Genotype-phenotype correlations in chronic granulomatous disease: insights from a large national cohort.

ABSTRACT: Neutrophils are the first line of defense against invading pathogens. Neutrophils execute and modulate immune responses by generating reactive oxygen species (ROS). Chronic granulomatous disease (CGD) is a primary immune deficiency disorder of phagocytes, caused by inherited mutations in the genes of the nicotinamide adenine dinucleotide phosphate reduced oxidase enzyme. These mutations lead to failure of ROS generation followed by recurrent bacterial and fungal infections, frequently associated with hyperinflammatory manifestations. We report a multicenter cumulative experience in diagnosing and treating patients with CGD. From 1986 to 2021, 2918 patients experiencing frequent infections were referred for neutrophil evaluation. Among them, 110 patients were diagnosed with CGD: 56 of Jewish ancestry, 48 of Arabic ancestry, and 6 of non-Jewish/non-Arabic ancestry. As opposed to other Western countries, the autosomal recessive (AR) CGD subtypes were predominant in Israel (71/110 patients). Thirty-nine patients had X-linked CGD, in most patients associated with severe infections (clinical severity score ≥3) and poor outcomes, presenting at a significantly earlier age than AR-CGD subtypes. The full spectrum of infections and hyperinflammatory manifestations is described. Six patients had hypomorphic mutations with significantly milder phenotype, clinical severity score ≤2, and better outcomes. Hematopoietic stem cell transplantation was implemented in 39 of 110 patients (35.5%). Successful engraftment was achieved in 92%, with 82% long-term survival and 71% full clinical recovery. CGD is a complex disorder requiring a multiprofessional team. Early identification of the genetic mutation is essential for prompt diagnosis, suitable management, and prevention.

Skull Base Osteomyelitis in Children: Clinical Characteristics and Potential Implications.

OBJECTIVES: We describe 10 new cases of otogenic (n = 8) and nonotogenic (n = 2) skull base osteomyelitis (SBO) in previously healthy children and review the literature on SBO in the pediatric population. METHODS: We retrospectively analyzed the medical records of 10 children (age range 0.9-12.8 years) discharged with a diagnosis of SBO between 2015 and 2020 in 2 children's hospitals in central Israel. RESULTS: Five patients presented with fever and 5 with otological signs and symptoms. All 10 children underwent a comprehensive clinical evaluation, imaging studies (computerized tomography or magnetic resonance imaging) and laboratory investigations. The physical examination revealed neurologic findings, including nuchal rigidity, papilledema, and apathy, in 4 patients. All 8 otogenic patients underwent surgical intervention and the 2 nonotogenic patients, who were diagnosed as having deep neck and throat infections, responded well to treatment consisting of antibiotics without surgery. CONCLUSIONS: Early diagnosis of pediatric SBO can be challenging because the symptoms are often nonspecific. The final diagnosis relies mainly on imaging, preferably magnetic resonance imaging. Surgical intervention is usually mandatory in the otogenic patients, whereas the nonotogenic patients respond well to medical management alone.

Pott's Puffy Tumor in Pediatric Patients: Case Series and Literature Review.

BACKGROUND: Pott's puffy tumor (PPT) is a rare complication of frontal sinusitis. Although it may occur at any age, the incidence is higher during adolescence. METHODS: We report a series of 10 pediatric patients (9-17 years of age) who presented with PPT in 2 tertiary care pediatric hospitals in central Israel between January 2018 and August 2022 and review the published literature on pediatric PPT. RESULTS: The most common clinical presentations included headache (10 cases), frontal swelling (6 cases) and fever (5 cases). Symptom duration before admission was between 1 and 28 days (median 10 days). The diagnosis of PPT was made by imaging studies at a median of 1 day after admission. All 10 patients underwent computed tomography studies, and 6 patients also underwent magnetic resonance imaging. The overall rate of intracranial complications was 70%. All 10 children were treated with systemic antibiotics and surgical interventions. Streptococcus constellatus group was the most common causal bacteria. All 10 patients recovered uneventfully. CONCLUSIONS: Our findings show that a high index of suspicion for PPT should be applied to adolescents presenting with prolonged headache and frontal swelling. Contrast-enhanced computed tomography is an appropriate first tool for the evaluation; however, an magnetic resonance imaging should be performed to determine the necessity of intracranial interventional treatments if there is any suspicion of intracranial involvement. Complete recovery can be expected with appropriate antibiotic treatment and surgical intervention in most of the cases.

Revaccination of children with acute lymphoblastic leukemia following completion of chemotherapy.

BACKGROUND: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy. METHODS: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination. RESULTS: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster. CONCLUSIONS: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated.

Impact of COVID-19 Pandemic on Human Papillomavirus Vaccine Uptake in Israel.

OBJECTIVE: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic. METHODS: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure. RESULTS: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia. CONCLUSIONS: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics.

Flavobacteriaceae Bacteremia in Children: A Multicenter Study.

BACKGROUND: The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections. METHODS: A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018. RESULTS: Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days-17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin. CONCLUSIONS: C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.

A Case of Methotrexate Neurotoxicity Presented as Status Epilepticus, Encephalopathy, and High Fever.

High-dose methotrexate is used to treat a range of adult and childhood cancers including osteosarcoma. Significant neurotoxicity is reported in 1% to 4.5% of patients treated with high-dose methotrexate and can present in a wide variety of symptoms. We present a case of a 14-year-old boy with a recent diagnosis of osteosarcoma who presented to the emergency department with status epilepticus, altered mental status, and very high fever secondary to methotrexate neurotoxicity. We review current literature and discuss some controversies related to this state. We also describe high fever as one of the possible symptoms associated with this condition and suggest using specific magnetic resonance imaging sequence to uncover abnormal findings related to this state. Since high-dose methotrexate is not a rare treatment in this era, we believe that in addition to oncologists, emergency department and intensive care providers should be aware of the potential role of methotrexate in causing significant neurotoxicity and include it in the differential diagnosis when treating a patient presenting with new neurological symptoms in the setting of recent high-dose methotrexate treatment.

The value of cerebrospinal fluid lactate levels in diagnosing CSF infections in pediatric neurosurgical patients.

PURPOSE: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children. METHODS: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele). RESULTS: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF. CONCLUSIONS: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

Risk factors and epidemiology of pediatric ventriculoperitoneal shunt infection.

BACKGROUND: The aim of this study was to identify independent risk factors for cerebrospinal fluid shunt infection. METHODS: The medical records of all patients aged 0-18 years who underwent shunt-related surgery for the treatment of hydrocephalus at the present institution between January 1996 and December 2015 were reviewed. For each case, two randomly selected controls with no shunt infection, matched for year of surgery, were chosen. Demographic clinical and microbiological data were abstracted. RESULTS: A total of 1,570 shunt-related procedures met the inclusion criteria, yielding 68 infections (in 63 patients). The control group consisted of 132 infection-free patients. The average annual infection rate was 4.2% cases per year. The median time between shunt procedures to infection was 19 days (range, 1-2,181). On multivariate analysis, risk factors associated with increased risk for developing an infection included a history of two or more previous revisions (OR, 4.8; 95%CI: 1.5-15.9); and age <5 years (OR, 4.5; 95%CI 1.5-13.4). A neoplastic etiology for hydrocephalus was found to be a protective factor for shunt infection (P = 0.001). CONCLUSIONS: A history of shunt revision was the most significant risk factor in the development of subsequent shunt infection. Age >5 years was a protective factor. Future efforts should focus on modalities to optimize revision procedures and reduce the risk of subsequent infection.

Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A).

PURPOSE: Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47phox deficiency. METHODS: Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47phox by immunoblotting and molecular confirmation by DNA sequence analysis. RESULTS: Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47phox deficiency. CONCLUSIONS: Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.

Lessons From an Outbreak of Varicella Infection in Pediatric Hemato-oncology Patients.

BACKGROUND: Immunocompromised patients exposed to varicella may experience significant morbidity and a 7% mortality rate. Management and outcome of an outbreak of varicella infection among hospitalized pediatric hemato-oncology patients using the guidelines of the American Academy of Pediatrics Committee on Infectious Diseases are presented. METHODS: This retrospective study describes an outbreak of varicella infection between February 2011 and June 2011. Data were retrieved from the patients' files. Positive polymerase chain reaction results for varicella zoster virus from vesicular skin lesions were used for the diagnosis of varicella infection. RESULTS: Twelve pediatric hemato-oncology patients experienced 13 episodes of varicella infection, 11 underwent 1 episode each and 1 patient had 2 episodes. All exposed patients without immunity received varicella zoster immune globulins or intravenous immunoglobulin and were isolated as recommended by the guidelines. Infected patients received intravenous acyclovir. One patient with acute lymphoblastic leukemia at induction chemotherapy died. All the other patients survived. CONCLUSIONS: Our experience in the management of hospitalized immunocompromised patients exposed to varicella was that a positive IgG serology did not confer protection after exposure to varicella infection and thus can not serve as a marker for immunity. Unlike the isolation period sufficient for immunocompetent patients, crusted lesions can be contagious and thus require extended isolation for immunocompromised patients. Patients receiving rituximab are at greater risk of having persistent or recurrent disease. Studies with a larger sample size should be performed to better assess the management of immunocompromized patients exposed to varicella.

Chronic Q Fever Infections in Israeli Children: A 25-year Nationwide Study.

BACKGROUND: Q fever is a zoonosis caused by the bacterium Coxiella burnetii (C. burnetii) with a worldwide distribution. Our aim was to assess the epidemiology, clinical manifestations and treatment regimens of chronic Q fever infections in Israeli children during the past 25 years. METHODS: Cases were collected from the national Q fever reference laboratory database. Demographic, epidemiologic and clinical data were reviewed using a structured questionnaire sent to the referring physician. Cases were defined according to the new Dutch Consensus Guidelines. RESULTS: A total of 16 children originating from all regions of the country were found positive for chronic Q fever infections. The most common infection site was bone or joint (8/16, 50%), all in previously healthy children. Endovascular infections were found in 5 children (31%), all with an antecedent cardiac graft insertion. According to the new Consensus Guidelines, 9 children (56%) had a proven infection, 3 (19%) a probable infection and 4 (25%) a possible chronic Q fever infection. Almost all cases were treated with a long-term antibiotic regimen, often necessitating a change in medication because of persistent or rising titers. CONCLUSIONS: Although pediatric chronic Q fever infections are rare, incidence has been rising. The most common infection site was bone or joint. A high index of suspicion is necessary, even in cases of previously healthy children without a possible exposure history. Use of the relatively new diagnostic tools in combination with serologic methods is helpful in diagnosing proven cases. There is no consensus as to the selection or duration of antibiotic treatment.

Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients.

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc.

Severe Acute Mastoiditis Admission is Not Related to Delayed Antibiotic Treatment for Antecedent Acute Otitis Media.

BACKGROUND: Delayed antibiotic treatment for acute otitis media (AOM) is recommended for children >6 months with nonsevere illness, no risk factors for complications or history of recurrent AOM. This study evaluates relationship between delayed antibiotic treatment for antecedent AOM and severity of subsequent acute mastoiditis admission. METHODS: A prospective observational study of children aged 0-14 years admitted with acute mastoiditis to 8 hospitals between 2007 and 2012 calculates rates of severe acute mastoiditis admission [defined by ≥1 of the following: complication (mastoid subperiosteal abscess, brain abscess and sagittal vein thrombosis), need for surgical procedure and duration of admission >6 days].Severe acute mastoiditis admissions in children with antecedent AOM treated with immediate antibiotics were compared with those with delayed antibiotic treatment. RESULTS: Antecedent AOM was diagnosed in 216 of 512 acute mastoiditis admissions (42.1%), of whom 159 (73%) immediately received antibiotics, and 57 (27%) had delayed antibiotic treatment. Higher rate of recurrent AOM was noted in the immediate compared with delayed antibiotic treatment group (29% vs. 8.7%, P = 0.0021). Complication rates were 19.5% versus 10.5% (P = 0.12), rates of surgical procedures required, 30% versus 10% (P = 0.0033); admission rates >6 days, 37% versus 29% (P = 0.28) for immediate antibiotic therapy and delayed antibiotic treatment. On logistic regression analysis, immediately treated AOM patients had increased need for surgery for acute mastoiditis with adjustment for history of recurrent AOM (relative risk: 3.2, 95% confidence interval: 1.4-7.0). CONCLUSIONS: Delayed antibiotic treatment for antecedent AOM is not associated with an increase in severity parameters in subsequent acute mastoiditis admission.

Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency.

Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive genetic disorder of the purine salvage pathway, associated with a variable extent of immunodeficiency. Here, we report a PNP-deficient patient who presented early in life with clinical and laboratory characteristics of severe combined immunodeficiency, including severe infections, marked T-and B-cell deficiency, lack of lymphocyte response to mitogenic stimulation, monoclonal T-cell receptors representation and the absence of T-cell receptor excision circles and Kappa-receptor excision circles. The patient carried homozygote mutation at the PNP gene that putatively led to aberrant splicing, allowing normal and abnormally spliced products from the mutant alleles. We suggest that the aberrant slice site was used preferentially over the normal slice site in some cells correlating with the severity of disease.

Retropharyngeal and parapharyngeal abscess in children--epidemiology, clinical features and treatment.

OBJECTIVE: To describe the clinical presentation, diagnosis, management and complications of children with retropharyngeal abscesses (RPAs) and parapharyngeal abscesses (PPAs). METHODS: A retrospective chart review was conducted at two tertiary care, pediatric hospitals in Israel. The medical records of all children <18 years who had been admitted with a diagnosis of RPA or PPA during an 11-year period (January 1997 to February 2008) were reviewed. Data on demographics, presenting symptoms, physical examination findings, imaging studies and interpretation, laboratory results, hospital course, medical treatment and surgical interventions were retrieved. RESULTS: A total of 39 children were diagnosed as having RPA (n=26, 67%) or PPA (n=13, 33%). There was a predominance of boys (61.5%). The mean age of all the children at diagnosis was 4 years. The annual incidence increased over the 11-year period. The most common symptoms at presentation included fever (n=27, 70%) and neck pain (n=24, 62%). The physical examination revealed cervical lymphadenopathy in 30 children (77%), limitation of neck movements in 25 (64%), torticollis in 21 (54%), drooling in three (8%), and stridor in two (5%). Computerized tomographic (CT) scanning with contrast was performed in 37 patients (95%), of whom 17 underwent surgical drainage. Thirteen children were positively diagnosed as having an abscess by the finding of pus at surgery, of whom 12 had been found to have an abscess on their CT scan. All the patients received intravenous antibiotics. There was no significant difference in the duration of hospital stay between those who underwent surgery and those who were treated with antibiotics alone. There were no treatment failures and no complications in either of the two groups. CONCLUSION: Children with RPA most commonly present with restricted neck movements, fever and cervical lymphadenopathy, and rarely with respiratory distress or stridor. Many patients with RPA and PPA can be treated successfully without surgery. CT scans are helpful in diagnosing and assessing the extent of the infection, but they are not always accurate.

Nosocomial infections in pediatric cardiovascular surgery patients: a 4-year survey.

OBJECTIVE: To determine the prevalence, characteristics, and risk factors for nosocomial infections (NIs) in children postcardiac surgery and hospitalized in a pediatric intensive care unit (PICU). DESIGN: Case control study. SETTING: PICU of a tertiary care university-affiliated medical center. PATIENTS AND CONTROLS: Between January 1, 1999 and December 31, 2002, 356 children underwent cardiac surgery and were admitted to the PICU (381 admissions). There were 146 episodes (91 patients) of NI according to the Centers for Disease Control and Prevention criteria. The control group (92 patients) was drawn as a random sample from admissions with no evidence of NI. MEASUREMENTS AND MAIN RESULTS: Data retrieved from medical records included demographic information, type of operation, complexity score, extrinsic risk factors (invasive devices, postoperative complications, etc.), specific pathogens, therapeutic interventions, and outcome. There were 146 episodes of NI during 381 admissions, yielding a nosocomial infection ratio of 38.3%, and a prevalence of PICU-acquired infection of 24.4% (93 admissions with NI out of a total of 381 admissions). The most common NI sites were the bloodstream and the lower respiratory tract (65.8% and 16.4%, respectively). The main causative organisms were Coagulase negative Staphylococcus, Klebsiella pneumonia, and Candida spp. (18.8%, 16.7%, and 15%, respectively). Multivariate analysis revealed the following risk factors for NI: age < 2 months, congenital malformations, post operative complications, and open-chest procedure. The crude mortality rate for patients with NI was 23.7%, compared with 2.2% for patients without NI (p < 0.001). Predictors for mortality in patients with NI were post operative complications, open-chest procedure, sepsis, and urinary tract infection. CONCLUSIONS: Our results draw attention to the importance of NI and their influence on survival in pediatric patients undergoing cardiac surgery. Prevention and control measures may reduce these infections and subsequently reduce morbidity and mortality in this vulnerable population.

Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients.

Chronic granulomatous disease (CGD) is an innate immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. In the course of 21 years, 38 Israeli CGD patients were diagnosed with 17 gene mutations, seven of which were new. Clinical, functional, and molecular studies were accomplished. Although X-linked recessive (XLR)-CGD is worldwide the most common genotype of the disease (~70%), in our study only 11 patients (29%) suffered from XLR-CGD. In Israel, the higher incidence of the autosomal recessive (AR) form of CGD (63%) may be related to consanguineous marriages. In three patients (8%), all four proteins of the NADPH oxidase were present. Severe clinical expression was found both in the XLR and AR forms, but in general a milder disease was evident in AR-CGD, particularly in patients with p47(phox) deficiency. Despite early and aggressive therapy, a mortality rate of 26% was noted. Given that bone-marrow transplantation was successful in five of seven patients, it is recommended to perform it as early as possible before tissue damage is irreversible.

Multicenter cross-sectional study of nontuberculous mycobacterial infections among cystic fibrosis patients, Israel.

This 2-year cross-sectional evaluation of nontuberculous mycobacterial (NTM) infections involved all Israeli medical centers that treat cystic fibrosis patients. The study comprised 186 patients whose sputum was analyzed for NTM. The prevalence of NTM isolates was 22.6%, and 6.5% and 10.8% of the patients fulfilled the 1997 and 2007 American Thoracic Society criteria for NTM lung disease, respectively. Mycobacterium simiae (40.5%), M. abscessus (31.0%), and M. avium complex (14.3%) were the most prevalent. Presence of Aspergillus spp. in sputum and the number of sputum specimens processed for mycobacteria were the most significant predictors for isolation of NTM (odds ratio [OR] = 5.14, 95% confidence interval [CI] 1.87-14.11 and OR = 1.47, 95% CI 1.17-1.85, respectively). The incidence of NTM pulmonary infections is increasing among cystic fibrosis patients, reflecting the increase in longevity of such patients as well as environmental exposure to various species of mycobacteria.