DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.

Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized. Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants. Design, Setting, and Participants: In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research. Exposure: Centralized DNA sequencing of banked pretransplant remission blood samples. Main Outcomes and Measures: The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models. Results: Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P < .001) and decreased survival at 3 years (39% vs 63%; difference, -24% [2-sided 95% CI, -39% to -9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P < .001). Conclusions and Relevance: Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia.

Selective Self-Assembly of 5-Fluorouracil through Nonlinear Solvent Response Modulates Membrane Dynamics.

Controllable self-assembly and understanding of the interaction between single metabolite fibrils and live-cell membranes have paramount importance in providing minimal treatment in several neurodegenerative disorders. Here, utilizing the nonlinear nature and peculiar hydrogen bonding behavior of the dimethyl sulfoxide (DMSO)-water mixture, the selective self-assembly of a single metabolite 5-fluorouracil (5-FU) is achieved. A direct correlation between water availability and selective self-assembly of 5-FU is ratified from the excited-state dynamics. The specific fibrillar structures of 5-FU exhibit a great potential to modulate live cell membrane fluidity and model membrane lipid distribution. After 5-FU fibril addition, a disorder of H-bonded water molecules arises several layers beyond the first hydration shell of the polar headgroups, which essentially modifies interfacial water structure and dynamics. Overall, our results shed light on the role of solvent to govern specific self-assembly and also lay the foundation accounting for the earlier stage of several diseases and multidrug resistance.

Modulation of Membrane Fluidity Performed on Model Phospholipid Membrane and Live Cell Membrane: Revealing through Spatiotemporal Approaches of FLIM, FAIM, and TRFS.

We have elucidated the role of unsaturated fatty acid in the in vitro model phospholipid membrane and in vivo live cell membrane. Fluorescence microscopy and time-resolved fluorescence spectroscopy have been employed to uncover how modulation of vesicle bilayer fluidity persuades structural transformation. This unsaturation induced structural transformation due to packing disorder in bilayer has been delineated through spatially resolved fluorescence lifetime imaging microscopy (FLIM) and fluorescence polarization or anisotropy imaging microscopy (FPIM/FAIM). Structure-function relationship of phospholipid vesicle is also investigated by monitoring intervesicular water dynamics behavior, which has been demonstrated by temporally resolved fluorescence spectroscopy (TRFS) techniques. Nevertheless, it has also been manifested from this study that loss of rigidity in bilayer breaks down the strong hydrogen bond (H-bond) network around the charged lipid head groups. The disruption of this H-bond network increases the bilayer elasticity, which helps to evolve various kinds of vesicular structure. Furthermore, the significant influence of unsaturated fatty acid on membrane bilayer has been ratified through in vivo live cell imaging.

Membrane perturbation through novel cell-penetrating peptides influences intracellular accumulation of imatinib mesylate in CML cells.

Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. The use of first- and second-generation tyrosine kinase inhibitors has been successful to an extent. However, resistance against such drugs is an emerging problem. Apart from several drug-resistant mechanisms, drug influx/efflux ratio appears to be one of the key determinants of therapeutic outcomes. In addition, intracellular accumulation of drug critically depends on cell membrane fluidity and lipid raft dynamics. Previously, we reported two novel cell-penetrating peptides (CPPs), namely, cationic IR15 and anionic SR11 present in tryptic digest of Abrus agglutinin. Here, the potential of IR15 and SR11 to influence intracellular concentration of imatinib has been evaluated. Fluorescent correlation spectroscopy and lifetime imaging were employed to map membrane fluidity and lipid raft distribution following peptide-drug co-administration. Results show that IR15 and SR11 are the two CPPs which can modulate membrane fluidity and lipid raft distribution in K562 cells. Both IR15 and SR11 significantly reduce the viability of CML cells in the presence of imatinib by increasing the intracellular accumulation of the drug.

Unveiling the Self-Assembling Behavior of 5-Fluorouracil and its N,N'-Dimethyl Derivative: A Spectroscopic and Microscopic Approach.

Under physiological conditions, 5-fluorouracil (5-FU), an anticancer drug, self-assembles into fibrils by strong hydrogen-bonding network, whereas its N,N'-dimethyl derivative, 5-fluoro-1,3-dimethyluracil (5-FDMU), does not make fibrils due to lack of strong hydrogen-bonding motif. In vitro, 5-FU self-assembly is sensitive to physicochemical conditions like the pH and ionic strength of the solution, which tune the strength of the noncovalent driving forces. Here we report a surprising finding that the buffer, which is necessary to control the pH and is typically considered to be inert, also significantly influences 5-FU self-assembly, which indicates an important role of counterions in the fibril formation. We have also monitored concentration- and time-dependent fibrillar growth of 5-FU. Again, fibril growth process is probed under dynamic conditions using microfluidic platform. The self-assembly of 5-FU compared with its N,N'-dimethyl derivative shows lower cytotoxicity to the cultured human erythroleukemic cells (K562 cells), which plausibly states the reason behind the greater effectiveness of 5-FU derivative drugs than 5-FU itself.

Dravet syndrome with SCN1B gene mutation: A rare entity.

Early infantile epileptic encephalopathy has a grave outcome. Dravet syndrome (DS), characterized by early onset, refractory seizures, and intellectual deficit is one of the variants of the condition. SCN1B gene mutation is one of the lesser known variants of DS. Increased awareness of genetic analysis has increased the early diagnosis of DS for an early prognostication as well as genetic counselling of parents. We present the case of a 7-month old male child who started having recurrent febrile, and thereafter, afebrile seizures, following administration of a vaccination at 3 months. He developed global developmental delay, and is presently on multiple anticonvulsants. Genetic analysis was suggestive of SCN1B gene mutation associated with DS.

TP53 mutation screening for patients at risk of myeloid malignancy.

There is increasing recognition of the risk of developing therapy-related myeloid malignancy, including after cellular therapy. While retrospective studies have implicated pre-existing TP53 mutated hematopoietic clones as a common causative mechanism, no prospective screening to identify those patients at greatest risk is currently possible. We demonstrate that ultradeep DNA-sequencing prior to therapy may be used for discovery of TP53 mutations that are subsequently associated with malignancy.

Transient Neonatal Hypocortisolism in Neonates with Hypoglycemia - Coexistence or Cause?

Introduction: Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia. Methods: A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing. Results: All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was <50 mg/dl), hyperinsulinism (Insulin >2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 - 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months. Conclusion: The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted.

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.

Single- versus Divided-Dose Prednisolone for the First Episode of Nephrotic Syndrome in Children: An Open-Label RCT.

BACKGROUND: Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis suppression, but lack of robust evidence has resulted in variation in practice, with divided-dose prednisolone still commonly used. We conducted this open-label randomized control trial to compare HPA axis suppression between single-dose or divided-dose prednisolone among children with first episode of nephrotic syndrome. METHODS: Sixty children with first episode of nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided doses for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. The Short Synacthen Test was conducted at 6 weeks, with HPA suppression defined as postadrenocorticotropic hormone cortisol <18 µ mg/dl. RESULTS: Four children (single=1 and divided dose=3) did not attend the Short Synacthen Test and were hence excluded from analysis. Remission was induced in all, and no relapse postremission was noted during the 6+6 weeks of steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) versus single dose (83%) ( P = 0.02). Time to remission and final relapse rates were similar, but for those children who relapsed within 6 months of follow-up period, time to first relapse was shorter for divided dose (median 28 versus 131 days) P = 0.002. CONCLUSIONS: Among children with first episode of nephrotic syndrome, single-dose and/or divided-dose prednisolone were equally effective in inducing remission with similar relapse rates, but single dose had less HPA suppression and longer time to first relapse. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CTRI/2021/11/037940. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000216.mp3.

Challenges to manage primary chylopericardium in children.

Primary chylopericardium (PC) is a rare entity in the pediatric population with very few reported cases. Most cases of chylopericardium manifest after trauma or following cardiac surgery. The other etiologies which may lead to chylopericardium are malignancy, tuberculosis, or congenital lymphangiomatosis. We report two cases of PC in the pediatric population with contrasting outcomes. Both failed conservative management with dietary modification and octreotide. Surgery with pleuropericardial and pleuroperitoneal windows was performed in both. The first case had a thoracic duct ligation. The first patient died, and the second survived.

Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study.

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study. METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with TP53 mutations were classified as TP53multihit if two alleles were altered (via point mutation, deletion, or copy-neutral loss of heterozygosity). RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with TP53 (28% v 29%; P = .89), ASXL1 (23% v 29%; P = .37), and SRSF2 (16% v 16%; P = .99) being most common. OS in patients with a TP53 mutation was worse compared with patients without TP53 mutation (21% ± 5% [SE] v 52% ± 4% at 3 years; P < .001). Among those with a TP53 mutation, OS was similar between TP53single versus TP53multihit (22% ± 8% v 20% ± 6% at 3 years; P = .31). Considering HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% v 11% ± 7%; P = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; P < .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a TP53 mutation was significantly improved if they had a donor (68% ± 10% v 0% ± 12% at 3 years; P = .001). CONCLUSION: HCT improved OS compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high risk without a TP53 mutation had favorable outcomes when a donor was available.

Measurable Residual IDH1 before Allogeneic Transplant for Acute Myeloid Leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk.

Transfusion-associated necrotizing enterocolitis (NEC) in extremely preterm infants: experience of a tertiary neonatal center in UK.

OBJECTIVE: To compare the characteristics and short-term outcomes in extremely preterm infants, who developed necrotizing enterocolitis (NEC) following a packed red blood cell transfusion (pRBC) within 48 h (TANEC), with those who developed NEC beyond 48 h (non-TANEC). SETTING: A single-center retrospective cohort study in a Tertiary neonatal intensive care unit in the UK over a 5-year period. PATIENTS AND METHODS: Extremely premature infants (23-27 weeks gestation) were selected. TANEC and non-TANEC incidence were calculated from the confirmed NEC group (defined as modified Bell's stage II and beyond). The characteristics and short-term outcomes of infants with TANEC in the first 8 weeks of life were compared to infants with non-TANEC. RESULTS AND INTERPRETATION: Incidence of confirmed NEC was 14% (28/207). On further subgroup analysis of the confirmed NEC cases, 46% (13/28) of infants were identified with TANEC and 54% (15/28) with non-TANEC. The incidence of TANEC did not correlate with the number of antecedent pRBC transfusions or the pre-transfusion median hemoglobin (Hb) levels. There were no significant differences in characteristics between the TANEC and non-TANEC groups. Infants within the TANEC group required more intensive neonatal care support, greater surgical intervention (p-value 0.043) with loss of gut integrity and an increase in number of TPN dependency days (p-value 0.014). CONCLUSIONS: A significantly worse clinical course and short-term outcome was observed in the TANEC group when compared with the non-TANEC group.

Neonatal MIS-C: Managing the Cytokine Storm.

A term infant girl with uneventful antenatal history had an erythematous rash followed by fever from day 8. She was diagnosed with late-onset sepsis and was treated accordingly. She received immunoglobulin for persistent thrombocytopenia, after which there was transient improvement. The patient was transferred to our hospital on day 25 after recurrence of fever, watery diarrhea, and a generalized maculopapular rash. On admission, she had tachycardia, tachypnoea, anemia, thrombocytopenia, hypoalbuminemia, and generalized edema. Reverse transcriptase-polymerase chain reaction results for coronavirus disease 2019 (COVID-19) was positive. Within 12 hours of admission, she developed cardiogenic shock with pulmonary edema and needed invasive ventilation. Echocardiography revealed ejection fraction of 40% with mild pericardial effusion. N-terminal pro-brain natriuretic peptide was 33000 g/L, D-dimer 16500 µg/L, and ferritin 16000 ng/mL. Methylprednisolone, immunoglobulin, and enoxaparin was started, with a diagnosis of multisystem inflammatory syndrome in children, associated with COVID-19. She developed seizures, pulmonary hemorrhage, and cardiac arrest the following day, along with acute kidney injury. She was extubated after 5 days. Steroid was stopped after 5 days because she developed hypertension and echocardiography had normalized. Five days after extubation, she again developed respiratory distress and was ventilated again for 2 days. Echocardiography revealed moderate left ventricular dysfunction, along with secondary elevation of ferritin. Methylprednisolone was restarted and continued for 5 days followed by tapering dose of oral prednisolone, on which she was finally discharged. Although mild myocarditis with COVID-19 has been reported, multisystem inflammatory syndrome in children in a newborn with refractory myocarditis, along with gastrointestinal and renal manifestations, is a rare entity. Dermatologic manifestation of neonatal COVID-19 is also unique.

Clinico-Epidemiological Profile, Etiology, and Imaging in Neonatal Stroke: An Observational Study from Eastern India.

AIM: The aim of this study was to assess the clinico-epidemiological profile, etiology, and imaging findings in neonatal stroke (NS). MATERIALS AND METHODS: This was a retrospective, observational study on neonates presenting with stroke between August 2014 and July 2016 to a tertiary care hospital in eastern India. RESULTS: In all, 43 neonates were analyzed, with a male-to-female ratio of 2.3:1. About 88% babies were born at term and the rest were preterm. In 37%, the etiology of stroke was related to hypoxic injury, 21% had sepsis, and 35% had idiopathic causes. Seizures were the most common mode of presentation (62%) followed by poor feeding, abnormal tone, recurrent apnea, encephalopathy, and hemiparesis. There was an almost equal prevalence of ischemic stroke (53%) and hemorrhagic stroke (HS). Middle cerebral artery territory was the primary site of involvement in arterial ischemic stroke, and intra ventricular hemorrhage was the most common presentation of HS. CONCLUSION: NS is an acute emergency with high morbidity and mortality. Magnetic resonance imaging helps in diagnosis and prognostication in the absence or paucity of focal neurological signs in neonates.

X-Linked Myotubular Myopathy and Duchenne Muscular Dystrophy in a Preterm Infant: A Rare Combination.

Disorders of central and peripheral nervous system should be considered in floppy infants with ventilator dependence. Workup for neuromuscular disorders should be undertaken in infants with hypotonia, weakness, contractures, feeding difficulties, or failed attempts at extubation. We present the case of a preterm infant with hypotonia and ventilator dependence where despite a positive result, further investigations were undertaken because of lack of clinical correlation. The infant had a rare combination of 2 neuromuscular conditions: X-linked myotubular myopathy and Duchenne muscular dystrophy. One was the reason for immediate clinical manifestation and the other influenced the prognosis and decision-making in determining reorientation of care. This case demonstrates the value of interpretation of a positive result that did not explain the clinical picture and warranted consideration of further diagnosis. This case also emphasizes the importance of discussions with family about the prognosis of 2 conditions that influenced decision making.

Lipid Profile in Children With Thalassemia: A Prospective Observational Study From Eastern India.

This was a prospective observational study to evaluate abnormalities in lipid profile in 50 children with transfusion dependent thalassemia. Dyslipidemia characterized by high triglycerides, low high density lipoprotein (HDL), and high total cholesterol: HDL ratio was noted. These pro atherogenic risk factors may be lead to significant cardiovascular morbidity in these patients.