Israel Medical Association Journal

Background: HER2 is an important prognostic and predictive marker in invasive breast cancer. It is currently assessed by immunohistochemistry for protein over-expression and by fluorescence in situ hybridization for gene amplification. The immunohistochemistry-equivocal cases (2+) are currently retested by FISH[1] to determine eligibility for trastuzumab treatment. Retesting by FISH significantly raises the cost of patient management and sometimes delays treatment. The 4B5 is a new, FDA-approved, rabbit monoclonal antibody for HER2 testing.

Objectives: To examine the reliability of 4B5 IHC[2] HER2 testing in cases found to be HER2 status equivocal by CB11 IHC.

Methods: Twenty-eight invasive breast cancer cases, with an equivocal HER2 status by CB11 IHC, were retested by the 4B5 antibody as well as by FISH analysis. The scoring was performed using the same guidelines as HercepTest and was correlated with the FISH ratio. Results: Of the original 28 CB11 clone designated equivocal cases, 14 (50%) showed negative HER2 staining using the 4B5 clone (HercepTest score 0 and 1+). Five cases (18%) proved to be positive (HercepTest score 3+) and 9 cases (32%) remained equivocal (HercepTest score 2+). The corresponding FISH ratio results showed that all 4B5 negative cases were negative by FISH testing, with a negative predictive value of 100% 4 of 5 of the 4B5-positive cases were positive by FISH testing, with a positive predictive value of 80%. One 4B5-positive case was borderline-high (2.2 ratio) by FISH. The correlation between 4B5 IHC and FISH was statistically significant (P = 0.0013) by chi-square test.

Conclusions: Sequential testing by 4B5 IHC could greatly reduce the need for FISH testing in cases considered HER2 equivocal by CB11 IHC.
 

 
[1] FISH = fluorescence in situ hybridization

[2] IHC = immunohistochemistry

Background: Ritual circumcision in neonates may cause a urinary tract infection within 2 weeks of the procedure.

Objectives: To evaluate the prevalence of urinary tract infection among Jewish male circumcised neonates (¡Ü 28 days old) evaluated for fever in the emergency room.

Methods: All available medical records of neonates presenting to the pediatric emergency room for evaluation of fever over a 10 year period were reviewed. Data included gender, ethnic background, age in days on presentation to the emergency room, age in days when circumcision was performed (in males ¡Ý 8 days of age), and results of urine, blood and cerebrospinal fluid cultures. Families of males older than 8 days of age who had a UTI[1] were contacted by telephone to verify the circumcision status when the infant presented to the ER[2], to ascertain whether the circumcision was performed ritually by a mohel* or by a physician, and, when not recorded in the chart, to verify the day of life on which circumcision was performed.

Results: Among neonates older than 8 days of age, 60 (24.7%) of the 243 febrile Jewish males had a UTI, as compared to 12 (8.4%) of 143 females (P < 0.0001). In 39 of 54 male neonates (72%) for whom circumcision was performed ritually on the eighth day of life, UTI occurred within 9 days of the circumcision. For females, there was no such clustering of UTI cases in the second week of life, nor during any other time period.

Conclusions: Febrile male neonates who have undergone ritual circumcision have a high prevalence of UTI and must be evaluated and treated accordingly. 

[1] UTI = urinary tract infection

[2] ER = emergency room

* Mohel is a Jewish man trained in the practice of Brit milah (circumcision).

Background: An outbreak of pertussis occurred in a daycare center with 87.5% vaccination coverage.

Objectives: To assess the effectiveness of the acellular pertussis vaccine and prevention of pertussis after chemoprophylaxis with azithromycin.

Methods: We studied 31 daycare children aged 3–5.5 years exposed to a child with pertussis. Nasopharyngeal swabs were obtained for Bordetella pertussis culture and polymerase chain reaction initially, and at days 21 and 60 of follow-up, in cases exhibiting symptoms.

Results: Of the 31 daycare children 6 (19%) tested positive for B. pertussis by PCR[1], 4 of whom had not been vaccinated against the disease. Of the two vaccinated children who contracted pertussis, one had milder symptoms and the other was asymptomatic. The incidence of pertussis was significantly lower in the vaccinated group (2/27) than in the unvaccinated group (4/4) (P = 0.000), with efficacy of the vaccine calculated to be 92.5%. Azithromycin chemoprophylaxis was taken only by 14 of the 25 exposed children (56%). On day 21 follow-up, there was no further laboratory-diagnosed B. pertussis cases in any of the exposed children, regardless of whether or not chemoprophylaxis was taken.

Conclusions: Based on the children’s clinical manifestations and PCR findings a pertussis outbreak had occurred in the daycare center studied. Our findings support the importance of pertussis vaccination since all the unvaccinated children in the daycare center contracted the infection.

Background: Hypocalcaemia following thyroid and parathyroid surgery is a well-recognized potential complication.

Objectives: To determine the utility of intraoperative quick parathormone assay in predicting severe hypocalcemia development following parathyroidectomy for a single-gland adenoma causing primary hyperparathyroidism.

Methods: A retrospective cohort study was performed. IO-QPTH[1] values were measured at time 0 (T0) before incision, and 10 (T10) and 30 minutes (T30) following excision of the hyperfunctioning gland. Percent decrease in IO-QPTH at 10 minutes (T10), maximum percent decrease of IO-QPTH value, and lowest actual IO-QPTH value obtained at surgery were used to determine any correlation with the development of postoperative hypocalcemia requiring treatment.

Results: Percent decrease in IO-QPTH at 10 minutes, maximum percent decrease in IO-QPTH and lowest IO-QPTH value did not correlate with the lowest postoperative calcium levels measured 18 hours after surgery (r = 0.017, P = 0.860 r = 0.018, P = 0.850 and r = 0.002, P = 0.985 respectively). For the purposes of our analysis, patients were subdivided into three groups. Group 1 comprised 68 patients with normal calcium levels (serum Ca 8.6¨C10.3 mg/dl) Group 2 had 28 patients with hypocalcemia (8.1¨C8.6 mg/dl) Group 3 included 12 patients with severe hypocalcemia (calcium level ¡Ü 8.0 mg/dl) requiring calcium supplementation due to symptoms of hypocalcemia. There was no difference between the three groups in the lowest IO-QPTH value (P = 0.378), percent decrease in IO-QPTH (P = 0.305) and maximum percent decrease in IO-QPTH (P = 0.142).

Conclusions: IO-QPTH evaluation was not useful in predicting the group of patients susceptible to develop severe postoperative hypocalcemia.  

[1] IO-QPTH = intraoperative quick parathormone

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: Severe hearing impairment can have devastating effects on social integration and vocational opportunities.

Objectives: To investigate how well – or poorly – individuals who underwent cochlear implantation as children integrated into the general Israeli hearing community.

Method: We sent a questionnaire to the 30 subjects ≥ 18 years old who underwent cochlear implants our department from 1990 to 2004 when they were < 18 years of age and had used their device for at least 3 years before replying.

Results: Eighteen implant users responded (14 males), yielding a 60% response rate. Their mean age was 13.3 ± 7.0 years (range 6–17) at implantation and 21.1 ± 3.6 years (range 18–34) when they filled in the questionnaire. Five were attending rabbinical school (yeshiva students), four were in regular military service, five were university students (three also held jobs), two were attending high school, one was employed (and had a university degree), and one had left the yeshiva and was unemployed when he returned the questionnaire. Fourteen respondents use the oral communication mode for conversation and the other 4 use both oral and sign languages. Longer daily implant use was significantly associated with coping with the difficulties in the setting in which they were currently active, with a higher level of satisfaction with their current lifestyle and with recognition of the implant’s contribution to this satisfaction (P = 0.037, P = 0.019 and P = 0.001, respectively).

Conclusions: Advances in cochlear implant technologies enable profoundly deaf implanted children to integrate well into the Israeli hearing society, albeit with a large inter-subject variability.