Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study

BackgroundSurvivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust.MethodsTo define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ≥5 Gy (V5), ≥10 Gy (V10), ≥15 Gy (V15), and ≥20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function.ResultsOf the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3–13.2), and mean age was 31.4 years (IQR, 25.8–37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6–29.7). Approximately 2.1% had stages 3–5 CKD. Older age at evaluation; grade ≥2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ≥5 or ≥10 Gy increased the odds for stages 3–5 CKD. Nephrectomy was significantly associated with stages 3–5 CKD in models for V15 or V20.ConclusionsWe found that 2.1% of our cohort of childhood cancer survivors had stages 3–5 CKD. These data may inform screening guidelines and new protocol development.     

A novel ITGB2 variant with long survival in patients with leukocyte adhesion defect type-I

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with ≥ 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17 years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

     

Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation

Tyrosinemia type II is a rare autosomal recessive disorder caused by deficiency of tyrosine aminotransferase (TAT). It may occur with ocular and cutaneous symptoms with or without mental retardation, but epileptic seizure is a rare presentation of this disease. Herein we report the clinical, biochemical and genetic features of a 4‐year‐old boy who presented with afebrile seizure and photophobia. Genomic DNA was obtained from peripheral blood leukocytes from the whole family. Sequencing analysis was performed using the MiSeq next‐generation sequencing platform. Sequencing of TAT indicated two new homozygous mutations p.L312P (c.935T>C) and p.T408M (c.1223C>T) for the proband and his asymptomatic sister. During a 2 year follow‐up period, the patient had overall poor compliance with protein‐restricted diet, but his asymptomatic sister had good compliance with the diet. Cognitive function of the patient worsened steadily, but his asymptomatic sister maintained normal mental status. Tyrosinemia type II should be considered in the differential diagnosis of children presenting with epileptic seizure and photophobia; furthermore, early diagnosis and protein‐restricted regimen are important to reduce the risk of long‐term complications of tyrosinemia type II such as mental disability.     

The effect of glutamine supplementation on hematopoietic stem cell transplant outcome in children: A case–control study

Abstract:  HSCT associated morbidity and mortality is usually attributed to high-dose chemotherapy/radiotherapy regimens used for conditioning. Glutamine (Gln), a conditionally essential amino acid during severe catabolic states, has been shown to have favorable effects in patients with malignancies and in those undergoing HSCT. However, controversy exists regarding its routine use. Studies in children investigating gln supplementation are very limited. In the present study, including 21 gln-supplemented and 20 control pediatric patients, gln supplementation was shown to reduce the duration of fever and decrease the incidence of SOS during the HSCT course. In addition, a decrease in drug-related toxicity and a trend toward reduced incidence of severe mucositis were observed.     

Efficient and non-invasive method for investigating Helicobacter pylori in gravida with hyperemesis gravidarum: Helicobacter pylori stool antigen test

AIM: To investigate the relationship between Helicobacter pylori infection and severe hyperemesis gravidarum (H.Gravidarum) by using Helicobacter pylori Stool Antigen (HpSA) and other serologic test results. METHODS: Twenty-seven pregnant women with H.Gravidarum and 97 asymptomatic pregnant women of matching gestational age without gastric problems were enrolled in a prospective study. Serum samples collected from cases were investigated in terms of specific antibodies for H. pylori (immunoglobulin-IgG, IgA) and feces samples were investigated for HpSA. Statistical analysis of the data obtained from the groups was made by appropriate chi2 tests. RESULTS: Rate of HpSA positivity in patients with H.Gravidarum was 40.7%, while the same rate was 12.4% in the control group. The difference between the two groups was significant (P = 0.001). Rates of positivity for specific IgG formed against H. pylori in gravida with H.Gravidarum and in the asymptomatic gravida were 85.2% and 73.2%, respectively, and the rates for IgA were 48.1% and 41.2%, respectively. There was no difference between groups in terms of specific Igs formed against H. pylori (P > 0.05). CONCLUSION: The HpSA scan showed a statistically significant relation between H. pylori infection and H.Gravidarum. HpSA test gives more efficient, reliable and realistic results than specific Igs formed against H. pylori in the identification of H. pylori positivity in gravida with H.Gravidarum.     

Politics and health outcomes: A path analytic approach

Social and health policies and political participation are associated with each political tradition related to public health outcomes. However, there is a lack of evidence for the relationship between policy and outcomes. This study seeks to determine the relationship between politics, labour and welfare state indicators, economic inequality, and health outcome indicators. Data to test the model was obtained from the Turkish Statistical Institute (TurkStat) that belongs to the 81 provinces of Turkey. Path analysis was used to model the associations between policy, labour and welfare states, economic inequality, and health outcomes. To test the goodness of fit of the model, multiple criteria of model fit indices were utilised. The fit of the respecified path analytic model data is good (normed fit index [NFI] is 0.91, comparative fit index [CFI] is 0.92, goodness of fit index [GFI] is 0.91, and adjusted goodness of fit index [AGFI] is 0.93). Study results illustrate a strong relationship between voter partisanship, employment rate, satisfaction from both social security and health services, and life expectancy at birth and mortality. These results represent an important step towards understanding the elusive relationship between policy and health outcomes. Designing socially inclusive policies, considering labour market opportunities, and enhancing the population's well‐being are advisable strategies for policymakers who wish to optimise public health outcomes.     

The antihyperalgesic effect of cytidine-5'-diphosphate-choline in neuropathic and inflammatory pain models

This study was designed to test the effects of intracerebroventricularly (i.c.v.) administered CDP-choline (cytidine-5'-diphosphate-choline; citicoline) and its metabolites in rat models of inflammatory and neuropathic pain. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 μmol) produced a dose and time-dependent reversal of mechanical hyperalgesia in both carrageenan-induced inflammatory and chronic constriction injury-induced neuropathic pain models in rats. The antihyperalgesic effect of CDP-choline was similar to that observed with an equimolar dose of choline (1 μmol). The CDP-choline-induced antihyperalgesic effect was prevented by central administration of the neuronal high-affinity choline uptake inhibitor hemicholinium-3 (1 μg), the nonselective nicotinic receptor antagonist mecamylamine (50 μg), the α7-selective nicotinic ACh receptor antagonist, α-bungarotoxin (2 μg) and the γ-aminobutyric acid B receptor antagonist CGP-35348 (20 μg). In contrast, i.c.v. pretreatment with the nonselective opioid receptor antagonist naloxone (10 μg) only prevented the CDP-choline-induced antihyperalgesic effect in the neuropathic pain model while the nonselective muscarinic receptor antagonist atropine (10 μg) did not alter the antihyperalgesic effect in the two models. These results indicate that CDP-choline-elicited antihyperalgesic effect in different models of pain occurs through mechanisms that seem to involve an interaction with supraspinal α7-selective nicotinic ACh receptors, and γ-aminobutyric acid B receptors, whereas central opioid receptors have a role only in the neuropathic pain model.