with O-A and O-B HDN.

Morphological study of lingula of the mandibles in South Indian population.

PURPOSE OF THE STUDY: The objectives were to study the morphology of the lingulae in adult human dried mandibles of South Indian population. MATERIALS AND METHODS: The study was carried out on 67 (37 males and 30 females) dry mandibles and the morphological variants of the shapes of the lingulae were macroscopically noted and classified. Totally, 134 lingula were studied from both sides of mandibles. RESULTS: From our observations, 29.9% (40) of the lingula had triangular shape, 27.6% (37) were truncated, 29.9% (40) were found nodular and 12.6% (17) were assimilated. In 61.2% (41) of the mandibles, the shape of the lingula was symmetrical on both the sides. The triangular lingulae were found bilaterally in 14, truncated in 11, nodular in 10 and assimilated in six mandibles. CONCLUSION: In our specimens, the majority of the mandibles were having triangular shaped lingula and the shape of the lingula was symmetrical on both sides. There was sexual dimorphism observed, as in males the triangular shape was more common and in females it was nodular. The incidence of different forms of lingulæ can be used as an anthropological marker to assess the different group of population and races, with other non-metric variants of the skull. The morphology of this subject is important to the maxillofacial and orodental surgeons as the inferior alveolar nerve is close to the lingula and may assist in the inferior alveolar block.

Morphometry of A1 segment of the anterior cerebral artery and its clinical importance.

BACKGROUND AND AIM: Anterior cerebral artery, one of the terminal branches of the internal carotid artery is an important vessel taking part in the formation of circle of Willis. It supplies a large part of the medial surface of the cerebral hemisphere containing the areas of motor and somatosensory cortices of the lower limb. Aim of this study was the morphometry of A1 segment of the anterior cerebral artery. MATERIALS AND METHODS: 93 formalin fixed brain specimen of either sex and of Indian origin were studied. The mean length, mean external diameter and the anomalies present in A1 segment of the vessel were studied in detail and photographed. RESULTS: The mean length of A1 segment of the vessel was 14.49+/-0.28 mm and 14.22+/-0.22 mm on right and left side respectively. The mean external diameter of the vessel on right and left side was 2.12+/-0.07 mm and 2.32+/-0.06 mm respectively. Narrowing, aneurysm formation, buttonhole formation and median anterior cerebral artery were the anomalies seen with an occurrence of 15.05%, 5.37%, 3.22% and 12.9%, respectively. The above anomalies did not have any sex or side predilection. CONCLUSION: Knowledge of morphometry of the vessel will be of use to neurosurgeons while performing the shunt operation, in assessing the feasibility of such operations and in the choice of patients. From this study we infer that the morphometry of anterior cerebral artery varies in different population and that the neurosurgeons operating should have a thorough knowledge of the possible variations.