Jerusalem's CoVID-19 Experience-The Effect of Ethnicity on Disease Prevalence and Adherence to Testing.

BACKGROUND: The management of the SARS-CoV-2 pandemic depends amongst other factors on disease prevalence in the general population. The gap between the true rate of infection and the detected rate of infection may vary, especially between sub-groups of the population. Identifying subpopulations with high rates of undetected infection can guide authorities to direct resource distribution in order to improve health equity. METHODS: A cross-sectional epidemiological survey was conducted between April and July 2021 in the Pediatric Emergency Department of the Shaare Zedek Medical Center, Jerusalem, Israel. We compared three categories: unconfirmed disease (UD), positive serology test result with no history of positive PCR; confirmed disease (CD), history of a positive PCR test result, regardless of serology test result; and no disease (ND), negative serology and no history of PCR. These categories were applied to local prevailing subpopulations: ultra-orthodox Jews (UO), National Religious Jews (NRJ), secular Jews (SJ), and Muslim Arabs (MA). RESULTS: Comparing the different subpopulations groups, MAs and UOs had the greatest rate of confirmed or unconfirmed disease. MA had the highest rate of UD and UO had the highest rate of CD. UD significantly correlated with ethnicity, with a low prevalence in NRJ and SJ. UD was also associated with larger family size and housing density defined as family size per number of rooms. CONCLUSION: This study highlights the effect of ethnicity on disease burden. These findings should serve to heighten awareness to disease burden in weaker populations and direct a suitable prevention program to each subpopulation's needs. Early awareness and possible intervention may lower morbidity and mortality.

The use of a diversion tube to reduce blood culture contamination: A "real-life" quality improvement intervention study.

BACKGROUND: Blood culture contamination is associated with health care costs and potential patient harm. Diversion of the initial blood specimen reduces blood culture contamination. We report results of the "real-life" clinical implementation of this technique. METHODS: Following an educational campaign, use of a dedicated diversion tube was recommended prior to all blood cultures. Blood culture sets taken from adults using a diversion tube were defined as "diversion sets," those without, "non-diversion" sets. Blood culture contamination and true positive rates were compared for diversion and nondiversion sets and to nondiversion historical controls. A secondary analysis investigated efficacy of diversion by patient age. RESULTS: Out of 20,107 blood culture sets drawn, the diversion group included 12,774 (60.5%) and the nondiversion group 8,333 (39.5%) sets. The historical control group included 32,472 sets. Comparing nondiversion to diversion, contamination decreased by 31% (5.5% [461/8333] to 3.8% [489/12744], P < .0001]. Contamination was also 12% lower in diversion than historical controls [3.8% (489/12744) vs 4.3% (1,396/33,174) P = .02)]. The rate of true bacteremia was similar. In older patients, contamination rate was higher, and the relative reduction associated with diversion decreased (54.3% amongst 20-40-year-olds vs 14.5% amongst >80-year-olds). CONCLUSIONS: Use of a diversion tube in the ED reduced blood culture contamination in this large real life observational study. Efficacy decreased with increasing age, which requires further investigation.

A prospective study on myocardial injury after BNT162b2 mRNA COVID-19 fourth dose vaccination in healthy persons.

AIMS: To prospectively evaluate the incidence of myocardial injury after the administration of the fourth dose BNT162b2 mRNA vaccine (Pfizer-BioNTech) against COVID-19. METHODS AND RESULTS: Health care workers who received the BNT162b2 vaccine during the fourth dose campaign had blood samples collected for high-sensitivity cardiac troponin (hs-cTn) during vaccine administration and 2-4 days afterward. Vaccine-related myocardial injury was defined as hs-cTn elevation above the 99th percentile upper reference limit and >50% increase from baseline measurement. Participants with evidence of myocardial injury underwent assessment for possible myocarditis. Of 324 participants, 192 (59.2%) were female and the mean age was 51.8 ± 15.0 years. Twenty-one (6.5%) participants had prior COVID-19 infection, the mean number of prior vaccine doses was 2.9 ± 0.4, and the median time from the last dose was 147 (142-157) days. Reported vaccine-related adverse reactions included local pain at injection site in 57 (17.59%), fatigue in 39 (12.04%), myalgia in 32 (9.88%), sore throat in 21 (6.48%), headache in 18 (5.5%), fever ≥38°C in 16 (4.94%), chest pain in 12 (3.7%), palpitations in 7 (2.16%), and shortness of breath in one (0.3%) participant. Vaccine-related myocardial injury was demonstrated in two (0.62%) participants, one had mild symptoms and one was asymptomatic; both had a normal electrocardiogram and echocardiography. CONCLUSION: In a prospective investigation, an increase in serum troponin levels was documented among 0.62% of healthy health care workers receiving the fourth dose BNT162b2 vaccine. The two cases had mild or no symptoms and no clinical sequela. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05308680.

Hemoglobin A1C as a prognostic factor and the pre-diabetic paradox in patients admitted to a tertiary care medical center intensive cardiac care unit : The Jerusalem platelets thrombosis and intervention in cardiology (JUPITER-6) study group.

BACKGROUND: Hemoglobin A1C (HbA1c) is a form of glycated hemoglobin used to estimate glycemic control in diabetic patients. Data regarding the prognostic significance of HbA1c levels in contemporary intensive cardiac care unit (ICCU) patients is limited. METHODS: All patients admitted to the ICCU at a tertiary care medical center between January 1, 2020, and June 30, 2021, with documented admission HbA1c levels were included in the study. Patients were divided into 3 groups according to their HbA1c levels: < 5.7 g% [no diabetes mellitus (DM)], 5.7-6.4 g% (pre-DM), ≥ 6.5 g% (DM). RESULTS: A total of 1412 patients were included. Of them, 974 (69%) were male with a mean age of 67(± 15.7) years old. HbA1c level < 5.7 g% was found in 550 (39%) patients, 5.7-6.4 g% in 458 (32.4%) patients and ≥ 6.5 g% in 404 (28.6%) patients. Among patients who did not know they had DM, 81 (9.3%) patients had high HbA1c levels (≥ 6.5 g%) on admission. The crude mortality rate at follow-up (up to 1.5 years) was almost twice as high among patients with pre-DM and DM than in patients with no DM (10.6% vs. 5.4%, respectively, p = 0.01). Interestingly, although not statistically significant, the trend was that pre-DM patients had the strongest association with mortality rate [HR 1.83, (95% CI 0.936-3.588); p = 0.077]. CONCLUSIONS: Although an HbA1c level of ≥ 5.7 g% (pre-DM & DM) is associated with a worse prognosis in patients admitted to ICCU, pre-DM patients, paradoxically, have the highest risk for short and long-term mortality rates.

SARS-CoV-2 antibodies started to decline just four months after COVID-19 infection in a paediatric population.

AIM: We evaluated the prevalence of paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections using antibody testing and characterised antibody titres by time from exposure. METHODS: This was a single-centre, prospective, cross-sectional cohort study. Patients under 18 years old were eligible to participate if they attended the paediatric emergency department at the tertiary Shaare Zedek Medical Center, Jerusalem, Israel, from 18 October 2020 to 12 January 2021 and required blood tests or intravenous access. SARS-CoV-2 seropositivity and antibody levels were tested by a dual-assay model. RESULTS: The study comprised 1138 patients (56% male) with a mean age of 4.4 years (interquartile range 1.3-11.3). Anti-SARS-CoV-2 antibodies were found in 10% of the patients. Seropositivity increased with age and 41% of seropositive patients had no known exposure. Children under 6 years of age had higher initial antibody levels than older children, followed by a steeper decline. The seropositivity rate did not vary during the study, despite schools re-opening. The findings suggest that children's immunity may start falling 4 months after the initial infection. CONCLUSION: Immunity started falling after just 4 months, and re-opening schools did not affect infection rates. These findings could aid decisions about vaccinating paediatric populations and school closures.

[PROTEINURIA IN PATIENTS WITH ACUTE URINARY TRACT OBSTRUCTION].

AIMS: Urinary tract obstructions (UTO) induce tubular injury. The hypothesis explored in this study is that UTO can cause transient proteinuria. The aims of this study were to determine whether patients with UTO have a higher incidence/severity of proteinuria compared with catheterized patients without UTO and whether proteinuria resolves at short term follow-up. METHODS: This was a prospective, matched case control study that included 100 patients; 50 with acute UTO and 50 controls. Proteinuria was quantified using three consecutive 24-hour urinary collections during a week of hospitalization and its incidence, severity, and quantitative changes were compared between the study groups. RESULTS: Groups were similar by age (83.12±7.94 versus 84.48±9.39 (p=0.44)), major comorbidities, chronic medical treatment and causes of hospitalization. Abnormal proteinuria was observed in all patients with UTO and 94% of the control group. The degree of proteinuria was similar between the groups in the first, second and third 24-hour urine collections (638±419, 828±743, 728±944 vs. 620±639, 648±741, 732±841 mg/24 hours; p=0.88, 0.23 and 0.99, respectively). Proteinuria did not change significantly during a week of in-hospital follow-up in either study group (p=0.19 for trend). CONCLUSIONS: This study demonstrated a very high incidence of significant proteinuria in a cohort of hospitalized patients either with or without acute UTO. Proteinuria does not resolve in the early period after the relief of UTO. Future study with longer follow-up is needed to determine if this proteinuria resolves or persists following hospital discharge and if it has long-term prognostic significance.

Paracetamol Serum Concentrations in Neonates Treated Enterally for Ductal Closure: A Pilot Study.

We determined serum paracetamol concentrations 4 hours after the eighth dose in infants treated enterally for ductal closure. Serum paracetamol concentrations correlated (P = .0026) with ductal response. No patent ductus arteriosus in a baby with paracetamol levels <20 mg/L closed in response to treatment. Paracetamol levels also correlated (P = .046) with postnatal age.

Fetal Urine Production Rate in Preterm Premature Rupture of Membranes Is Associated with Adverse Neonatal Outcome: A Pilot Study.

AIM: In this study, we evaluate the associations between fetal urinary production rate (FUPR), measured by ultrasound, and adverse neonatal outcome in women with preterm premature rupture of membranes (PPROM). METHODS: We conducted a prospective pilot cohort of singleton pregnancies complicated by PPROM occurring at gestational week 24 or later managed until spontaneous labor (after 48 h of admission), chorioamnionitis, or induction by protocol at 35 + 0 weeks. FUPR was evaluated by 2D sonography at admission (corrected for gestational age). The main neonatal outcome measures were chorioamnionitis, placental inflammatory grading, first neonatal creatinine value, first neonatal dextrose value, length of neonatal intensive care unit (NICU) stay, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) (grades I-IV), blood transfusions, reduced neonatal urine production rate (<4 mL/kg/h), and early neonatal sepsis. Samples of maternal (at admission) and umbilical cord blood were analyzed for interleukin-6 (IL-6) level. RESULTS: The study included 38 women. Low FUPR was associated with clinical chorioamnionitis, longer NICU hospitalization (p = 0.01), higher rates of NEC or IVH (p = 0.008), and blood transfusion (p = 0.004). CONCLUSIONS: A finding of FUPR on in utero ultrasound examination in pregnancies complicated by PPROM may be indicative of adverse neonatal outcome.

Prediction value of anti-Mullerian hormone (AMH) serum levels and antral follicle count (AFC) in hormonal contraceptive (HC) users and non-HC users undergoing IVF-PGD treatment.

Use of hormone contraceptives (HC) is very popular in the reproductive age and, therefore, evaluation of ovarian reserve would be a useful tool to accurately evaluate the reproductive potential in HC users. We conducted a retrospective cohort study of 41 HC users compared to 57 non-HC users undergoing IVF-preimplantation genetic diagnosis (PGD) aiming to evaluate the effect of HC on the levels of anti-Mullerian hormone (AMH), small (2-5 mm), large (6-10 mm) and total antral follicle count (AFC) and the ability of these markers to predict IVF outcome. Significant differences in large AFC (p = 0.04) and ovarian volume (p < 0.0001) were seen, however, there were no significant differences in small and total AFC or in serum AMH and FSH levels. Oocyte number significantly correlated with AMH and total AFC in HC users (p < 0.001) while in non-HC users these correlations were weaker. In HC users, the significant predictors of achieving <6 and >18 oocytes were AFC (ROC-AUC; 0.958, p = 0.001 and 0.883, p = 0.001) and AMH (ROC-AUC-0.858, p = 0.01 and 0.878, p = 0.001), respectively. The predictive values were less significant in non-HC users. These findings are important in women treated for PGD, in ovum donors and for assessing the fertility prognosis in women using HC and wishing to postpone pregnancy.

Glucose-6-Phosphate Dehydrogenase Screening in Israel-Arab and Palestinian-Arab Neonates.

OBJECTIVE: To evaluate the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, the incidence of clinically significant jaundice (any serum total bilirubin value >75th percentile on the hour-specific bilirubin nomogram), and the need for phototherapy in the pooled male Israeli-Arab and Palestinian-Arab population born at the Shaare Zedek Medical Center in Jerusalem, Israel. STUDY DESIGN: Quantitative G-6-PD enzyme testing of umbilical cord blood was performed during birth hospitalization. G-6-PD deficiency was defined as any G-6-PD value <7.0 U/gHb. Transcutaneous bilirubin was performed daily during birth hospitalization, with serum total bilirubin testing in those with a transcutaneous bilirubin value >75th percentile. RESULTS: Ten of 286 (3.5%) consecutively delivered male Arab newborns had G-6-PD deficiency. Clinically significant jaundice was higher in the population with G-6-PD deficiency compared with normal controls (relative risk, 3.45; 95% CI, 1.24-9.58). Thirty percent of the newborns with G-6-PD deficiency met American Academy of Pediatrics indications for phototherapy according to the high-risk (middle) curve on the phototherapy graph. CONCLUSION: The frequency of G-6-PD deficiency in the Arab neonatal population delivering at this medical center meets World Health Organization criteria for neonatal G-6-PD screening (3%-5%). As in other ethnic groups, clinically significant jaundice is more frequent in newborns of this ethnic group with G-6-PD deficiency compared with G-6-PD-normal controls. Neonatal G-6-PD screening for both males and females of this population subgroup, in conjunction with parental education regarding the dangers of the condition and its prophylaxis, has now been incorporated into our institution's routine G-6-PD screening program.

Rapid fecal calprotectin (FC) analysis: point of care testing for diagnosing early necrotizing enterocolitis.

OBJECTIVE: The aim of this study is to compare fecal calprotectin (FC) levels as measured by a rapid FC assay with those measured by enzyme-linked immunosorbent assay (ELISA) from concurrent stool samples. We also attempted to demonstrate a correlation between elevated rapid assay FC levels and the presence of necrotizing enterocolitis (NEC) and to define a cutoff FC value which could serve as a basis for diagnosing NEC in the future. STUDY DESIGN: Stool samples were collected for FC analysis at 1 and 3 weeks postnatally and whenever there was clinical suspicion of NEC. RESULTS: Rapid assay FC levels were elevated with NEC (3,000 µg/g stool [2075,7875] vs. without (195 µg/g stool [110,440] p < 0.001); and were well correlated with ELISA FC levels (r(2) = 0.89). CONCLUSION: We present the first data showing that rapid assay FC levels are potentially useful in the bedside diagnosis of NEC.

Thiopurine S-methyltransferase (TPMT) activity is better determined by biochemical assay versus genotyping in the Jewish population.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is a key enzyme that deactivates thiopurines, into their inactive metabolite, 6-methylmercaptopurine. Intermediate and low TPMT activity may lead to leukopenia following thiopurine treatment. The aim of this study was to determine TPMT activity and TPMT alleles (genotype-phenotype correlation) in Jews, aiming to develop an evidence-based pharmacogenetic assay for this population. METHODS: TPMT activity was determined in 228 Jewish volunteers by high performance liquid chromatography. Common allelic variants in the Caucasian population [TPMT*2 (G238C), TPMT *3A (G460A and A719G), TPMT* 3B (G460A) and TPMT*3C (A719G)] were tested. Phenotype-genotype correlation was examined and discordant cases were fully sequenced to identify novel genetic variants. RESULTS: Mean TPMT activity was 15.4 ± 4 U/ml red blood cells (range 1-34). Intermediate activity was found in 33/228 (14%) subjects and absent activity was found in one sample (0.4%). Only eight individuals (3.5% of the entire cohort and 24% of those with intermediate/low activity) were identified as carriers of a TPMT genetic variant, all of whom had the TPMT*3A allele. Sequencing the entire TPMT coding region and splice junctions in the remainder of the discordant cases did not reveal any novel variants. CONCLUSION: Genotyping TPMT in Jews yields a much lower rate of variants than identified in the general Caucasian population. We conclude that a biochemical assay to determine TPMT enzymatic activity should be performed in Jews before starting thiopurine treatment in order to identify low activity subjects.

Urinary neutrophil gelatinase-associated lipocalin for early detection of acute kidney injury in geriatric patients with urinary tract infection treated by colistin.

INTRODUCTION: Colistin (polymyxin E) was developed ~ 60 years ago but was rarely used in clinical practice during the last 20 years because of concerns related to high rates of nephrotoxicity. However, it was recently reintroduced to clinical practice in many parts of the world for the treatment of multi-drug resistant gram-negative bacilli. In the current study, we evaluated the predictive capacity of urine neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of acute kidney injury (AKI) in geriatric patients with urinary tract infection (UTI) receiving colistin therapy. METHODS: We studied 116 patients aged 80.7 ± 12 treated with colistin who suffered from UTI. Urinary NGAL was measured at baseline and 1 - 2 hours after the second dose of colistin. The primary outcome was AKI. Secondary outcome was in-hospital morbidity and mortality. RESULTS: 52 patients (44.8%) developed acute tubular necrosis (ATN) (14% of these had underlying CKD), 8 (7%) had prerenal azotemia, 8 (7%) had stable CKD without changes in renal function during hospitalization and the remaining 48 patients (41%) had normal kidney function. The mean duration of colistin therapy was 9.1 ± 4.8 days. At baseline, urine NGAL was 405 ± 452 g/l in ATN, 285 ± 256 g/l in prerenal azotemia, 390 ± 468 g/l in CKD and 347 ± 877 g/l in normal kidney function patients (difference non-significant). We were unable to demonstrate statistically significant increments of urine NGAL following colistin administration in either ATN or non-ATN patient groups. Urine NGAL was not correlated with urinary leukocyte or erythrocyte counts or baseline comorbidities such as CKD, heart failure, or diabetes. For primary outcome (ATN), receiver operating characteristics curve revealed AUC 0.59 (95% CI 0.49 - 0.7) sensitivity 0.65, and specificity 0.62 for a cutoff value of urinary NGAL 140 g/l. Similar results were obtained for secondary outcomes. CONCLUSIONS: Our data suggest limited predictive capacity of urinary NGAL for early diagnosis of AKI in a large clinical setting of geriatric patients hospitalized for UTI and receiving the potentially nephrotoxic colistin. This finding is likely due to the powerful influence of UTI on NGAL levels in both patients with normal kidney function and those with a wide spectrum of acute or chronic kidney diseases.

Brain biomarkers and management of uncertainty in predicting outcome of cardiopulmonary resuscitation: a nomogram paints a thousand words.

AIM: Use of brain biomarkers for predicting death after cardiopulmonary resuscitation (CPR) is limited by a research focus on the discriminative ability of each biomarker and ethical/cultural controversy concerning the likelihood of misclassification of potential survivors. We illustrate an approach to address these limitations by creating a dynamic nomogram with four levels of sensitivity (0.8, 0.9, 0.95 and 1.0) selected to represent different degrees of certainty in correct identification of survivors. METHODS: A prolective observational study conducted in a single 850-bed hospital. Admission serum S100beta (S100B) and neuron-specific enolase (NSE) were determined for all adult survivors of non-traumatic out-of-hospital arrest and CPR. RESULTS: 158 patients were included, 126 (80%) died in hospital, 32 (20%) survived. Non-survivors had higher admission biomarker levels than survivors (p≤0.001 for both S100B and NSE). Presenting rhythm (VT/VF vs. other) and logarithmic-transformed S100B and NSE levels were statistically significant in the multivariable model predicting survival. The area under the model ROC curve was 0.868 (95%CI 0.80, 0.936). Plots for predicting survival for each combination of biomarker levels were generated for each sensitivity with and without VT/VF, allowing clinicians to select their option in terms of survival probability. In this modest-sized illustrative study the model misclassified 1/19 patients with Cerebral Performance Category 1-2 for sensitivity >0.80. CONCLUSIONS: We demonstrate how brain biomarkers can serve as decision support tools after CPR despite ethical/cultural differences in defining futility. Data from larger and diverse samples are required for stable estimates prior to clinical implementation of such a tool.

DHEA supplementation may improve IVF outcome in poor responders: a proposed mechanism.

OBJECTIVE: Dehydroepiandrosterone (DHEA) supplementation for poor responders may improve ovarian response and IVF treatment outcome. This study aimed to determine the mechanism of action of DHEA, and specifically, the stage of folliculogenesis influenced by DHEA. STUDY DESIGN: This is a prospective, self-controlled study of poor responders to IVF treatment, comparing day 3 biochemical (anti-Mullerian hormone (AMH), inhibin B and FSH) and ultrasound (antral follicle count (AFC)) ovarian reserve markers and IVF treatment outcome before and after DHEA supplementation of at least 3 months duration. RESULTS: Thirty-two women were included. Following DHEA, there was a significant increase in AFC (P=0.0003) without significant changes in the baseline biochemical parameters AMH, inhibin B, or FSH. The enhanced response comprised increased peak estradiol levels (P=0.0005), number of follicles >15 mm, oocytes, MII oocytes and embryos (P=0.004, P=0.00001, P=0.0004 and P=0.0006, respectively) and oocytes number/total FSH dose (P=0.0009). The proportion of cancelled cycles due to very poor response decreased significantly (P=0.02). CONCLUSIONS: DHEA does not appear to exert influence via recruitment of pre-antral or very small antral follicles (no change in AMH and inhibin B) but rather by rescue from atresia of small antral follicles (increased AFC).

Modeling serum biomarkers S100 beta and neuron-specific enolase as predictors of outcome after out-of-hospital cardiac arrest: an aid to clinical decision making.

OBJECTIVES: The aim of this study was to determine the added value of the serum biomarkers S100 and neuron-specific enolase to clinical characteristics for predicting outcome after out-of-hospital cardiac arrest. BACKGROUND: Serum S100 beta (S100B) and neuron-specific enolase concentrations rise after brain injury. METHODS: A prolective observational study was conducted among all adult survivors of nontraumatic out-of-hospital cardiac arrest admitted to 1 hospital (April 3, 2008 to April 3, 2011). Three blood samples (on arrival and on days 1 and 3) were drawn for biomarkers, contingent on survival. Follow-up continued until in-hospital death or discharge. Outcomes were defined as good (Cerebral Performance Category score 1 or 2) or poor (Cerebral performance category score 3 to 5). RESULTS: A total of 195 patients were included (65.6% men, mean age 73 ± 16 years), with presenting rhythms of asystole in 61.5% and ventricular tachycardia or ventricular fibrillation in 24.1%. Only 43 patients (22.0%) survived to hospital discharge, 26 (13.3%) with good outcomes. Patients with good outcomes had significantly lower S100B levels at all time points and lower neuron-specific enolase levels on days 1 and 3 compared with those with poor outcomes. Independent predictors at admission of a good outcome were younger age, a presenting rhythm of ventricular tachycardia or ventricular fibrillation, and lower S100B level. Predictors on day 3 were younger age and lower day 3 S100B level. The area under the receiver-operating characteristic curve of the admission-day model was 0.932 with and 0.880 without biomarker data (p = 0.027 for the difference). CONCLUSIONS: Risk stratification after out-of-hospital cardiac arrest using both clinical and biomarker data is feasible. The biomarkers, although adding an ostensibly modest 5.2% to the area under the receiver-operating characteristic curve, substantially reduced the level of uncertainty in decision making. Nevertheless, current biomarkers cannot replace societal considerations in determining acceptable levels of uncertainty. (Protein S100 Beta as a Predictor of Resuscitation Outcome; NCT00814814).

Quantitative neonatal glucose-6-phosphate dehydrogenase screening: distribution, reference values, and classification by phenotype.

OBJECTIVE: To determine enzyme assay reference values for newborns in a Sephardic Jewish population at high risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency. STUDY DESIGN: Quantitative G6PD testing was performed on umbilical cord blood. The reduction of nicotinamide adenine dinucleotide phosphate to nicotinamide adenine dinucleotide phosphate-oxidase, reflecting G6PD activity, was measured spectrophotometrically. Hemoglobin (Hb) was measured on the same sample. G6PD activity was recorded as U/g Hb. RESULTS: Males (N = 1502) were separated into 2 distinct groups: those <7 U/g Hb (n = 243 [16.2%], median 0.28 U/g Hb), designated G6PD deficient, presumably hemizygotes; and those ≥ 9 U/g Hb (n = 1256 [83.8%], 18.76 U/g Hb), designated G6PD normal, presumably hemizygotes. Female (n = 1298) values were a continuum and were categorized based on the male distribution: those <7 U/g Hb (n = 81 [6.2%], 4.84 U/g Hb), G6PD deficient, probably homozogytes; those ≥ 9.5 U/g Hb, equivalent to 50% of the male normal value, (n = 1153 (88.8%), 18.36 U/g Hb), G6PD normal, probably homozygotes; and those with intermediate values (n = 64 [4.9%], 8.61 U/g Hb), probable heterozygotes. CONCLUSIONS: Accurate identification of the male G6PD-deficient state was possible despite high normal neonatal G6PD values. Female values were presented as a continuum preventing accurate classification but were classified based on male phenotype for practical use.

B-type natriuretic peptides are reliable markers of cardiac strain in CKD pediatric patients.

Myocardial damage and strain are common in children with chronic renal failure. The most prevalent pathologies, as defined by echocardiography, are left ventricular hypertrophy (LVH), diastolic and systolic dysfunction, and altered LV geometry. Troponin I and T, as well as B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP, are known to be good markers of myocardial damage and stress, respectively, in the general adult population and among those with chronic kidney disease (CKD). In this study we measured the levels of troponins I and T, BNP, and NT-proBNP in a group of children and young adults with CKD stages 3-5 and determined their respective correlations with echocardiographic and laboratory abnormalities. BNP and NT-proBNP levels and their log values correlated well with the following parameters: diastolic blood pressure, estimated glomerular filtration rate, time-averaged hemoglobin levels, and LV mass. Both BNP and NT-proBNP levels, but not those of either troponin, were found to be reliable surrogate markers of strained hearts, defined as having LVH or diastolic or systolic dysfunction, in the pediatric CKD stages 3-4 group. The log NT-proBNP value was also found to be a good marker of cardiac strain in the CKD stage 5 group of patients. Serum BNP and NT-proBNP threshold concentrations of 43 and 529 pg/ml, respectively, were found to have the best sensitivity and specificity in predicting strained hearts. Based on these findings, we conclude that both BNP and NT-proBNP levels, but not those of troponins I and T, can serve as inexpensive, simple, and reliable markers of stressed hearts in the pediatric CKD patient population.

N-terminal pro B-type natriuretic peptide levels in infants and children with acute non-cardiac diseases.

BACKGROUND: Cardiac patients express elevated levels of B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP). However, there are non-cardiac causes of NT-proBNP level elevation. OBJECTIVES: To determine the upper limit of NT-proBNP for pediatric patients with acute non-cardiac disease. METHODS: We compared NT-proBNP concentrations in children with acute non-cardiac, mostly febrile disease with concentrations in children with acute cardiac disease and in healthy children. We used the Student t-test and Mann-Whitney test for group comparisons, and Pearson's and Spearman's correlation coefficients to test relationships between variables. RESULTS: In 138 patients with acute non-cardiac diseases (mean age 3.7 years, 53% male), median NT-proBNP concentration was 162 pg/ml, upper limit (95% percentile) 1049 pg/ml. The level did not vary significantly by disease category; was negatively correlated with weight, weight percentile, age and hemoglobin level; and positively correlated with creatinine level. Multivariant analysis showed weight to be the only factor influencing NT-proBNP level. Levels were higher in children with acute non-cardiac diseases versus healthy children (median 88 pg/ml, P < 0.001, n = 59), and lower than levels in patients with acute cardiac disease (median 29,986 pg/ml, P < 0.001, n=30). Receiver operating characteristic analysis showed good NT-proBNP performance for differentiation between children with acute cardiac versus non-cardiac disease (area under the curve 0.958), at a cutoff of 415 pg/ml. CONCLUSIONS: NT-proBNP levels are higher in children with acute non-cardiac diseases than in healthy children, but lower than in children with acute cardiac disease. NT-proBNP negatively correlated with weight and weight percentile.