Israel Medical Association Journal

Background: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008 for the treatment of metastatic renal cell carcinoma (mRCC), based on an international trial. However, the efficacy of sunitinib treatment in Israeli mRCC patients has not been previously reported.

Objectives: To report the outcome and associated factors of sunitinib treatment in a large cohort of Israeli mRCC patients.

Methods: We conducted a retrospective study of an unselected cohort of mRCC patients who were treated with sunitinib during the period 2006–2013 in six Israeli hospitals. Univariate and multivariate analyses were performed to determine the association between treatment outcome and clinicopathologic factors.

Results: We identified 145 patients; the median age was 65 years, 63% were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy-nine percent (n=115) had clinical benefit (complete response 5%, n=7; partial response 33%, n= 48; stable disease 41%, n=60); 21% (n=30) were refractory to treatment. Median progression-free survival (PFS) was 12 months and median overall survival 21 months. Factors associated with clinical benefit were sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated with PFS were female gender [hazard ratio (HR) 2, P = 0.004], pre-sunitinib treatment neutrophil to lymphocyte ratio ≤ 3 (HR 2.19, P = 0.002), and active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR 0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment interrupted in 39% (n=57). 

Conclusions: The efficacy of sunitinib treatment for mRCC among Israeli patients is similar to that of international data.

Objectives: To investigate the association between CAD and H. pylori infection using MPI.

Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD-positive group included patients with ischemia and/or myocardial infarctions (MI) on a stress MPI, coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients’ demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.

Results: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD- positive (odds ratio 1.83, 95% confidence interval 1.06–3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44–7.84, P = 0.005). No association was noted with CagA positivity.

Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors. 

Objectives: To compare the outcomes of AKA and BKA and to identify risk factors for poor outcome following leg amputation.

Methods: This retrospective cohort study comprised 188 consecutive patients (mean age 72 years, range 25–103, 71% males) who underwent 198 amputations (91 AKA, 107 BKA, 10 bilateral procedures) between February 2007 and May 2010. Included were male and female adults who underwent amputations for ischemic, infected or gangrenotic foot. Excluded were patients whose surgery was performed for other indications (trauma, tumors). Mortality and reoperations (wound debridement or need for conversion to a higher level of amputation) were evaluated as outcomes. Patient- and surgery-related risk factors were studied in relation to these primary outcomes.

Results: The risk factors for mortality were dementia [hazard ratio (HR) 2.769], non-ambulatory status preoperatively (HR 2.281), heart failure (HR 2.013) and renal failure (HR 1.87). Resistant bacterial infection (HR 3.083) emerged as a risk factor for reoperation. Neither AKA nor BKA was found to be an independent predictor of mortality or reoperation.

Conclusions: Both AKA and BKA are associated with very high mortality rates. Mortality is most probably related to serious comorbidities (renal and heart disease) and to reduced functional status and dementia. Resistant bacterial infections are associated with high rates of reoperation. The risk factors identified can aid surgeons and patients to better anticipate and possibly prevent severe complications.

Objective: To assess the impact of multiple births on the severity of RSV infection and define risk factors for acquiring RSV infection in infants of multiple birth.

Methods: Clinical data on infants hospitalized with RSV infection between 2008 and 2010 were retrospectively collected.

Results: Twins comprised 7.6% (66/875) of hospitalized infants with RSV bronchiolitis during the study period. Infants in the twin group were younger (122.4 ± 131.7 vs. 204.5 ± 278.8 days, P = 0.014), had a lower mean gestational age (35.3 ± 2.6 vs. 38.6 ± 2.5 weeks, P < 0.001), and were more likely to have been born prematurely compared with singleton infants (65.6% vs. 13%, P < 0.001). On a multivariable logistic regression analysis, young age, early gestational age and male gender were the only variables identified as risk factors for pediatric intensive care unit admission (P < 0.001, P < 0.001 and P = 0.03, respectively). In contrast, the mere fact of a child being a twin was not found to be a significant risk factor for disease severity. In addition, if one twin is hospitalized due to RSV infection, the other has a 34% chance of also being hospitalized with bronchiolitis. Young age was a significant risk factor for hospitalization of the second twin (P < 0.001).

Conclusions: Our findings suggest that twins hospitalized with RSV bronchiolitis do not have an increased risk for severe infection as compared to singletons. However, a twin of an infant hospitalized with RSV infection has a considerable risk of also being hospitalized with bronchiolitis, thus close monitoring is recommended. 

Objectives: To characterize the clinical features and outcomes of body packers hospitalized at the Sheba Medical Center.

Methods: We conducted a retrospective case series of body packers hospitalized between January 2010 and October 2012 in our medical center. Electronic medical records and imaging files were reviewed to extract clinical, laboratory and radiological data as well as details on medical treatments.

Results: We identified 23 body packers (mean age 38 ± 10 years), 20 of whom smuggled cocaine from South America. The number of packets transported ranged from 1 to 242 (median 42) and duration of hospitalization from 1 to 14 days (median 2). Two subjects required surgical intervention. All others were treated conservatively by polyethylene glycol-electrolyte lavage solution, laxatives, or watchful waiting. Ten patients underwent a urinary screen for illicit drugs, 7 of whom tested positive for cocaine and 2 for cannabinoids. Abdominal X-rays were performed in all patients at admission, and 14 had follow-up imaging, including abdominal CT scans without contrast media in 8.

Conclusions: The main treatment goals for body packers are the rapid excretion of drug packets and early detection of complications, i.e., drug intoxication and bowel obstruction. We suggest the use of a structured treatment approach for the in-hospital management of body packers.

Objectives: To evaluate glycemic control, prevalence of diabetic ketoacidosis (DKA) at presentation, diabetic complications rate, and associated autoimmune diseases in a pediatric T1DM patient population in the Negev area.

Methods: Clinical and demographic details of 168 T1DM patients were evaluated, including HbA1C levels, long-term complications, related autoimmune diseases, and insulin pump usage. The data were analyzed and the Jewish and Bedouin patient groups compared.

Results: Only 13.1% of the patients had reached the HbA1C levels recommended by the current guidelines at the first and second year follow-up visits, and 9.5% and 7.1% at the third and fourth year visits, respectively. A significant difference in HbA1c levels between Jewish and Bedouin patients was found (P = 0.045 at the first year follow-up, P ≤ 0.01 thereafter). Significant difference was found between the Jewish and the Bedouin groups regarding presentation with DKA, 33% and 56% of the patients respectively (P = 0.01).

Conclusions: Existent glycemic control in daily practice is far from the guideline goals. Bedouin ethnicity was associated with less favorable diabetes control, emphasizing the need for better awareness of T1DM and its treatment options in this population. More resources should be directed to address T1DM in the general population, especially among the Bedouin.

Objectives: To review our experience with laparoscopic repair of GDH, emphasizing preoperative investigation, technical aspects, and outcome.

Methods: We conducted a retrospective review of patients operated on for GDH who were diagnosed when at least half the stomach was found in the mediastinum at surgery. Technical aspects and surgical outcomes were evaluated.

Results: Fifty patients underwent laparoscopic GDH repair during an 8 year period. Four patients admitted with acute symptomatic volvulus of the stomach were initially treated by endoscopic decompression followed by surgery during the same admission. Two cases were converted to open surgery. Initial surgery was successful in 45 patients; 3 had an immediate recurrence, 1 was reoperated for dysphagia during the same admission, and 1 had a mediastinal abscess. During long-term follow-up, six patients required reoperation for recurrent hernias. Another four patients had asymptomatic partial herniation of the stomach. The main reason for failure was incomplete reduction of the hernia sac, especially the posterior component. No correlation was found between the type of repair and surgical failure. Most patients who did not undergo an anti-reflux procedure had postoperative reflux unrelated to their preoperative workup.

Conclusions: Laparoscopic repair of GDH is challenging, but practical and safe. It should be the treatment of choice for this potentially life-threatening condition. Careful attention to pitfalls, such as the posterior element of the sac, and routine performance of an anti-reflux procedure are crucial.

Objectives: To evaluate the feasibility of induction chemotherapy with docetaxel-cisplatin-5-flurouracil (TPF) followed by external beam radiotherapy (EBRT) with concomitant chemotherapy (CRT) or cetuximab (ERT) in the treatment of patients with advanced SCCHN.

Methods: We reviewed the data of all patients with advanced SCCHN, stage III and IV, treated in 2007–2010. Tolerability was assessed and scored according to the proportion of patients completing the planned study protocol. Toxicity was scored using the U.S. National Cancer Institute Common Toxicity Criteria (version 4) for classification of adverse events.

Results: The study included 53 patients. TPF was initiated at a reduced dose in 13 patients (25%). Twenty-two patients (41.5%) received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) and 42 (77%) completed treatment according to schedule. During the induction phase one patient (2%) died and 24 (45%) had one or more grade 3-4 complications. The number of patients who developed neutropenia was lower in the group that received primary GCSF prophylaxis. Secondary dose reductions were required in 21% of the patients.

Conclusions: Induction TPF was associated with grade 3-4 toxicity. Prophylaxis with GCSF should be part of the treatment regimen.

Objectives: To determine if and to what degree the evacuation of Gush Katif caused a worsening in the health status of the evacuees.

Methods: In this retrospective cohort study we assessed the medical records of 2962 evacuees for changes in prevalence of diabetes, hypertension and ischemic heart disease in the period beginning 1 year before and ending 5 years after the evacuation. The findings were compared to those for the general Israeli population. A questionnaire was distributed to 64 individuals to assess lifestyle and social change.

Results: An increase in diabetes and hypertension was found in men aged 45–64. The prevalence of diabetes mellitus in the 45–54 male group rose from 8.7% in 2004 to 12.6% in 2007 to 18.7% in 2010; in the 55–64 age group it rose from 24.6% in 2004 to 29.9% in 2007 to 32.9% in 2010. Hypertension in 45–64 year old men rose from 27.1% in 2004 to 35.12% in 2010. The increases in diabetes were significant and higher than those in the general population. The increases in hypertension were of similar magnitude. The prevalence of heart disease did not change and is similar to that in the general population. The questionnaire sample showed an increase in depression and overweight.

Conclusions: The Gush Katif evacuation appears to be associated with increased morbidity of chronic disease. This may be attributed to any of several mechanisms, with unemployment, depression, inactivity and overweight playing significant roles. Preventive medical interventions and measures should be employed to screen and treat this population which underwent a major stressful event and as a result seem at greater risk than their peers.

Objectives: To describe and identify clinical characteristics, prognostic factors and visual outcome in a group of patients with OGI in southern Israel.

Methods: We conducted a retrospective review of all cases of OGI examined in the ophthalmology department at Soroka University Medical Center, Beer Sheva, Israel, from 1996 to 2005. A total of 118 eyes with OGI were detected and analyzed statistically. We recorded demographic data, cause of injury, initial visual acuity (VA), associated globe morbidity and injuries, Ocular Trauma Score (OTS), surgical procedures, postoperative complications, and final VA.

Results: The mean age of the study group was 36.1 years and included 84% males. The median follow-up was 13.3 months (range 6–66 months). The annual incidence of open globe injuries was 3.1 cases/100,000. In 84 cases (71%) the mechanism of open eye injury was laceration. Most of the injuries were work related (45%). Bilateral injury was observed in two patients. An intraocular foreign body was observed in 45 eyes (38%). Primary surgical repair was performed in 114 eyes. Six patients (5.1%) had complications with post-traumatic endophthalmitis and 12 patients (10.1%) underwent evisceration or enucleation. Clinical signs associated with poor visual outcomes included reduced initial VA, eyelid injury, and retinal detachment at presentation.

Conclusions: In our study population the most important prognostic factors in open globe injury were initial VA, eyelid injury and retinal detachment.

Objectives: To report our first year experience with a CPU located in an internal medicine department as compared to the year before establishment of the CPU.

Methods: We retrospectively evaluated the medical records of consecutive patients who were admitted to our internal medicine department for the investigation of chest pain for 2 different years: a year before and a year after the establishment of the CPU in the department. We focused on the patients' characteristics and the impact of the CPU regarding the investigational modalities used and the length of in-hospital stay.

Results: In the year before establishment of the CPU, 258 patients were admitted to our department with chest pain, compared to 417 patients admitted to the CPU in the first year of its operation. All patients were followed for serial electrocardiographic and cardiac enzyme testing. All CPU patients (100%) underwent investigation compared to only 171 patients (66%) in the pre-CPU year. During the year pre-CPU, 164 non-invasive tests were performed (0.64 tests per patient) compared to 506 tests (1.2 tests/patient) in the CPU population. Coronary arteriography was performed in 35 patients (14%) during the pre-CPU year, mostly as the first test performed, compared to 61 patients (15%) during the CPU year, mostly as a second test, with only 5 procedures (1.1%) being the first test performed. The length of hospitalization was significantly shorter during the CPU year, 37.8 ± 29.4 hours compared to 66.8 ± 46 hours in the pre-CPU year.

Conclusions: Establishment of a CPU in an internal medicine department significantly decreased the need for invasive coronary arteriography as the first modality for investigating patients admitted with chest pain, significantly decreased the need for invasive procedures (especially where no intervention was performed), and significantly shortened the hospitalization period. CPU is an effective facility for rapid and effective investigation of patients admitted with chest pain.