Israel Medical Association Journal

Background: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR[1] has emerged.

Objectives: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel.

Methods: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI[2] in four Israeli centers.

Results: Patients' mean age was 81.7 ± 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 ± 0.16 cm². The calculated mean logistic Euroscore was 19.3 ± 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 ± 13 to 9 ± 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 ± 0.6 at baseline to 1.4 ± 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients.

Conclusions: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Background: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ

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: Tubeless percutaneous nephrolithotomy is defined as PCNL[1] without postoperative nephrostomy tubes. It is reported to reduce postoperative pain, hospital stay and recovery time. To date the procedure has been reserved for selected patients.

Objectives: To assess our initial experience in extending the implementation of tubeless PCNL without preoperative patient selection.

Methods: All consecutive PCNLs performed during 2004–2008 were evaluated. Tubeless PCNL was performed when residual stones, bleeding and extravasation were excluded intraoperatively. Staghorn stones, stone burden, supracostal and multiple accesses, anatomic anomalies, solitary kidneys and operative time were not considered contraindications. We analyzed the clinical data and the choice of tubeless PCNL over time.

Results: Of 281 PCNLs performed during the study period, 200 (71%) were tubeless. The patients' average age was 53 years (range 28–82 years), the stone burden was 924 mm² (400–3150 mm²), operative time was 99 minutes (45–210 min), complication rate was 14% and immediate stone-free rate 91%. There were 81 conversions to standard PCNL (29%) due to expected second-look (n=47, 58%), impression of bleeding (n=21, 26%), suspected hydrothorax (n=7, 9%) and extravasation (n=6, 7%). The transfusion rate was 1%. The median hospital stay was 1 day (1–15 days) and recovery time 7 days (5–20 days). The rate of implementing the tubeless procedure increased steadily along time from 46% to 83% (P = 0.0001). 

Conclusions: Tubeless PCNL can be safely and effectively performed based on intraoperative decisions, without preoperative contraindications. They are easily accommodated by experienced endourologists and provide real advantages.

Background: Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN[1] is characterized by neutrophil count < 500 ml and a benign self-limiting course. Detecting specific antibodies against the polymorphic human neutrophil antigen usually confirms the diagnosis. Current available tests, however, are expensive and inapplicable in many laboratories as they require the use of isolated and fixed granulocytes obtained from donors pretyped for their distinct HNA[2] alloform.

Objectives: To assess the performance of a modified test to identify by FACS-analysis granulocyte-specific antibodies in the sera of neutropenic children.

Methods: We evaluated 120 children with a clinical suspicion of AIN, whose sera were analyzed by flow cytometry for the presence of autoantibodies using the indirect granulocyte immunofluorescence test. In contrast to the traditional tests, the sera were tested against randomly selected untyped neutrophils derived from a batch of 10 anonymous healthy subjects, presumably including the common HNA alloforms. Control sera samples were from patients with chemotherapy-induced, familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded.

Results: Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods.

Conclusions: The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective aiding tool for clinical decision making.

Background: Parallel to increased life expectancy, the number of very elderly patients hospitalized in internal medicine departments is growing rapidly, although clinical data on hospital care are lacking.

Objectives: To investigate the sociodemographic data, hospitalization characteristics and outcomes of nonagenarian patients, as these measures are necessary for evaluating prognostic information and predictors of mortality.

Methods: We reviewed the medical records of all patients aged ≥ 90 hospitalized in our institute's Department of Internal Medicine. The data comprised 482 admissions of 333 patients hospitalized over a one year period.

Results: Half of the study patients were residents of nursing institutions. A high rate of atrial fibrillation was documented (106 patients, 32%). Acute infectious diseases constituted the leading diagnosis (276/482 admissions, 57%), followed by acute coronary syndrome (17% of admissions). In-hospital mortality occurred in 74 patients (22%). Chronic therapy with statins or acetylsalicylic acid was inversely related to mortality (P < 0.05). The main predictors for in-hospital death of nonagenarians were pressure sores, older age, atrial fibrillation, malignant disease, and admission due to an acute infection, especially Clostridium difficile-associated diseases. In addition, mental decline, permanent urinary catheter, leukocytosis, renal failure and hypoalbuminemia predicted post-discharge mortality. Admission due to an infectious disease but not acute coronary syndrome was significantly correlated to in-hospital and post-discharge mortality (P < 0.001).

Conclusions: Hospitalized nonagenarians comprise a growing group with distinct characteristics and increasing significance in the daily practice of internal medicine departments. Comprehensive assessment of the elderly at admission together with identification of the above clinical and laboratory risk factors for mortality will help determine in-hospital management, discharge planning and rehabilitation programs.

Background: Stent thrombosis is a rare but devastating complication of coronary stent implantation. The incidence and potential predictors were assessed in a "real world” single center.

 Objectives: To examine whether socioeconomic status indeed affects the occurrence of stent thrombosis.

Methods: We searched our database for cases of "definite" stent thrombosis (according to the ARC Dublin definitions). Each case was matched by procedure date, age and gender; three cases of stenting did not result in stent thrombosis. Demographic and clinical parameters were compared and socioeconomic status was determined according to a standardized polling and market survey database.

Results: A total of 3401 patients underwent stent implantation in our hospital during the period 2004–2006. Their mean age was 63 ± 11 years, and 80% were males. Twenty-nine cases (0.85%) of “definite” sub-acute/late stent thrombosis were recorded. Mortality at 30 days was recorded in 1 patient (3.5%). Thrombosis occurred 2 days to 3 years after stent implantation. All patients presented with acute myocardial infarction. Premature clopidogrel discontinuation was reported in 60%. Patients with stent thrombosis had significantly higher rates of AMI[1] at the time of the initial procedure (76 vs. 32%, P < 0.001) and were cigarette smokers (60 vs. 28%, P < 0.001). Drug-eluting stents were used less in the stent thrombosis group. There was no difference in stent diameter or length between the two groups. Socioeconomic status was significantly lower at the stent thrombosis group, 3.4 ± 2.4 vs. 5.4 ± 2.6 (mean ± SD, scale 1–10, P < 0.01).

Conclusions: The incidence rate of stent thrombosis is at least 0.85% in our population. It appears in patients with significantly lower socioeconomic status and with certain clinical predictors. These results warrant stricter follow-up and support the policy of healthcare providers regarding patients at risk for stent thrombosis.

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Background: Intrapartum risk is based mainly on obstetric history, which is lacking in primiparous women.

Objectives: To ascertain whether the traditional known risk of primiparity is an independent variable for both maternal and neonatal outcome.

Methods: All women admitted to labor during March-April 2002 were canvassed for eligibility for participation in the study based on an obstetric risk scoring system developed and validated for our population. During the study period, 1473 women presented for delivery. Of these, 298 women (20%) were eligible according to the exclusion criteria as "low risk" parturients: 135 (45%) were primiparous and 163 (55%) were multiparous (2–5 births).

Results: After correction for significant confounding factors, primiparity was revealed as an independent significant risk factor for instrumental delivery (odds ratio 15.5, 95%confidence interval 1.88–125) and for early postpartum hemorrhage (OR[1] 5.6, 95%CI[2] 1.9–16.6).

Conclusions: This study highlights early postpartum hemorrhage as a significant risk for primiparous women, independent of mode of delivery, and also confirms previous reports of maternal complications requiring transfer from birth centers/home deliveries to tertiary centers.