Israel Medical Association Journal

Background: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. 

Objectives: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. 

Methods: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7–128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64–83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. 

Results: Five year progression-free survival was 68% (95%CI 59.8–74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3–0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). 

Conclusions: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.

 

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. 

Objectives: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.

Methods: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.

Results: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.

Conclusions: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT. 

 

Background: Medical history-taking is an essential component of medical care. 

Objectives: To assess and improve history taking, physical examination and management plan for hospitalized patients. 

Methods: The study consisted of two phases, pre- and post- intervention. During phase I, 10 histories were evaluated for each of 10 residents, a total of 100 histories. The assessment was done with a validated tool, evaluating history-taking (maximum 23 points), physical examination (23 points), assessment and plan (14 points) (total 60 points). Subsequently, half of these residents were informed that they were assessed; they received their scores and were advised regarding areas needing improvement. Phase II was identical to phase I. The primary endpoint was a statistically significant increase in score. 

Results: In the study group (receiving feedback after phase I) the physical examination improved from 9.3 ± 2.4 in phase I to 10.8 ± 2.2 in phase II (P < 0.001), while in the control group there was no change (11.3 ± 1.9 to 11.5 ± 1.8 respectively, P = 0.59). The assessment and plan component improved in the study group from 6.4 ± 2.7 in phase I to 7.4 ± 2.6 in phase II (P = 0.05), while no change was observed in the control group (8.2 ± 2.7 and 7.8 ± 2.3, P = 0.43). Overall performance improved in the study group from 30.4 ± 5.1 in phase I to 32.9 ± 4.5 in phase II (P = 0.01), a 10% improvement, while no change was observed in the control group (35.5 ± 6.0 to 34.6 ± 4.1, P = 0.4). 

Conclusions: A review of medical histories obtained by residents, assessed against a validated score and accompanied by structured feedback may lead to significant improvement. 

 

Background: Fertility treatments are responsible for the rise in high order pregnancies in recent decades and their associated complications. Reducing the number of embryos returned to the uterus will reduce the rate of high order pregnancies.     

Objectives: To explore whether obstetric history and parity have a role in the clinician’s decision making regarding the number of embryos transferred to the uterus during in vitro fertilization (IVF).

Methods: In a retrospective study for the period August 2005 to March 2012, data were collected from twin deliveries > 24 weeks, including parity, mode of conception (IVF vs. spontaneous), gestational age at delivery, preeclampsia, birth weight, admission to the neonatal intensive care unit (NICU), and Apgar scores. 

Results: A total of 1651 twin deliveries > 24 weeks were recorded, of which 959 (58%) were at term (> 37 weeks). The early preterm delivery (PTD) rate (< 32 weeks) was significantly lower with increased parity (12.6%, 8.5%, and 5.6%, in women with 0, 1, and ≥ 2 previous term deliveries, respectively). Risks for PTD (< 37 weeks), preeclampsia and NICU admission were significantly higher in primiparous women compared to those who had one or more previous term deliveries. Primiparity and preeclampsia, but not IVF, were significant risk factors for PTD. 

Conclusions: The risk for PTD in twin pregnancies is significantly lower in women who had a previous term delivery and decreases further after two or more previous term deliveries. This finding should be considered when deciding on the number of embryos to be transferred in IVF.  

 

Background: Syncope is a common clinical condition spanning from benign to life-threatening diseases. There is sparse information on the outcomes of syncopal patients who received an implantable cardiac defibrillator (ICD) for primary prevention of sudden cardiac death (SCD). 

Objectives: To assess the outcomes and prognosis of patients who underwent implantable cardiac defibrillator (ICD) implantation for primary prevention of SCD and compare them to patients who presented with or without prior syncope.

Methods: We compared the medical records of 75 patients who underwent ICD implantation for primary prevention of SCD and history of syncope to those of a similar group of 80 patients without prior syncope. We assessed the episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing (ATP) and mortality in each group during follow-up.

Results: Mean follow-up was 893 days (810–976, 95%CI) (no difference between groups). There was no significant difference in gender or age. Patients with prior syncope had a higher ejection fraction rate (35.5 ± 12.6 vs. 31.4 ± 8.76, P = 0.02), experienced more episodes of VT (21.3% vs. 3.8%, P = 0.001) and VF (8% vs. 0%, P = 0.01), and received more electric shocks (18.7% vs. 3.8%, P = 0.004) and ATP (17.3% vs. 6.2%, P = 0.031). There were no differences in inappropriate shocks (6.7% vs. 5%, P = 0.74), cardiovascular mortality (cumulative 5 year estimate 29.9% vs. 32.2%, P = 0.97) and any death (cumulative 5 year estimate 38.1% vs. 48.9%, P = 0.18).

Conclusions: Patients presenting with syncope before ICD implantation seemed to have more episodes of VT/VF and shock or ATP. No differences in mortality were observed

 

Background: The popularity of bicycle riding for recreation, exercise and transportation has grown enormously in recent years, which has led to an increased incidence of bicycle-related injuries. While these injuries involve mainly the musculoskeletal system, data on shoulder-specific injuries incurred while bike riding are lacking. Classifying these shoulder injuries may provide insight and assistance in the creation and implementation of effective protective gear and measures. 

Objectives: To investigate the types and mechanisms of shoulder injuries among cyclists.

Methods: This study retrospectively examined all cyclists who incurred shoulder injuries while riding and were admitted to the emergency department and shoulder clinic between January 2008 and November 2013. The study included 157 subjects with various bicycle-related shoulder injuries treated with either conservative or surgical measures. 

Results: Eighty-four percent of injuries were caused by a direct blow to the shoulder, 7% by falling on an outstretched hand, 6% were traction injuries, and 3% were due to hyper-abduction. Nine different clinical types of injury were observed; the most common injuries were clavicle fractures (32%), followed by acromioclavicular joint dislocations (22%), rotator cuff tears (22%), and humeral fractures (8%). Fifty-one percent of subjects were managed with conservative care and the remaining patients required surgical interventions. 

Conclusions: The shoulder injuries incurred while riding a bicycle span the entire spectrum of shoulder injuries and often result in debilitating conditions. Although the use of helmets is increasing, there is currently no effective protective gear or measures to prevent riders from suffering shoulder injuries. 

 

Background: The kinetics of high sensitivity cardiac troponin T (hs-cTnT) levels after elective, biphasic, direct-current cardioversion for persistent atrial fibrillation/flutter remains unknown.

Methods: We examined hs-cTnT kinetics in 24 patients at baseline and at 2, 6 and 24 hours post-cardioversion, and again at 7 and 30 days. We also examined levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, brain natriuretic peptide (BNP), and high sensitivity C-reactive protein (hs-CRP).

Results: Median (25th, 75th interquartiles) baseline hs-cTnT concentration was 19.8 (10.4, 35.2) ng/L with 14 patients presenting with levels above the 99th percentile (13 ng/L). Hs-cTnT levels did not change significantly over time although they tended to decrease by 30 days, 18.8 ng/L (12.5, 23.3). There was no significant rise in other markers of myocardial injury. Similarly, BNP and hs-CRP levels were elevated at baseline and tended to decrease over time.

Conclusions: Patients with persistent atrial fibrillation/flutter have elevated hs-cTnT levels, as part of a general rise in biomarkers such as BNP and hs-CRP, without a further rise after cardioversion. After cardioversion, there is a gradual non-significant decrease in biomarker levels over time, and thus a rise in hs-cTnT levels should not be attributed to cardioversion. 

 

Background: Cardiac resynchronization therapy (CRT) is a non-pharmacological option for patients with heart failure and interventricular dyssynchrony. Elevated red cell distribution width (RDW) reflects higher size and heterogeneity of erythrocytes and is associated with poor outcome in patients with chronic heart failure. 

Objectives: To examine the association between RDW levels and outcomes after CRT implantation.

Methods: We conducted a cohort analysis of 156 patients (126 men, median age 69.0 years) who underwent CRT implantation in our institution during 2004–2008. RDW was measured at three time points before and after implantation. Primary outcome was defined as all-cause mortality, and secondary outcome as hospital re-admissions. We investigated the association between RDW levels and primary outcome during a median follow-up of 61 months.

Results: Ninety-five patients (60.9%) died during follow-up. Higher baseline RDW levels were associated with all-cause mortality (unadjusted HR 1.35, 95%CI 1.20–1.52, P < 0.001). On multivariate analysis adjusted for clinical, electrocardiographic and laboratory variables, baseline RDW levels were associated with mortality (HR 1.33, 95%CI 1.16–1.53). RDW levels 6 months and 12 months post-implantation were also associated with mortality (HR 1.22, 95%CI 1.08–1.38, P = 0.001; and HR 1.15, 95%CI 1.01–1.32, P = 0.02, respectively). Patients who were re-admitted to hospital during follow-up (n=78) had higher baseline RDW levels as compared to those who were not (14.9%, IQR 14.0, 16.0% vs. 14.3%, IQR 13.7, 15.0%, respectively, P = 0.03). 

Conclusion: An elevated RDW level before and after CRT implantation is independently associated with all-cause mortality. 

 

Background: The surgical treatment of hip fractures remains controversial especially when considering age. 

Objectives: To investigate the long-term functional outcomes of displaced subcapital hip fractures that were reduced and surgically fixed using parallel cannulated screws in patients aged 60 years and younger. 

Methods: During the period 1996–2005, 27 patients under age 60 with displaced subcapital hip fractures classified as Garden III or IV were treated with fracture reduction and surgical internal fixation using cannulated screws. Patient outcomes were assessed using the Harris Hip Score (HHS) and physical examination.

Results: During a follow-up period of 8–17 years 4 of the 27 patients (14.8%) developed non-union/femoral head avascular necrosis and had undergone hip arthroplasty. All reoperations were performed within the first year after fracture fixation, all in the 50–60 year old age group. The revision rate among patients 50–60 years old was significantly higher than that of patients 50 years and younger (40% vs. 0%, P = 0.037). Mean HHS was higher for patients not requiring revision surgery (85.4) than for patients with revision surgery (75.5), but this difference was not significant.

Conclusions: Internal fixation using fracture reduction and cannulated screw fixation is a successful treatment modality for displaced subcapital hip fractures in patients younger than 50 years old. Patients aged 50–60 years may have a higher risk of avascular necrosis or non-union and require arthroplasty, often within the first year after fracture fixation. The long-term outcome following these fractures is good when excluding patients who had early complications.

 

Background: Atypical presentation of tuberculosis (TB) during pregnancy may cause diagnostic delay and adversely influence pregnancy outcome. 

Objectives: To examine the incidence and clinical and epidemiological features of TB during pregnancy and investigate infection control measures at delivery and during the postpartum period.

Methods: We retrospectively evaluated all reported cases of TB diagnosed during pregnancy to 6 months postpartum in Israel’s Northern Health District (2002–2012). 

Results: Active TB was detected in six patients; all were negative for human immunodeficiency virus (HIV). Two patients were diagnosed in the postpartum period, and four had pulmonary involvement. The average incidence during this period (3.9 per 100,000 pregnancies) was similar to that in the general population. Five patients were at high risk of contracting TB due to either recent immigration from a high-burden country or being in contact with another individual with active TB. Patients with pleuropulmonary involvement had prolonged cough and abnormal chest X-rays, without fever. Diagnosis was delayed for 3 to 7 months from symptom onset. Investigation of the newborn to rule out intrauterine infection was conducted in only one of four relevant cases. All patients were infected with organisms susceptible to all first-line drugs, and all were cured with standard therapy.

Conclusions: There was a considerable delay in the diagnosis of TB among pregnant women, and investigation of the newborn upon delivery to rule out TB infection was routinely omitted. Effective management of TB during pregnancy and the postpartum period requires a multidisciplinary approach including an obstetrician, pediatrician, TB specialist, and public health physician.