Israel Medical Association Journal

Background: A pandemic (H1N1) influenza A virus was identified in 2009.

Objectives: To investigate predictors for pandemic (H1N1) 2009 virus infection among hospitalized patients with a flu-like illness and to identify parameters suggesting a severe clinical course.

Methods: We analyzed a cohort of all patients hospitalized during a 2 month period with a flu-like syndrome who were tested for pandemic (H1N1) 2009 infection. Demographic, clinical and laboratory, along with outcome parameters, were recorded and compared between pandemic (H1N1) 2009 virus-positive and negative hospitalized patients.

Results: Of the 179 examined hospitalized patients suspected of having pandemic (H1N1) 2009 infection 65 (36%) were found positive. These patients tended to be younger and had significantly fewer comorbidities. In addition, they had a significantly higher frequency of fever (94%), cough (86%) and myalgia (29%). Furthermore, age < 65 years and cough were independent predictors for pandemic (H1N1) 2009 virus positivity in a multivariate regression analysis. Notably, 14 of the 65 positive patients (21.5%) had acute respiratory insufficiency requiring treatment in the intensive care unit. These patients were neither older nor previously sicker than patients with non-severe disease, but were distinguished by augmented inflammatory markers, significant lymphopenia associated with disease severity, and overall mortality of 21.4%.

Conclusions: Pandemic (H1N1) 2009 virus-positive hospitalized patients tend to be younger and have fewer comorbidities as compared to compatible negative patients. A significant number of relatively young and previously healthy positive patients might develop severe disease associated with a robust inflammatory reaction and significant lymphopenia.

Background: Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative for APC gene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.

Objectives: To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol.

Methods: Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to ≥ 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC[1] patients fulfilling “Bethesda” (laboratory investigation) criteria for Lynch syndrome.

Results: Completion of APC gene exon 16 sequencing revealed one patient with the E1317Q polymorphism. All were normal by APC multiplex ligation-dependent probe amplification analysis. Pathogenic MUTYH mutations were found in three patients, all of North African origin; two additional patients had variants of unknown significance. One of six patients with Bethesda-positive criteria was MSI²-High with immunohistology consistent with MLH1 mutation.

Conclusions: Based on this small but well-characterized cohort with multiple colorectal adenomas, Lynch syndrome needs to be excluded if there are compatible criteria; otherwise MUTYH sequencing is probably the first step in evaluating APC-negative patients, especially for Jews of North African descent. Completing APC exon 16 sequencing and copy number variations analysis should probably be the last evaluations.

Background: Peritonitis is a major complication of chronic peritoneal dialysis therapy. It is recommended that each center monitor infection rates in order to define the local microbiological profile and implement an appropriate empiric antibiotic regimen.

Objectives: To analyze the microbiological profile of peritonitis in our pediatric dialysis unit and identify local predisposing factors.

Methods: In this retrospective study we reviewed the files of children treated with chronic PD[1] during the 10 year period 1997–2007.

Results: Eighty peritonitis episodes were recorded in 29 children (20 male, 9 female) aged 0.1–18.5 years (median 11.75) treated with peritoneal dialysis for 6–69 months (median 19) for a total of 578 patient-months. The annual peritonitis rate was 1.66/patient. The main pathogens were coagulase-negative Staphyloccocus (32.5%) and Pseudomonas spp. (16%), which were also cultured in most cases (64–69%) from the exit site during the 3 months preceding peritonitis. No peritonitis occurred in 31% of the patients (median age 12.5 years). All patients less than 5 years old had at least one peritonitis episode. Contaminating conditions (gastrostomy, enuresis, diaper use), found in 44% of the study group, and first infection within 6 months from starting PD were significantly associated with an increased peritonitis rate (P = 0.01, P = 0.009, respectively). Recurrent peritonitis led to a switch to hemodialysis in 18% of patients. There were no deaths.

Conclusions: The risk factors for peritonitis in our study were: first infection within less than 6 months from starting treatment, Pseudomonas exit-site colonization, and contaminating conditions (gastrostomies, diaper use, enuresis). These susceptible subgroups as well as very young age (< 5 years) at starting PD should be especially targeted during training of caregivers and follow-up to prevent later complications.  

[1] PD = peritoneal dialysis

Immunization coverage is a major health indicator. In Israel, routine childhood immunizations are provided at community public well-baby clinics. Immunization monitoring is an important cornerstone of a national health policy however, data obtained through sampling carries the risk of under-representation of certain population strata, particularly high risk groups. Despite high national average immunization coverage, specific sub-populations are under-immunized, as highlighted by outbreaks of vaccine-preventable diseases. The mean national immunization coverage at age 2 years (2006 data) was: DTaP[1]-IPV[2]-Hib4[3] (all 93%), HBV[4]3 (96%), MMR1[5] (94%), HAV1[6] (90%). These reports are based on a 17% population-based sample in some districts and on cumulative reports in others. A national immunization registry requires data completeness, protection of confidentiality, compulsory reporting by providers, and links to other computerized health records. It should provide individual immunization data from infancy to adulthood and be accessible to both providers and consumers. In 2008 the Israel Ministry of Health launched a national immunization registry based on immunization reporting from well-baby clinics using a web-based computerized system. As of January 2010, 120 well-baby clinics are connected to the nascent registry, which includes the records of some 50,000 children. The implementation of a comprehensive national immunization registry augurs well for the prospect of evidence-based assessment of the health status of children in Israel. 

 
[1] DTaP = diphtheria-tetanus-acellular pertussis

[2] IPV = inactivated polio vaccine

[3] Hib = Haemophilus influenzae b

[4] HBV = hepatitis B virus

[5] MMR = measles-mymps-rubella

[6] HAV = hepatitis B virus

Background: Obstruction of urine outflow can result from mechanical blockade as well as from functional defects. In adults, urinary tract obstruction is due mainly to acquired defects, such as pelvic tumors, calculi, and urethral stricture. In childhood it is mostly due to congenital malformations. In this article we present two rare cases of acute obstructive renal failure that presented with hydronephrosis. These cases underline the wide range of causes that may lead to this clinical feature. 

Background: Pathologic breast conditions are rare in childhood and adolescence. The spectrum of breast disease in the pediatric age group is different from that in adults, and most lesions are benign

Objectives: To describe the causes and characteristics of breast asymmetry in adolescents with normal endocrine profiles and sexual development.

Methods: The files of patients with a diagnosis of breast asymmetry referred to a tertiary pediatric center from 1990 to 2007 were reviewed for history and findings on physical examination with or without imaging, treatment and outcome.

Results: Eleven patients aged 12.5 to 18 years were identified. The cause of the breast asymmetry was traced to unpreventable medical factors in eight patients (physiologic, Poland anomaly, scleroderma), preventable/iatrogenic factors in two patients (chest tissue biopsy, thoracic drain), and possible combined medical-iatrogenic factors in one patient (scoliosis treated by a body brace). All patients were referred for breast reconstruction after full breast development.

Conclusions: Severe breast asymmetry in adolescence may be due to congenital factors, diseases involving the breast tissue, or to the effects of medical treatment, and may have severe adverse psychological and social implications. To prevent iatrogenic breast asymmetry, physicians should be made aware of the sensitivity of the breast tissue and should avoid unnecessary tests/procedures that involve the chest wall. In most cases a precise medical history and physical examination can differentiate between physiologic and non-physiologic causes.

Background: Streptococcus pneumoniae is now the predominant pathogen causing meningitis. The resistance of S. pneumoniae to penicillin and third-generation cephalosporins has grown steadily.

Objectives: To assess the antibiotic susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children with meningitis, and determine the antibiotic regimen appropriate for suspected bacterial meningitis in Israel.

Methods:  The study group included 31 children with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae isolates from the cerebrospinal fluid were tested for susceptibility to penicillin and ceftriaxone.

Results: Of the 35 isolates, 17 (48.6%) showed resistance to penicillin (minimum inhibitory concentration ≥ 0.12 µg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone (≥ 0.5 and < 2 μg/ml), and none showed complete resistance (MIC[1] ≥ 2 μg/ml). The rates of antibiotic resistance were higher in children who were treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P = 0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156).

Conclusions:  The rate of penicillin resistance is high in children with S. pneumoniae meningitis in Israel, especially in those treated with oral antibiotics prior to admission. Resistance to ceftriaxone is infrequent though not negligible. On the basis of these findings, current recommendations to empirically treat all children with suspected bacterial meningitis with ceftriaxone in addition to vancomycin until the bacterial susceptibility results become available are justified also in Israel.

Background: Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha.

Objectives: To test the hypothesis of the possible beneficial impact of IL-10[1] on mortality in systolic heart failure patients in relation to their circulating TNFα[2] levels.

Methods: We measured circulating levels of IL-10 and TNFα in 67 ambulatory systolic heart failure patients (age 65 ± 13 years).

Results: Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFα (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR[3] 3.67, 95% confidence interval 1.14–11.78).

Conclusions: Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFα had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.

Background: The incidence of congenital heart defects, reported to be 5–8/1000 in term infants, is not well established in very low birth weight infants.

Objectives: To establish the incidence of congenital heart defects in VLBW[1] infants in the neonatal intensive care unit of our institution.

Methods: A retrospective analysis of the population in the NICU[2] at our institution was performed. VLBW (BW ≤ 1500 g) infants born between 2001 and 2006 who survived more than 48 hours were included in the study. Infants with clinical signs of heart disease underwent echocardiography.

Results: During the study period 437 VLBW live-born infants met the inclusion criteria. Of these, 281 (64.3 %) underwent echocardiography. CHD[3] was detected in 19 infants (4.4%, 95% confidence interval 2.4–5.4%), significantly higher than the incidence of 5–8/1000 in the general population (P < 0.0001). In the subgroup of 154 infants with BW < 1000 g there were 10 (6.5%) with CHD. In the subgroup of 283 infants with BW 100–-1500 g there were 9 (3.2 %, P = 0.19 vs. VLBW) with CHD.

Conclusions:  Our observations show an increased incidence of CHD in VLBW neonates, as compared to the general population. Since not all infants underwent echocardiography, and minor cardiac defects may have been missed in our VLBW infants, the true incidence may be higher than reported here.

Background: Secondary thrombocytosis is associated with a variety of clinical conditions, one of which is lower respiratory tract infection. However, reports on thrombocytosis induced by viral infections are scarce.

Objectives: To assess the rate of thrombocytosis (platelet count > 500 x 10⁹/L) in hospitalized infants with bronchiolitis and to investigate its potential role as an early marker of respiratory syncytial virus infection.

Methods: Clinical data on 469 infants aged ≤ 4 months who were hospitalized for bronchiolitis were collected prospectively and compared between RSV[1]-positive and RSV-negative infants.

Results: The rate of thrombocytosis was significantly higher in RSV-positive than RSV-negative infants (41.3% vs. 29.2%, P = 0.031). The odds ratio of an infant with bronchiolitis and thrombocytosis to have a positive RSV infection compared to an infant with bronchiolitis and a normal platelet count was 1.7 (P = 0.023, 95% confidence interval 1.07–2.72). There was no significant difference in mean platelet count between the two groups.

Conclusions: RSV-positive bronchiolitis in hospitalized young infants is associated with thrombocytosis.

Lymphadenitis is the most common manifestation of non-tuberculous mycobacteria infection in children. Its frequency has increased over the past few decades. Diagnosis is based on clinical presentation, purified protein derivative skin test, and bacterial isolation. Management options are surgery, antibiotics, or "observation only"; however, the optimal therapy for this condition is still controversial.