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: Guidelines are frequently under-implemented in older patients with heart failure. Octogenerians are often excluded from clinical trials.

Objectives: To characterize the clinical profile of the oldest-old (age ≥ 80 years) heart failure patients hospitalized in a subacute geriatric hospital and to evaluate their management and 1 year outcome.

Methods: Patient characteristics and in-hospital course were retrospectively collected. Diagnosis of heart failure was based mainly on clinical evaluation in addition to chest X-ray results and echocardiographic findings when available.

Results: The study population comprised 96 consecutive unselected heart failure patients hospitalized from January to June 2003. The patients were predominantly women (67%), aged 85 ± 5 years, fully dependent or frail with a high rate of comorbidities. Adherence to guidelines and recommended heart failure medications was poor. Their 1 year mortality was 57%. According to logistic regression analysis, predictors of 1 year mortality were lower body mass index (odds ratio 0.86, 95% confidence interval 0.78–0.96) and high urea levels (OR[1] 1.04, 95% CI[2] 1.02–1.06).

Conclusions: Our study confirms that the management of oldest-old heart failure patients hospitalized in a subacute geriatric hospital was suboptimal and their mortality was exceptionally high.

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: 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: Chronic heart failure is associated with excessive hospitalizations and poor prognosis.

Objectives: To summarize the 5 year experience of a single-center CHF[1] day care service, detect the cardiovascular and non-cardiovascular events, and evaluate the safety of the treatments provided.

Methods: We retrospectively studied all patients admitted to the CHF day care service of the Sheba Medical Center between September 2000 and September 2005.

Results: Advanced (New York Heart Association class III-IV) CHF patients (n=190), mean age 65 ± 12 years and left ventricular ejection fraction 25 ± 11%, were treated for 6 hourly biweekly visits; 77% had ischemic and 23% had non-ischemic cardiomyopathy. Treatment included: intravenous diuretic combinations (91%), intermittent low dose (≤ 5 mg/kg/min) dobutamine (87%), low dose (≤ 3 mg/kg/min) dopamine (38%), intravenous iron preparation and/or blood (47%), and intravenous nitropruside (36%). Follow-up of at least 1 year from initiation of therapy was completed in 158 of 190 patients (83%). Forty-six (29.3%) died: 23% due to CHF exacerbation, 5.7% from infection, 4.4% from sudden cardiac death, 3.8% from malignancy, 2.5% from malignant arrhythmias, 1.9% from renal failure, 1.3% from stroke, and 0.6% from myocardial infarction. There were only 0.68 rehospitalizations/patient/year; the most frequent cause being CHF exacerbation (16.5%).

Conclusions: Our study demonstrates the safety and potential benefits of a supportive day care service for advanced CHF patients. Multidrug intravenous treatment, accompanied by monitoring of electrolytes, hemoglobin and cardiac rhythm, along with education and psychological support, appear to reduce morbidity in advanced CHF patients and may have contributed to the lower than expected mortality/hospitalization rate.

Background: Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University ocular oncology clinic has become a referral center for uveal melanoma patients.

Objectives: To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988–2007.

Methods: Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software.

Results: Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 ± 7.1 new cases per year (mean ± standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 ± 16.5 years (range 5–95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma.

Conclusions: Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Background: Syncope is a common clinical problem that often remains undiagnosed despite extensive and expensive diagnostic evaluation.

Objectives: To assess the diagnostic evaluation, costs and prognosis of patients hospitalized for syncope in a tertiary referral center according to discharge diagnosis.

Methods: We retrospectively reviewed the medical records of patients with a diagnosis of syncope discharged from a tertiary referral center in 1999. In addition, mortality data were obtained retrospectively a year after discharge for each patient.

Results: The study group comprised 376 patients. Discharge etiologies were as follows: vasovagal 26.6%, cardiac 17.3%, neurological 4.3%, metabolic 0.5%, unexplained 47.3%, and other 4%. A total of 345 patients were admitted to the internal medicine department, 28 to the intensive cardiac care unit, and 3 to the neurology department. Cardiac and neurological tests were performed more often than other tests, with a higher yield in patients with cardiac and neurological etiologies respectively. The mean evaluation cost was 11,210 ± 8133 shekels, and was higher in the ICCU[1] than in internal medicine wards (19,210 ± 11,855 vs. 10,443 ± 7314 shekels, respectively; P = 0.0015). Mean in-hospital stay was 4.9 ± 4.2 days, which was longer in the ICCU than in medicine wards (7.2 ± 5.6 vs. 4.6 ± 3.5 days, respectively; P = 0.024). Short-term mortality rates (30 days after discharge) and long-term mortality rates (1 year after discharge) were 1.9% and 8.8% respectively, and differed according to discharge etiology. LTM[2] rates were significantly higher in patients discharged with cardiac, neurological and unknown etiologies (not for vasovagal), compared with the general population of Israel (1 year mortality rate for the age-adjusted [65 years] general population = 2.2%). The LTM rate was higher in patients discharged with a cardiac etiology than in those with a non-cardiac etiology (15.4% vs. 7.4%, P = 0.04). Higher short and long-term mortality rates were associated with higher evaluation costs.

Conclusions: Hospitalization in a tertiary referral center for syncope is associated with increased mortality for most etiologies (except vasovagal), cardiac more than non-cardiac. Despite high costs of inpatient evaluation, associated with more diagnostic tests, longer in-hospital stay and higher mortality rates, nearly half of the patients were discharged undiagnosed. Outpatient evaluation should be considered when medically possible.

Background: Despite improved management of heart failure patients, their prognosis remains poor.

Objectives: To characterize hospitalized HF[1] patients and to identify factors that may affect their short and long-term outcome in a national prospective survey.

Methods: We recorded stages B-D according to the American College of Cardiology/American Heart Association definition of HF patients hospitalized in internal medicine and cardiology departments in all 25 public hospitals in Israel.

Results: During March-April 2003, 4102 consecutive patients were recorded. Their mean age was 73 ± 12 years and 57% were males; 75.3% were hypertensive, 50% diabetic and 59% dyslipidemic; 82% had coronary artery disease, 33% atrial fibrillation, 41% renal failure (creatinine ³ 1.5 mg/dl), and 49% anemia (hemoglobin £ 12 g/dl). Mortality rates were 4.7% in-hospital, 7.6% at 30 days, 18.7% at 6 months and 28.1% at 12 months. Multiple logistic regression analysis revealed that increased 1 year mortality rate was associated with New York Heart Association III–IV (odds ratio 2.07, 95% confidence interval 1.78–2.41), age (for 10 year increment) (OR[2] 1.41, 95% CI[3] 1.31–1.52), renal failure (1.79, 1.53–2.09), anemia (1.50, 1.29–1.75), stroke (1.50, 1.21–1.85), chronic obstructive pulmonary disease (1.25, 1.04–1.50) and atrial fibrillation (1.20, 1.02–1.40).

Conclusions: This nationwide heart failure survey indicates a high risk of long-term mortality and the urgent need for the development of more effective management strategies for patients with heart failure discharged from hospitals.

Background: Left ventricular outflow gradient is associated with increased morbidity and mortality in hypertrophic cardiomyopathy. Alcohol septal ablation is the alternative to surgery in cases refractory to drug therapy. The implication of LVOG[1] measured 1 week post-ASA[2] for prediction of outcome is unknown.

Objective: To observe the pattern of LVOG course and prediction of long-term clinical and hemodynamic outcome of ASA.

Methods: Baseline clinical and echocardiographic parameters were prospectively recorded in 14 consecutive patients with a first ASA, at the time of ASA, 3 and 7 days after ASA (in-hospital) and 3 and ≥ 12 months after ASA (last follow-up).

Results: There was improvement in NYHA class, exercise parameters and LVOG in 11 of 14 patients (P < 0.005 in all). Maximal creatine kinase level was lower than 500 U/L in those without such improvement and 850 U/L or higher in successful cases. LVOG dropped from 79 ± 30 to 19 ± 6 mmHg after the ASA. LVOG was 50 ± 21 mmHg on day 3, 39 ± 26 on day 7, 32 ± 26 at 3 months and 24 ± 20 mmHg at last follow-up. LVOG identified 27% sustained procedural successes on day 3 and 73% on day 7. The overall predictive accuracy of the test for sustained success and failure was 36% on day 3 and 71% on day 7. Combination of maximal CK[3] and LVOG on day 7 showed four distinct outcome patterns: "early success" with low LVOG and high CK (73% of successful cases), "late success" with high LVOG and high CK, and "early failure" and "late failure" with both low CK and high or low LVOG, respectively
Conclusion: LVOG measurement 7 days post-ASA combined with maximal CK levels predicts late procedural outcome in the majority of patients

Objective: To investigate gender differences in the baseline characteristics, clinical presentation, treatment and prognosis of women with unstable angina.

Method: Data were collected prospectively as part of the Acute Coronary Syndromes Israeli Survey in 2000 at Soroka University Medical Center. In-hospital management and 2 year follow-up were monitored for 226 consecutive patients with unstable angina admitted to our medical center during February and March 2000.

Results: Women were older (71 ± 12 vs. 66 ± 12, P = 0.006), more diabetic (41.3% vs. 34.5%, not significant) and hypertensive (76.3% vs. 64.6%, P = 0.07). Women presented more often with atypical chest pain (18.8% vs. 7.5%, P = 0.038). Heparin, aspirin and angiotensin-converting enzyme inhibitor were equally delivered, but more beta-blockers were administered to women (88.5% vs. 75.7%, P = 0.02) and more statins to men (48.1% vs. 35.4%, P = 0.07). Angiography rates were similar (17.7% vs. 19.6%). Similar management was documented during the 2 year follow-up. Re-hospitalization rates were similar (53.3% of women and 63.7% of men, NS). Men had a tendency to develop acute myocardial infarction more often (9.6% vs. 2.7%, P = 0.06) and to develop peripheral vascular disease (3.7% vs. 0%, P = 0.09), and they had a non-significant higher rate of coronary artery bypass graft (6.7% vs. 1.3%, P = 0.08). No gender difference was found in angiography (14.7% of women vs. 16.3% of men) or percutaneous intervention (13% vs. 16.7%). At 2 years there was no gender-related difference in mortality (13.3% of women vs. 16.3% of men, NS). Kaplan-Meier analysis for event-free survival after 2 years showed no gender difference in survival. Multi-regression analysis showed that gender was not a prognostic factor for survival.

Conclusions. We found no major difference in the management of men and women with unstable angina. Although men showed a tendency to suffer more major cardiac events, their 2 year prognosis was the same as for women.