Israel Medical Association Journal

Background: More than 90% of all thyroid cancers are differentiated thyroid carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used risk stratification systems for DTC include: European Organization for Research and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor, Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion). Other systems are also utilized. Several new factors that may be involved in DTC risk stratification have emerged in recent studies, with other "traditional" factors being challenged. 

Objectives: To present recent updates in the literature on new potential prognostic factors for DTC.

Methods: We conducted a literature review and analysis of publications regarding DTC prognostic factors or risk stratification published in the last 10 years. 

Results: Several new factors with potential prognostic implications for DTC were noted, including family history, lymph node involvement parameters, positive PET-CT findings, multifocal disease, thyroglobulin level and several molecular markers including BRAF. Increasing age is associated with poorer outcome in DTC; however, recent studies suggest that the cutoff point of 45 years may be contested. Furthermore, several studies have shown contradictory results regarding male gender as a negative prognostic factor, thus questioning its prognostic significance. 

Conclusions: A number of new factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined.

 

Background: Syncope prognosis varies widely: 1 year mortality may range from 0% in the case of vasovagal events up to 30% in the presence of heart disease. 

Objectives: To assess the outcomes and prognosis of patients with implantable cardiac defibrillator (ICD) and indication of primary prevention and compare patients presenting with or without prior syncope.

Methods: We reviewed the charts of 75 patients who underwent ICD implantation with the indication of primary prevention and history of syncope and compared them to a control group of 80 patients without prior syncope. We assessed the number of ventricular tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing (ATP), and death in each group during the follow-up.

Results: Mean follow-up was 893 days (810–976, 95% confidence interval) (no difference between groups). Patients with prior syncope had a higher ejection fraction (EF) (35.5 ± 12.6 vs. 31.4 ± 8.76, P = 0.02), more episodes of VT (21.3% vs. 3.8%, P = 0.001) and VF (8% vs. 0%, P = 0.01) and also 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), in 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) during the follow-up.

Conclusions: Syncopal patients before ICD implantation seem to have more episodes of VT/VF and shock or ATP. No mortality differences were observed

 

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: Trauma is the leading cause of childhood morbidity and mortality. Abdominal bleeding is one of the common causes of mortality due to trauma. Angiography and embolization are well recognized as the primary treatments in certain cases of acute traumatic hemorrhage in adults; however, evidence is lacking in the pediatric population. 

Objectives: To assess the safety and efficacy of transcatheter arterial embolization (TAE) for blunt and penetrating abdominal and pelvic trauma in the pediatric age group.

Methods: Three children with blunt abdominal trauma and one child with iatrogenic renal injury (age 4–13 years) were managed with TAE for lacerated liver (one patient), pelvic fractures (one patient) and renal injuries (two patients). The first two patients, victims of road accidents, had multisystem injuries and were treated by emergency embolization after fluid resuscitation in the Emergency Department (ED). The other two patients had renal injuries: a 4 year old boy with blunt abdominal trauma was diagnosed on initial computed tomography with an unexpected Wilms tumor and was treated with embolization 1 day after admission due to hemodynamic deterioration caused by active arterial tumor bleeding. The following day he underwent successful nephrectomy. The other patient was 13 year old boy with nephrotic syndrome who underwent renal biopsy and developed hemodynamic instability. After fluid resuscitation, he underwent an initial negative angiography, but second-look angiography the following day revealed active bleeding from an aberrant renal artery, which was then successfully embolized.

Results: In all four patients, TAE was diagnostic as well as therapeutic, and no child required surgical intervention for control of bleeding.

Conclusions: We propose that emergency transcatheter angiography and arterial embolization be considered following resuscitation in the ED as initial treatment in children with ongoing bleeding after blunt abdominal trauma or iatrogenic renal injury. Implementation of this policy demands availability and cooperation of the interventional radiology services. 

 

Background: Although 5-amino-salycilic acids (5-ASA) are often used with corticosteroid treatment in moderate-to-severe ulcerative colitis, the value of continuing/initiating 5-ASA in this clinical setting has not been explored. 

Objectives: To investigate the impact of a combination 5-ASA+corticosteroid therapy on the outcome of hospitalized patients with acute moderate-severe ulcerative colitis. 

Methods: We conducted a retrospective study of patients hospitalized with moderate-severe ulcerative colitis in two centers, Israel and South Korea. Patients were classified into those who received 5-ASA and corticosteroids and those who received corticosteroids alone. Analysis was performed for each hospitalization event. The primary outcome was the rate of treatment failure defined as the need for salvage therapy (cyclosporin-A/infliximab/colectomy). The secondary outcomes were 30 days re-admission rates, in-hospital mortality rates, time to improvement, and length of hospitalization. 

Results: We analyzed 209 hospitalization events: 151 patients (72%) received 5-ASA+corticosteroids and 58 (28%) corticosteroids alone. On univariate analysis the combination therapy group had a lower risk for treatment failure (11% vs. 31%, odds ratio 0.28, 95% confidence interval 0.13–0.59, P = 0.001). However, this difference disappeared on multivariate analysis, which showed pre-admission oral corticosteroid treatment to be the most significant factor associated with the need for salvage therapy. 

Conclusions: A signal for possible benefit of a combination 5-ASA and corticosteroids therapy was found, but was confounded by the impact of pre-admission corticosteroid treatment. 

 

Background: Patients with type 1 diabetes (T1D) are exempt from conscript military service, but some volunteer for national service. 

Objectives: To evaluate the effect of national service (military or civil) on metabolic control and incidence of acute diabetes complications in young adults with T1D. 

Methods: Clinical and laboratory data of 145 T1D patients were retrieved from medical records. The cohort comprised 76 patients volunteering for national service and 69 non-volunteers. Outcome measures were HbA1c, body mass index-standard deviation scores (BMI-SDS), insulin dosage, and occurrence of severe hypoglycemia or diabetic ketoacidosis (DKA). 

Results: Metabolic control was similar in volunteers and non-volunteers: mean HbA1c at various time points was: 7.83 ± 1.52% vs. 8.07% ± 1.63 one year before enlistment age, 7.89 ± 1.36% vs. 7.93 ± 1.42% at enlistment age, 7.81 ± 1.28% vs. 8.00 ± 1.22% one year thereafter, 7.68 ± 0.88% vs. 7.82 ± 1.33% two years thereafter, and 7.62 ± 0.80% vs. 7.79 ± 1.19% three years thereafter. There were no significant changes in HbA1c from baseline throughout follow-up. BMI and insulin requirements were similar and remained unchanged in volunteers and controls: mean BMI-SDS one year before enlistment age was 0.23 ± 0.83 vs. 0.29 ± 0.95, at enlistment age 0.19 ± 0.87 vs. 0.25 ± 0.98, one year thereafter 0.25 ± 0.82 vs. 0.20 ± 0.96, two years thereafter 0.10 ± 0.86 vs. 0.15 ± 0.94, and three years thereafter 0.20 ± 0.87 vs. 0.16 ± 0.96. Mean insulin dose in U/kg/day one year before enlistment age was 0.90 ± 0.23 vs. 0.90 ± 0.37, at enlistment age 0.90 ± 0.28 vs. 0.93 ± 0.33, one year thereafter 0.86 ± 0.24 vs. 0.95 ± 0.33, two years thereafter 0.86 ± 0.21 vs. 0.86 ± 0.29, and three years thereafter 0.87 ± 0.23 vs. 0.86 ± 0.28. There were no episodes of severe hypoglycemia or DKA in either group. 

Conclusions: Our data indicate that during voluntary national service young adults with T1D maintain metabolic control similar to that of non-volunteers. 

 

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: Prophylaxis for hospitalized venous-thromboembolic events (VTEs) is frequently underutilized, in part due to lack of a simple risk assessment model (RAM). 

Objectives: To compare patient selection and administration of VTE prophylaxis according to the American College of Chest Physicians (ACCP) 2008 guidelines versus the newer 2012 guidelines, and assess the feasibility of developing simpler local RAMs.

Methods: We conducted a prospective assessment of VTE risk among 300 unselected consecutive patients admitted to a medical hospital ward, using the 2008 and 2012 ACCP guidelines. The frequency and relative weight of each risk factor in the 2012 ACCP guidelines were used to develop a local VTE RAM.

Results: VTE prophylaxis was indicated by the 2008 and 2012 ACCP guidelines in 40% and 42% of the cohort respectively, and was administered in 28% and 26% of eligible patients, respectively. Contraindication to VTE prophylaxis was found in 29% of patients according to both guidelines. In comparison to the 2008 guidelines, sensitivity and specificity of the 2012 guidelines were 96% and 88%, respectively. A local RAM based on the following concise score, comprising age, malignancy and immobility, correctly identified 99% of at-risk patients based on the 2012 guidelines, with a sensitivity and specificity of 98% and 95%, respectively.

Conclusions: Both guidelines performed to a similar degree and were poorly implemented in daily practice. A simplified RAM accurately identified the vast majority of these eligible patients. The development of local RAMs is feasible and may result in higher utilization rates.

 

Background: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis. 

Objectives: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process.

Methods: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009–2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression.

Results: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P < 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95%CI 1.3–12.4%, P = 0.014). 

Conclusions: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups. 

 

Background: Radial artery occlusion (RAO) may occur following transradial catheterization, precluding future use of the vessel for vascular access or as a coronary bypass graft. Recanalization of RAO may occur; however, long-term radial artery patency when revascularization is more likely to be required has not been investigated. Transradial catheterization is usually performed via 5-Fr or 6-Fr catheters. Insertion of 7-Fr sheaths into the radial artery enables complex coronary interventions but may increase the risk of RAO. 

Objective: To assess the long-term radial artery patency following transradial catheterization via 7-Fr sheaths.

Methods: Antegrade radial artery blood flow was assessed by duplex-ultrasound in 43 patients who had undergone transradial catheterization via a 7-Fr sheath. 

Results: All patients had received intravenous unfractionated heparin with a mean activated clotting time (ACT) of 247 ± 56 seconds. Twenty-four patients (56%) had received a glycoprotein IIbIIIa inhibitor and no vascular site complications had occurred. Mean time interval from catheterization to duplex-ultrasound was 507 ± 317 days. Asymptomatic RAO was documented in 8 subjects (19%). Reduced body weight was the only significant univariate predictor of RAO (78 ± 11 vs. 89 ± 13 kg, P = 0.031). In a bivariate model using receiver operator characteristic (ROC) curves, the combination of lower weight and shorter ACT offered best prediction of RAO (area under the ROC curve 0.813). 

Conclusions: Asymptomatic RAO was found at late follow-up in approximately 1 of 5 patients undergoing transradial catheterization via a 7-Fr sheath and was associated with lower body weight and shorter ACT. 

 

Background: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect on outcome of age at initial exposure have yet to be determined. 

Objectives: To identify the characteristics of radiation-induced thyroid carcinoma.

Methods: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. 

Results: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS).

Conclusions: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

 

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

Background: Diabetes mellitus (DM) is a metabolic sequel in people infected with HIV, especially following the advent of HAART. This may be a particular concern in immigrants due to lifestyle changes. 

Objectives: To characterize the prevalence of DM in HIV-infected Ethiopians in Israel, and to define the risk factors.

Methods: We retrospectively screened the records of 173 HIV-infected Ethiopians and 69 HIV-infected non-Ethiopian HIV patients currently registered at the HIV Clinic of Meir Medical Center. Data were also retrieved from 1323 non-HIV Ethiopians treated in the hospital between 2007 and 2012. The presence of DM was determined by family physician diagnosis as recorded in the hospital database or by the presence of one or more of the following: fasting glucose > 127 mg/dl, hA1C > 6.5% (> 48 mmol/mol), or blood glucose > 200 mg/dl. Population data and risk factors for DM were analyzed by univariate and multivariate analyses. 

Results: Among HIV-infected Ethiopian subjects, the prevalence of DM was 31% (54/173) compared to 4% (3/69) in HIV-infected non-Ethiopians and 8% (102/1323) in non-HIV-infected Ethiopians (P < 0.0001). The relatively increased prevalence of DM was age independent, but most noticeable in those under the median age (< 42 years). Body mass index (BMI) was a predictor for DM (OR 1.263, CI 1.104–1.444, P = 0.001), although its values did not vary between the two ethnic groups. 

Conclusions: HIV-infected Ethiopians are more likely to develop DM at low BMI values compared to non-Ethiopians. This observation questions the relevance of accepted BMI values in this population and suggests that preventive measures against DM be routinely taken in these subjects.