Predictors of In-Hospital Mortality in Thrombotic Thrombocytopenic Purpura in Children in the United States: A Population Analysis.

BACKGROUND: Despite proven efficacy and increased availability of therapeutic plasma exchange, thrombotic thrombocytopenic purpura (TTP) is associated with significant morbidity and mortality. STUDY DESIGN AND METHODS: This study utilized the Kids' Inpatient Database and National Inpatient Sample (2003 to 2016) to study predictors of in-hospital mortality in hospitalized TTP patients. Adjusted odds ratios of death with various putative risk factors were calculated using multiple regression analysis. RESULTS: Among 1568 hospitalizations with TTP as primary admission diagnosis who underwent therapeutic plasma exchange, 69 deaths were identified (all-cause mortality, 0.04%; median time-to-death, 6 wk). Overall, hospitalizations rates were fairly similar across the study period. The overall incidence of TTP related hospitalizations is 1.51 per 100,000 hospitalizations. A total of 69 deaths were reported with an all-cause in-hospital mortality rate of 0.04% (69/1568). The median time-to-death was 6 weeks. The majority of deaths occurred in age 16 to 20 years (58%), females (56.5%), and African American (42.9%) as shown in Table 2. Mean age for nonsurvivors was 14 years and the mean age of 15 years for survivors (P=0.01). Younger age, male sex, African-American ethnicity, malignancy, sepsis, acute kidney injury, platelet transfusion was significantly associated with mortality in patients with TTP. CONCLUSIONS: Early and targeted therapy for high risk individuals should be used to guide management of TTP patients for improved survival outcomes.

Epidemiology, Comorbidities, and Outcomes of Posterior Reversible Encephalopathy Syndrome in Children in the United States.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized entity with certain identified predisposing factors in children. However, the actual incidence, comorbidities, outcomes, and hospitalization charges among children (aged less than 20 years) in the United States are largely unknown. METHODS: We analyzed the Kids' Inpatient Database for incidence of PRES-related hospitalizations, associated diagnoses, in-hospital outcomes, and charges for children in the United States in 2016. We report demographics, risk factors, discharge status, mortality, length of stay, and hospitalization charges. RESULTS: In 2016, 825 pediatric hospitalizations related to PRES were captured in the Kids' Inpatient Database. Hospital discharges including solid organ transplant, bone marrow transplant, hypertension, renal disorder, primary immunodeficiency, malignancy, sepsis, severe sepsis, systemic connective tissue disorder, blood transfusion, hypomagnesemia, and sickle cell anemia were queried for presence of PRES. The majority of patients were discharged home. We found that PRES-related hospitalizations were significantly associated with increased length of stay and hospitalization charges in 2016 (P < 0.001). A mortality rate of 3.2% was found in PRES-related hospitalizations when compared with 0.4% in non-PRES hospitalizations (P < 0.001). CONCLUSION: PRES accounted for 0.04% of the hospitalizations in this database. Hypertension and the presence of a renal disorder are the most significant risk factors found to be associated with PRES. The presence of PRES was associated with a significant increase in hospitalization charges and increased length of stay.

Multiple Pulmonary Nodules in an Immunocompetent Adolescent with Infectious Mononucleosis.

BACKGROUND: Infectious mononucleosis is usually a self-limiting illness, but can be rarely associated with complications. CASE CHARACTERISTICS: A 17-year-old boy with Epstein-Barr virus related infectious mononucleosis and cold antibody-mediated autoimmune hemolytic anemia with incidentally noted multiple pulmonary nodules. OBSERVATIONS: Nodules regressed over the next few weeks without specific therapy. MESSAGE: Pediatricians need to be aware of this rare clinical presentation of infectious mononucleosis so that further invasive testing can be avoided.

Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain.

The painful vaso-occlusive crises (VOC) that characterize sickle cell disease (SCD) progress over hours from the asymptomatic steady-state. SCD patients report that VOC can be triggered by stress, cold exposure, and, pain itself. We anticipated that pain could cause neural-mediated vasoconstriction, decreasing regional blood flow and promoting entrapment of sickle cells in the microvasculature. Therefore, we measured microvascular blood flow in the fingers of both hands using plethysmography and laser-Doppler flowmetry while applying a series of painful thermal stimuli on the right forearm in 23 SCD patients and 25 controls. Heat pain applied to one arm caused bilateral decrease in microvascular perfusion. The vasoconstriction response started before administration of the thermal pain stimulus in all subjects, suggesting that pain anticipation also causes significant vasoconstriction. The time delay between thermal pain application and global vasoconstriction ranged from 5 to 15.5 seconds and increased with age (P < .01). Although subjective measures, pain threshold and pain tolerance were not different between SCD subjects and controls, but the vaso-reactivity index characterizing the microvascular blood flow response to painful stimuli was significantly higher in SCD patients (P = .0028). This global vasoconstriction increases microvascular transit time, and may promote entrapment of sickle cells in the microvasculature, making vaso-occlusion more likely. The rapidity of the global vasoconstriction response indicates a neural origin that may play a part in the transition from steady-state to VOC, and may also contribute to the variability in VOC frequency observed in SCD patients.

Iron toxicity and its possible association with treatment of Cancer: lessons from hemoglobinopathies and rare, transfusion-dependent anemias.

Exposure to elevated levels of iron causes tissue damage and organ failure, and increases the risk of cancer. The toxicity of iron is mediated through generation of oxidants. There is also solid evidence indicating that oxidant stress plays a significant role in a variety of human disease states, including malignant transformation. Iron toxicity is the main focus when managing thalassemia. However, the short- and long-term toxicities of iron have not been extensively considered in children and adults treated for malignancy, and only recently have begun to draw oncologists' attention. The treatment of malignancy can markedly increase exposure of patients to elevated toxic iron species without the need for excess iron input from transfusion. This under-recognized exposure likely enhances organ toxicity and may contribute to long-term development of secondary malignancy and organ failure. This review discusses the current understanding of iron metabolism, the mechanisms of production of toxic free iron species in humans, and the relation of the clinical marker, transferrin saturation (TS), to the presence of toxic free iron. We will present epidemiological data showing that high TS is associated with poor outcomes and development of cancer, and that lowering free iron may improve outcomes. Finally, we will discuss the possible relation between some late complications seen in survivors of cancer and those due to iron toxicity.

Cardiac iron overload in sickle-cell disease.

Chronically transfused sickle cell disease (SCD) patients have lower risk of myocardial iron overload (MIO) than comparably transfused thalassemia major (TM) patients. However, cardioprotection is incomplete. We present the clinical characteristics of six patients who have prospectively developed MIO, to identify potential risk factors for cardiac iron accumulation. From 2002 to 2011, cardiac, hepatic, and pancreatic iron overload were assessed by R2 and R2 * magnetic resonance imaging techniques in 201 chronic transfused SCD patients as part of their clinical care. At the time, they developed MIO, five of six patients had been on chronic transfusion for more than 11 years; only one was on exchange transfusion. The time to MIO was correlated with reticulocyte and hemoglobin S percentages. All patients had qualitatively poor chelation compliance (<50%). All patients had serum ferritin levels >4600 ng/ml and liver iron concentration >22 mg/g. Pancreatic R2 * was >100 Hz in every patient studied (5/6). Cardiac iron rose proportionally to pancreas R2 *, with all patients having pancreas R2 *>100 Hz when cardiac iron was present. MIO had a threshold relationship with liver iron that was higher than observed in TM patients. In conclusion, MIO occurs in a small percentage of chronically transfused SCD patients and is only associated with exceptionally poor control of total body iron stores. Duration of chronic transfusion is clearly important but other factors, such as levels of effective erythropoiesis, appear to contribute to cardiac risk. Pancreas R2 * can serve as a valuable screening tool for cardiac iron in SCD patients.

Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload.

Ferritin levels and trends are widely used to manage iron overload and assess the efficacy of prescribed iron chelation in patients with transfusional iron loading. A retrospective cohort study was conducted in 134 patients with transfusion-dependent anemia, over a period of up to 9 years. To determine whether the trends in ferritin adequately reflect the changes in total body iron, changes in ferritin between consecutive liver iron measurements by magnetic resonance imaging (MRI) were compared to changes in liver iron concentrations (LIC), a measure of total body iron. The time period between two consecutive LIC measurements was defined as a segment. Trends in ferritin were considered to predict the change in LIC within a segment if the change in one parameter was less than twofold that of the other, and was in the same direction. Using the exclusion criteria detailed in methods, the trends in ferritin were compared to changes in LIC in 358 segments. An agreement between ferritin trends and LIC changes was found in only 38% of the 358 segments examined. Furthermore, the change in ferritin was in opposite direction to that of LIC in 26% of the segments. Trends in ferritin were a worse predictor of changes in LIC in sickle cell disease than in thalassemia (P < 0.01). While ferritin is a convenient measure of iron status; ferritin trends were unable to predict changes in LIC in individual patients. Ferritin trends need to be interpreted with caution and confirmed by direct measurement of LIC.

Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age.

Chronic blood transfusions start at a very young age in subjects with transfusion-dependent anemias, the majority of whom have hereditary anemias. To understand how rapidly iron overload develops, we retrospectively reviewed 308 MRIs for evaluation of liver, pancreatic, or cardiac iron in 125 subjects less than 10 years old. Median age at first MRI evaluation was 6.0 years. Median liver iron concentrations in patients less than 3.5 years old were 14 and 13 mg/g dry weight in thalassemia major (TM) and Diamond-Blackfan anemia (DBA) patients, respectively. At time of first MRI, pancreatic iron was markedly elevated (> 100 Hz) in DBA patients, and cardiac iron ( R2* >50 Hz) was present in 5/112 subjects (4.5%), including a 2.5 years old subject with DBA. Five of 14 patients (38%) with congenital dyserythropoietic anemia (CDA) developed excess cardiac iron before their 10th birthday. Thus, clinically significant hepatic and cardiac iron accumulation occurs at an early age in patients on chronic transfusions, particularly in those with ineffective or absent erythropoiesis, such as DBA, CDA, and TM, who are at higher risk for iron cardiomyopathy. Performing MRI for iron evaluation in the liver, heart, and pancreas as early as feasible, particularly in those conditions in which there is suppressed bone marrow activity is very important in the management of iron loaded children in order to prescribe appropriate chelation to prevent long-term sequelae. .

Novel STXBP2 mutation causing familial hemophagocytic lymphohistiocytosis.

Familial Hemophagocytic Lymphohistiocytosis (FHL) is a rare autosomal recessive disorder. Diagnosis is established in presence of genetic mutation or positive family history in one of the siblings. Common genetic mutations associated with FHL are mutations in gene PRF1 (also known as FHL 2), UNC13D (FHL 3) and STX11 (FHL 4). Recently mutation in STXBP2 encoding syntaxin binding protein 2 (Munc 18 -2) has been found to be associated with FHL type 5. Here we describe the first reported Indian patient with homozygous mutation in STX BP2 gene (c1697 G > A resulting in amino acid change p.G566D) causing FHL 5.

Costing of severe pneumonia in hospitalized infants and children aged 2-36 months, at a secondary and tertiary level hospital of a not-for-profit organization.

OBJECTIVES: To determine health care provider cost and household cost of the treatment of severe pneumonia in infants and young children admitted to secondary and tertiary level health care facilities. METHODS: The study was done in a private, not-for-profit medical college hospital, in Vellore, India, in mid-2008. Children aged 2-36 months admitted with severe pneumonia with no underlying chronic disease were included in the study. The relatives were interviewed daily on matters relating to patients' view point of the costs. These were direct medical costs, direct non-medical costs which comprised travel, accommodation and special food during the period of illness, and indirect costs of productivity loss for family members. Patient specific resource consumption and related charges were recorded from charts, nursing records, pharmacy lists and hospital bills, and the providers view point of the costs was estimated. Unit cost estimates for bed days, treatment and investigation inputs were calculated. RESULTS: Total cost to health care provider for one episode of hospitalized childhood pneumonia treated at secondary level was US$ 83.89 (INR 3524) and US$ 146.59 (INR 6158) at tertiary level. At both levels the greatest single cost was the hospital stay itself, comprising 74% and 56% of the total cost, respectively. Diagnostic investigations were a large expense and supportive treatment with nebulization and oxygen therapy added to the costs. Mean household expenditure on secondary level was US$ 41.35 (INR 1737) and at tertiary level was US$ 134.62 (INR 5655), the largest single expense being medicines in the former and the hospitalization in the latter. (one US$=INR 42.1 at time of study) CONCLUSIONS: A considerable cost difference exists between secondary and tertiary level treatment. Admission at lowest possible treatment level for appropriate patients could decrease the costs borne by the provider and the patient.

Prolonged neurologic course of familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis is a very unusual cause for demyelination and the clinician would do well to be aware of the condition, especially when children present with atypical findings on magnetic resonance imaging associated with fever, pancytopenia, and hepatosplenomegaly. This is a rare autosomal recessive, multisystem inflammatory disorder characterized by widespread organ infiltration by macrophages and activated lymphocytes. It is usually diagnosed in the first 2 years of life and is rapidly fatal if untreated. Reported here is the case of a 12-year-old boy, from a poor family, with a 6-year history of visual loss and fever for 5 months, and transient hemiparesis with hepatosplenomegaly and pancytopenia. Cranial magnetic resonance imaging showed multiple areas of hyperintense signal, predominantly involving white matter. The boy also had elevated triglycerides and ferritin, with low fibrinogen level. Bone marrow aspiration revealed hemophagocytosis. He was diagnosed as having familial hemophagocytic lymphohistiocytosis and treated with the HLH 2004 protocol. A sibling also had evidence of hemophagocytosis. Remission was achieved, but his parents could not afford the cost of hematopoietic stem cell transplantation. He relapsed after 8 months and later died.

Acute pancreatitis as the initial presentation in pediatric systemic lupus erythematosus.

It is exceptionally rare for acute pancreatitis to be the presenting manifestation of childhood systemic lupus erythematosus. We report a 14-year-old girl who presented with a history of fever, generalized rash, arthralgia and abdominal pain. Her serum amylase was 1472U/L and lipase 3316 U/L suggestive of acute pancreatitis. Other investigations revealed pancytopenia, low complement, high 24-hour urinary protein and elevated ANA and dsDNA. She was treated with IV methylprednisone, followed by oral steroids.

Intravenous magnesium sulphate infusion in the management of very severe tetanus in a child: a descriptive case report.

We report a 7-year-old boy with very severe tetanus treated with continuous infusion of magnesium sulphate for the control of spasms and severe autonomic dysfunction which was refractory to deep sedation and mechanical ventilation. The infusion was not associated with any adverse effects and he made an uneventful recovery. We recommend the use of intravenous magnesium sulphate infusion as an inexpensive and highly effective modality in severe tetanus.