Israel Medical Association Journal

Background: Little is known of the outcome of pregnant patients with previously diagnosed dilated cardiomyopathy. These patients are usually firmly advised against continuation of the pregnancy.

Objectives: To examine the usefulness of serial echocardiographic follow-up and plasma N-terminal pro-B type natriuretic peptide levels in the management of pregnant women with preexisting DCM[1].

Methods: We prospectively enrolled pregnant women with DCM either known or diagnosed in the first trimester. Clinical examination and serial echocardiography studies at baseline, 30 weeks gestation, peripartum, and 3 and 18 months postpartum were performed. Blinded NTproBNP[2] levels were obtained at 30 weeks, delivery and 3 months postpartum.

Results: Between June 2005 and October 2006 we enrolled seven women who fulfilled the study criteria. Delivery and postpartum were complicated in 3 patients (42%): 2 with acute heart failure, which resolved conservatively, and 1 with major pulmonary embolism. The left ventricular ejection fraction was stable throughout the pregnancy (35% ± 2.8 at baseline, 33% ± 2.9 at 30 weeks) and postpartum (35% ± 2.8 at 1 day, 34% ± 3.1 at 90 days). Similar stable behavior was observed regarding left ventricular dimensions: LV[3] end-systolic diameters 43.3 ± 2.7 mm and LV end-diastolic diameters 57.3 ± 3.3 mm at baseline compared with 44.1 ± 3.1 mm and 58.7 ± 3.1 mm postpartum, respectively. The NT-ProBNP levels rose significantly peripartum in all three patients with complications.

Conclusions: Serial NT-proBNP levels, as compared to echocardiography, may be a better clinical tool in monitoring and management of pregnant women with preexisting DCM. An early rise in NT-ProBNP level appears to predict the occurrence of adverse events.

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.

The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases – such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas – considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is typically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities require prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST[1] refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.

Background: Professional volunteers play a crucial role in reinforcing emergency medical services in Israel. In order to encourage volunteers to return for additional shifts, the organization should provide conditions that will assure the return, particularly at a time of self-risk such as war. In 2009 Israeli emergency medical services (Magen David Adom) were required to increase preparedness in the southern part of the country due to missile attacks on civilian populations, while continuing their routine activities, i.e., responding promptly to emergency events. In order to perform these multiple functions, MDA[1] stations in the towns under attack were strengthened with volunteers from other regions of the country. These volunteers, trained as paramedics, served in 24–48 hour shifts.

Objectives: To identify the factors influencing the willingness of volunteers to return.

Methods: A questionnaire was used to assess the satisfaction of volunteers participating in the reinforcement with regard to their physical environment, job assignment and the actual activity they were involved in. Data were analyzed using SPSS statistical software.

Results: During the 10 days of the study, 121 volunteers reinforced southern MDA stations and 99 (81%) of them responded to the questionnaire. We found that volunteers' willingness to return to do more shifts was affected by their welcome and reception at the station, their job assignment, and their training and preparation for performing the necessary tasks. The sleeping conditions and the number of events they participated in were also contributing factors.

Conclusions: Factors that contribute to the willingness of volunteers to re-volunteer should be taken into account by organizations that rely on them.

Background: In compliance with public health measures initiated by the Israel Ministry of Health following an outbreak of influenza, amantadine was administered to all patients in the psychogeriatric department of Lev Hasharon Mental Health Center to reduce transmission and illness severity in this susceptible population.

Objectives: To evaluate the potential beneficial effects of amantadine on elderly hospitalized patients with persistent schizophrenia.

Methods: We conducted a retrospective case review of the treatment effects of amantadine on the mental, cognitive and clinical states of elderly chronic schizophrenic patients who received concomitant amantadine treatment and were routinely evaluated with the Positive and Negative Syndrome Scale, the Mini Mental State Examination, and Sandoz Clinical Assessment Geriatric Scale.

Results: No significant differences before and after amantadine treatment were noted. Conclusion: Amantadine did not influence the mental, cognitive and clinical states of elderly schizophrenia patients and thus can be considered as an anti-influenza preventive measure for this population, when indicated.

survey. A tailor-made CME program may have contributed to the improvement in skills and quality of care.

Background: Enteral nutrition in the critically ill patient is often complicated by gastrointestinal intolerance, manifested by a large gastric residual volume. The frequency of GRV[1] assessment and the intolerant level above which feeding is stopped is controversial.

Objectives: To evaluate a novel approach to EN[2] by allowing high GRV and once-daily assessment that was correlated with the paracetamol absorption test.

Methods: We conducted a pilot prospective study in an 18 bed general intensive care unit. The study group comprised 52 consecutive critically ill mechanically ventilated patients. Enteral nutrition was started at full delivery rate. Once-daily assessment of GRV with three consecutively repeated threshold volumes of 500 ml was performed before stopping EN. The paracetamol absorption test was performed and correlated to GRV. Patients were divided into two groups: low GRV (< 500 ml), and high GRV (at least one measurement of GRV > 500 ml). Clinical outcome included maximal calories delivered, incidence of pneumonia, ICU[3] length of stay, and ICU and hospital mortality.

Results: There were 4 patients (9.5%) with ventilator-associated pneumonia in the low GRV group and 3 (30%) in the high GRV group (P = 0.12). GRV was inversely correlated to paracetamol absorption; however, neither GRV nor paracetamol absorption was associated with the development of pneumonia. Both groups had similar ICU length of stay (11.0 ± 8.2 vs. 13.8 ± 14.4 days, P = 0.41), and similar ICU (21% vs. 40%, P = 0.24) and hospital mortality (35% vs. 40%, P = 1.0).

Conclusions: In critically ill mechanically ventilated patients, allowing larger gastric residual volumes, measured once daily, enables enteral feeding with fewer interruptions which results in high calorie intake without significant complications or side effects.

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: Poisonings are a significant cause of pediatric morbidity and mortality. The Israel Poison Information Center provides clinical consultations on poisonings and drug information 24 hours a day.

Objective: To evaluate epidemiologic characteristics of pediatric poison exposures in Israel.

Methods: We reviewed computerized queries and performed a descriptive analysis of the Poison Center database pertaining to patients less than 18 years old during 2007.

Results: A total of 15,005 pediatric poison exposures were recorded, 80.3% of them occurring in children under 6 years old. Of the calls to the Poison Center, 78.6% were made by the public, 20.7% by physicians, and in 74.4% the call was within 2 hours of exposure. Most exposures occurred at home (89.3%) and were unintentional (89.5%). Among adolescents, most exposures were intentional (49.3%, 38.2% suicides), the time lapse until consultation was longer (37% > 2 hours), and more physicians (54.8%) consulted the Poison Center. Most cases were asymptomatic or mildly affected (92.3%), 54.4% in adolescents. The commonest substances involved in single poison exposure were detergents, antimicrobials, topical preparations, acetaminophen and scale removers; in adolescents the most common substances were acetaminophen, methylphenidate, non-steroidal anti-inflammatory drugs, atropine and ethanol. Moderate to severe toxicity was commonly associated with organophosphates, alkali, ethanol, Vipera palaestinae and neuroleptics. Most patients could be observed at home (66.6%), while more adolescents were referred to emergency departments (42.2% vs. 9.9%) or hospitalized (14.5% vs. 1.9%).

Conclusions: Pediatric poisonings are a significant health problem. The magnitude of the problem is greater in the young age group but more severe in adolescence, probably due to deliberate self-poisoning. Greater national efforts should be directed towards improved poison prevention, rational management of pediatric poisoning, and creating a national poisoning registry.
 

Background: One of the ominous complications following proximal gastrectomy or total gastrectomy is a leak from the esophagogastric or esophagojejunal anastomosis. An upper gastrointestinal swallow study is traditionally performed to confirm the anastomotic patency and lack of any leak before oral feeding can be initiated.

Objectives: To challenge the routine use of UGISs[1] following proximal or total gastrectomy in order to check the integrity of the gastroesophageal or jejunoesophageal anastomosis.

Methods: The charts of 99 patients who underwent PG[2] or TG[3]  for malignant pathology were retrospectively reviewed. UGISs were performed on day 6 following surgery using a water-soluble material.

Results: The UGISs were normal in 95 patients, with none displaying any complication related to the gastroesophageal or jejunoesophageal anastomosis. All four patients who experienced a leak from the anastomosis had an early stormy postoperative course.

Conclusions: Routine use of an UGIS to detect a leak following PG or TG is not justified. UGIS should be performed whenever signs of abdominal sepsis develop following this type or surgery.

Background: Trans-aortic pressure gradient in patients with aortic stenosis and left ventricular systolic dysfunction is typically low but occasionally high.

Objectives: To examine the distribution of trans-aortic PG[1] in patients with severe AS[2] and severe LV[3] dysfunction and compare the clinical and echocardiographic characteristics and outcome of patients with high versus low PG.

Methods: Using the echocardiographic laboratory database at our institution, 72 patients with severe AS (aortic valve area ≤ 1.0 cm²) and severe LV dysfunction (LV ejection fraction ≤ 30%) were identified. The characteristics and outcome of these patients were compared.

Results: PG was high (mean PG ≥ 35 mmHg) in 32 patients (44.4%) and low (< 35 mmHg) in 40 (55.6%). Aortic valve area was slightly smaller in patients with high PG (0.63 ± 0.15 vs. 0.75 ± 0.16 cm² in patients with low PG, P = 0.003), and LV ejection fraction was slightly higher in patients with high PG (26 ± 5 vs. 22 ± 5% in patients with low PG, P = 0.005). During a median follow-up period of 9 months 14 patients (19%) underwent aortic valve replacement and 46 patients (64%) died. Aortic valve replacement was associated with lower mortality (age and gender-adjusted hazard ratio 0.19, 95% confidence interval 0.05–0.82), whereas trans-aortic PG was not (P = 0.41).

Conclusions: A large proportion of patients with severe AS have relatively high trans-aortic PG despite severe LV dysfunction, a finding partially related to more severe AS and better LV function. Trans-aortic PG is not related to outcome in these patients.