Israel Medical Association Journal

Background: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease.

Objectives: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA).

Methods: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization.

Results: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06–6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01–1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01–1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22–4.11).

Conclusions: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

Background: Access-site bleeding is a common complication of transfemoral transcatheter aortic valve implantation (TAVI). Percutaneous stent-graft implantation within the femoral artery may achieve hemostasis and avert the need for more invasive surgical vascular repair; however, failure to advance a guidewire antegradely via the injured vessel may preclude stent delivery. While retrograde stent-graft delivery from the distal vasculature may potentially enable percutaneous control of bleeding, this approach has not been reported.

Objectives: To assess the feasibility of a retrograde approach for stent-graft implantation in the treatment of access-site bleeding following transfemoral TAVI.

Methods: A prospective TAVI registry was analyzed. Of 349 patients who underwent TAVI, transfemoral access was used in 332 (95%). Access-site injury requiring stent-graft implantation occurred in 56 (17%). In four patients (7%), antegrade wiring across the site of vascular injury was not possible and a retrograde approach for stent delivery was used.

Results: Distal vascular access was achieved via the superficial femoral or profunda artery. Retrograde advancement of a polymer-coated 0.035” wire to the abdominal aorta, followed by stent-graft delivery to the common femoral artery, achieved hemostasis in all cases. During a median (interquartile range) follow-up period of 198 (618) days (range 46–2455) there were no deaths and no patient required additional vascular interventions.

Conclusions: A retrograde approach for stent-graft delivery is feasible and allows percutaneous treatment of a common femoral artery injury following TAVI in patients who are not suitable for the conventional antegrade approach.

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

Aging has been associated with perceived lowering of health, especially in post-traumatic individuals. The effects may be more complex or even different for Holocaust survivors as they age due to their inherited resilience and life perspective. A cross-sectional study was conducted of Holocaust survivors and a matched comparison group recruited from the general Israeli population. All participants underwent a personal interview and completed the Cumulative Illness Rating Scale and a survey of subjective Likert-scale questions about perceived health. The study comprised 214 older adults: 107 Holocaust survivors and 107 comparison participants; 101 women and 113 men. The mean age for the participants was 80.7 ± 4.7 years (range 68–93). Holocaust survivors did not differ from comparison subjects in general health measures (mean 51.50 ± 3.06 vs. 52.27 ± 3.24, respectively). However, the Holocaust survivors' subjective health was significantly lower, F (2,211) = 4.18, P < 0.05, and associated with decreased quality of life. The present study demonstrates the complex interplay between general and subjective health and suggests that future interventions need to focus on improving the psychological and social well-being of Holocaust survivors to achieve successful aging.

Background: Neuroblastoma is the most common non-central nervous system (CNS) solid malignant tumor in children. The surgical treatment of high-risk neuroblastoma presents a challenge, and the benefits of aggressive surgical resection have been called into question.

Objectives: To examine our experience with surgical resection of neuroblastoma.

Methods: We report on a retrospective chart review of our preliminary surgical experience in 25 patients with neuroblastoma who underwent surgery performed by a single surgeon at two institutions over a 3 year period. Demographic data, including stage of tumor and risk stratification, were recorded. Primary outcome was total gross resection. Patients were followed for 3 years after surgery.

Results: We found that 80% of the patients, including those with high-risk neuroblastoma tumors, had total gross resection of their tumor with minimal operative morbidity and no mortality; 88% had greater than 90% resection of their tumor. Overall, 3 year survival was 84% (21/25).

Conclusions: Resection of neuroblastoma, even large, high-risk, bilateral tumors, was possible when performed by surgical teams with considerable experience.

Background: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. 

Objectives: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. 

Methods: In March 2013 the authors launched a seven-component intervention program: 

1. Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory


2. Education program for the emergency department staff


3. Dissemination of information regarding the urgency of the PPCI decision


4. Activation of the catheterization team by a single phone call


5. Reimbursement for transportation costs to on-call staff who use their own cars


6. Improvement in the quality of medical records


7. Investigation of failed cases and feedback 

Results: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. 

Conclusions: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival. 

 

Background: Biallelic BLM gene mutation carriers are at an increased risk for cancer, including colorectal cancer (CRC). Whether heterozygous BLM gene mutations confer an increased cancer risk remains controversial.

Objectives: To evaluate CRC and endometrial cancer risk in BLM heterozygous mutation carriers.

Methods: Jewish Ashkenazim at high risk for colon or endometrial cancer and endometrial cancer cases unselected for family history were genotyped for the BLM^Ash predominant mutation.

Results: Overall, 243 high-risk individuals were included: 97 men CRC patients (55.12 ± 12.3 years at diagnosis), 109 women with CRC (56.5 ± 13.7 years), 32 women with endometrial cancer (58.25 ± 13.4 years) and 5 women with both CRC and endometrial cancer. In addition, 120 unselected Ashkenazi women with endometrial cancer (64.2 ± 11.58 years) were genotyped. The BLM^Ash mutation was present in 4/243 (1.65%) high-risk patients; 2 CRC (0.97%) 2 endometrial cancer (5.4%), and 1/120 unselected endometrial cancer patients (0.84%). Notably, in high-risk cases, BLM^Ash mutation carriers were diagnosed at a younger age (for CRC 47.5 ± 7.8 years; P = 0.32 ; endometrial cancer 49.5 ± 7.7 years; P = 0.36) compared with non-carriers.

Conclusions: Ashkenazi high risk CRC/endometrial cancer, and women with endometrial cancer have a higher rate of BLM^Ash heterozygous mutation compared with the general population. BLM^Ash heterozygous mutation carriers are diagnosed with CRC and endometrial cancer at a younger age compared with non-carriers. These observations should be validated and the possible clinical implications assessed.

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Background: The treatment of patients hospitalized with heart failure (HHF) and ambulatory chronic heart failure (CHF) differs in various countries.

Objective: To evaluate the management and outcomes of patients with HFF and CHF in Israel compared to those in other European countries who were included in the ESC-HF Long-Term Registry.

Methods: From May 2011 to April 2013, heart failure patients – 467 Israelis and 11,973 from other countries – were evaluated. The Israeli patients included 178 with HHF and 289 with CHF. One year outcomes, including all-cause and cardiovascular mortality as well as HHF, were evaluated.

Results: The HHF Israeli patients were older than their CHF Israeli counterparts, had more co-morbidities, included more women, and were treated less frequently with medications suggested by European guidelines. The Israeli HHF patients had similar all-cause 1 year mortality rates compared to HHF patients from other participating countries, but their cardiovascular (CV) mortality was lower, while a significantly higher rate of all-cause and HHF was noted. The Israeli CHF patients were older, suffered from more co-morbidities and had prior cardio-electronic implantable devices. In addition, they had higher mortality rates, especially non-CV, and were more frequently hospitalized, compared to CHF patients from other countries.

Conclusions: The Israeli patients with heart failure differed in their baseline characteristics and the therapeutic approach. Despite high usage of treatments recommended by official guidelines, especially among CHF patients, mortality, particularly in HHF patients, remained high.

Background: Deliberate self-harm (DSH) increases the danger of future suicide death and the risk increases with age. Self-harm in older adults is often associated with greater suicidal intent and lethality. 

Objectives: To investigate clinical and psychosocial variables of older patients (age ≥ 65 years) assessed due to DSH, compared with younger adults.

Methods: Patients admitted to the Emergency Department following DSH during an 8 year period were included.

Results: Of 1149 participants, 187 (16.6%) were older adults (age ≥ 65) and 962 (83.4%) were younger adults (< 65). The older adults reported DSH closer to mid-day (P < 0.01) and suffered more frequently from adjustment disorder and depression. Personality disorders and schizophrenia were less commonly diagnosed (P < 0.001). Prescription medication (sedatives and hypnotics) were a more frequent means (88% vs. 71%) of DSH among older patients. Younger patients with DSH used over-the-counter medications (21.9% vs. 6.4%) three times more than did the older patients (P < 0.01). Past DSH was significantly more frequent in younger adults. Following DSH the older patients were frequently admitted for further general hospitalization (P < 0.001). 

Conclusions: Older adults with DSH are a unique group with different clinical characteristics. There is a need for targeted prevention strategies and education of caregivers regarding DSH in older adults.

 

Background: Physical restraints are a common, albeit controversial, tool used in the acute care setting. 

Objectives: To determine the prevalence of physical restraint use in an acute care hospital. Secondary objectives were to determine whether physical restraints are used more commonly in night shifts, identify patient risk factors for physical restraint use, and establish if staff-to-patient ratio correlated with physical restraint use.

Methods: An observational cross-sectional study was conducted over 3 months in 2013 in the medical, surgical and intensive care units in a mid-sized general hospital. All the physically restrained patients in each observation were added to the registry. At each observation one department was selected for comparison and all non-restrained patients were added to the registry.

Results: The study population comprised 2163 patients. Seventy-six were restrained and 205 were included as case-controls. The prevalence of physical restraint use was 3.51% (95%CI = 2.79–4.37%). Physical restraint use was more common in night shifts than day shifts: 4.40% vs. 2.56% (P = 0.03). Male gender, dependency, invasive ventilation, invasive tubes (nasogastric tube or urine catheter), and bedsores were all significantly correlated with restraint use. Staff-to-patient ratios were not significantly correlated with use of physical restraints.

Conclusions: Physical restraints are relatively common in acute care wards. The use of physical restraints seems to correlate with certain patient characteristics but not with staff-to-patient ratios, and seems more common at night. 

 

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Objectives: To examine the effect of seasonality, weather and holidays on hip fracture incidence in older adults. The study population comprised 2050 patients aged 65 years or more who sustained a proximal hip fracture.

Methods: The computerized files of the patients were reviewed for trends in incidence by season, precipitation, minimum and maximum temperatures, day of the week, and certain Jewish festivals.

Results: Hip fractures were more likely to occur in the winter than in the summer (P < 0.0001). Factors that significantly correlated with hip fracture were the maximum daily temperature (r = -0.746, P = 0.005) followed by the minimum daily temperature (r = -0.740, P = 0.006) and precipitation (r = 0.329, P = 0.02). There were fewer fractures on Saturdays (the Sabbath) as compared to other days of the week (P = 0.045). Researching the incidence on Jewish festivals, we found an elevated incidence on Passover (P < 0.0001) and a reduced incidence on the Day of Atonement (Yom Kippur) (P = 0.013).

Conclusions: In older people there is an elevated incidence of proximal hip fractures during the winter and on the Jewish festivals. On weekends and on the Day of Atonement the incidence of proximal hip fractures was reduced.