Israel Medical Association Journal

Background: There has been a rapid increase in vulnerable subpopulations of very old with co-morbidity, dementia, frailty, and limited life expectancy. Being treated by many specialists has led to an epidemic of inappropriate medication use and polypharmacy (IMUP) with negative medical and economic consequences. For most medications there are no evidence-based studies in older people and treatments are based on guidelines proven in much younger/healthier populations.

Objectives: To evaluate whether the benefits of reducing IMUP by poly-de-prescribing (PDP) outweighs the negative outcomes in older people with polypharmacy.

Methods: The Garfinkel method and algorithm were used in older people with polypharmacy (≥ 6 prescription drugs).

Results: We found that in nursing departments, of 331 drugs de-prescribed only 32 (10%) had to be re-administered. Annual mortality and severe complications requiring referral to acute care facility were significantly reduced in PDP (P < 0.002). In community dwelling older people, successful de-prescribing was achieved in 81% with no increase in adverse events or deaths. Those who de-prescribed ≥ 3 prescription drugs showed significantly more improvement in functional and cognitive status, sleep quality, appetite, serious complications, quality of life, and general satisfaction compared to controls who stopped ≤ 2 medications (P < 0.002). Rates of hospitalization and mortality were comparable. Clinical improvement by polydeprescribing was usually evident within 3 months and persisted for several years. The main barrier to polydeprescribing was physician’s unwillingness to deprescribe (P < 0.0001)

Conclusions: Applying the Garfinkel method of PDP may improve the lives of older people and save money.

Background: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results.

Objectives: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2).

Methods: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression.

Results: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29–0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27–0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16–0.95) were analyzed separately.

Conclusions: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value.

Objectives: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients.

Methods: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality.

Results: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09–1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure.

Conclusion: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Background: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited.

Objectives: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC.

Methods: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist.

Results: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7–7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1–12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1–5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9–26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2–not reached).

Conclusions: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC. 

Background: Patients with right bundle branch block (RBBB) prior to transcatheter aortic valve implantation (TAVI) are at high risk for immediate post-procedural heart block and long-term mortality when discharged without a pacemaker.

Objectives: To test whether prophylactic permanent pacemaker implantation (PPI) is beneficial.

Methods: Of 795 consecutive patients who underwent TAVI, 90 patients had baseline RBBB. We compared characteristics and outcomes of the prophylactic PPI with post-TAVI PPI. Need for pacing was defined as  greater than 1% ventricular pacing.

Results: Forty patients with RBBB received a prophylactic PPI (group 1), and in 50 the decision was based on standard post-procedural indications (group 2). There were no significant differences in clinical baseline characteristics. One patient developed a tamponade after a PPI post-TAVI. A trend toward shorter hospitalization duration in group 1 patients was observed (P = 0.06). On long-term follow-up of 848 ± 56 days, no differences were found in overall survival (P = 0.77), the composite event-free survival of both mortality and hospitalizations (P = 0.66), or mortality and syncope (P = 0.65). On multivariate analysis, independent predictors of the need for pacing included baseline PR interval increase of 10ms (odds ratio [OR] 1.21 per 10 ms increment 95% confidence interval [95%CI] 1.02–1.44, P = 0.028), and the use of new generation valves (OR 3.92, 95%CI 1.23–12.46, P = 0.023).

Conclusions: In patients with baseline pre-TAVI RBBB, no outcome differences were found with prophylactic PPI. On multivariate analysis, predictors of the need for pacing included baseline long PR interval, and the use of newer generation valves.

Background: Transcatheter tricuspid valve-in-valve implantation (TVIV) is an attractive yet under-explored alternative to redo valve surgery. 

Objectives: To report the multicenter TVIV experience in Israel.

Methods: We approached multiple centers and collected data regarding seven TVIV cases. 

Results: The study group comprised seven participants: five females and two males, with a mean age of 63 ± 12 years and EuroSCORE-II 13.6 ± 3.3%. Follow-up ranged from 3 to 21 months (mean 8 ± 6 months). All presented with advanced heart failure. The indication for valve intervention was a predominant tricuspid stenosis in three patients, significant tricuspid regurgitation in one and a mixture in three. Six procedures were conducted via a transfemoral approach and one by transatrial access. The Edwards SAPIENTM XT valve was used in four cases and the SAPIENTM 3 in three. Without pre-stenting/rapid pacing, all participants underwent successful valve implantation. Mean transvalvular gradient decreased from 11 ± 3 mmHg to 6 ± 3 mmHg (P = 0.003) and regurgitation decreased from moderate/severe (in four cases) to none/trace (in six of the seven cases). One patient remained severely symptomatic and died 3.5 months after the implantation. All others achieved a functional capacity improvement and amelioration of symptoms soon after the implantation, which persisted during follow-up. 

Conclusions: TVIV may be a safe and effective strategy to treat carefully selected patients with degenerated bioprosthetic tricuspid valve at high operative risk. 

 

Background: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable.

Objectives: To evaluate the association of biomarkers with coronary and carotid disease.

Methods: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery. Biochemical markers of cardiovascular disease risk were obtained at the time of coronary angiography, including serum lipid levels, hemoglobin A1C (HbA1c), white blood cell count, fibrinogen and high sensitivity C-reactive protein (hs-CRP).

Results: The mean age of the patients was 66 ± 11; 73% were males. Significant carotid stenosis was associated with higher hs-CRP (9.4 ± 17 vs. 6.3 ± 13 mg/L, P = 0.001), while high HbA1c (6.7 ± 1.6 vs. 5.8 ± 0.8%, P < 0.001) and low high density lipoprotein levels (40 ± 9 vs. 47 ± 14 mg/dl, P < 0.001) were linked with advanced coronary artery disease severity. In contrast, CIMT was not related to any of the biomarkers evaluated.

Conclusions: Although atherosclerosis is considered a systemic disease, different biomarkers are associated with coronary and carotid artery disease. Identifying the specific biomarkers for each disease is important for both prevention and for exposing the underlying pathophysiologic mechanism.

 

Background: Anemia confers an adverse prognosis in patients with ST-elevation myocardial infarction (STEMI). Several mechanisms have been implicated in the etiology of anemia in this setting, including inflammation, blood loss, and the presence of comorbidities such as renal failure.

Objectives: To evaluate the adequacy of bone marrow response as potentially reflected by elevation in blood and reticulocyte counts.

Methods: Consecutive men with STEMI who underwent primary percutaneous intervention within 6 hours of symptom onset and who presented to our catheterization laboratory during a 36 month period were included in the study. The cohort was divided into quartiles according to hemoglobin concentration, and differences in clinical and laboratory characteristics between the groups were evaluated.

Results: A total of 258 men with STEMI were recruited, 22% of whom suffered from anemia according to the World Health Organization classification (hemoglobin < 13 g/dl). Men in the lowest quartile of hemoglobin concentration presented with significantly lower white blood cell and platelet counts (9.6 ± 2.9 vs. 12.6 ± 3.6 x103/µl, P < 0.001) and (231 ± 79 vs. 263 ± 8 x103/µl, P < 0.01), respectively, despite higher inflammatory biomarkers (C-reactive protein and fibrinogen) compared with patients in the upper hemoglobin concentration quartile. Reticulocyte production index was not significantly higher in anemic patients with a value of 1.8, 1.4, 1.5 and 1.6 in the ascending hemoglobin quartiles, respectively (P = 0.292). 

Conclusions: Anemic men with STEMI have relatively lower leukocyte and platelet counts as well as a reduced reticulocyte count despite higher inflammatory biomarkers. These findings might suggest inadequate bone marrow response. 

 

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

Objectives: To investigate the 30 day clinical outcome of the first 300 consecutive patients treated with transfemoral TAVI at the Tel Aviv Medical Center.

Methods: The CoreValve was used in 250 patients and the Edwards-Sapien valve in 50 patients. The mean age of the patients was 83 ± 5.3 years (range 63–98 years) and the mean valve area 0.69 ± 0.18 cm² (range 0.3–0.9 cm²); 62% were women.

Results: The procedural success rate was 100%, and 30 day follow-up was done in all the patients. The average Euro-score for the cohort was 26 ± 13 (range 1.5–67). Total in-hospital mortality and 30 day mortality were both 2.3% (7 patients). Sixty-seven patients (22%) underwent permanent pacemaker implantation after the TAVI procedure, mostly due to new onset of left bundle brunch block and prolonged PR interval or to high degree atrioventricular block. The rate of stroke was 1.7% (5 patients). Forty-one patients (13.7%) had vascular complications, of whom 9 (3%) were defined as major vascular complications (according to the VARC definition).

Conclusions: The 30 day clinical outcome in the first 300 consecutive TAVI patients in our center was favorable, with a mortality rate of 2.3% and low rates of stroke (1.7%) and major vascular complications (3%).

Objectives: To evaluate the clinical course of four children with cricopharyngeal achalasia presenting to our clinic.

Methods: We conducted a 5 year retrospective chart review in a tertiary referral center.

Results: Four children were diagnosed with primary cricopharyngeal achalasia between 2006 and 2010. Diagnosis was established by videofluoroscopy and all underwent uneventful cricopharyngeal myotomy. Three children recovered completely and one child showed partial improvement. For residual UES spasm in a partially improved patient, botulinum toxin was injected into the UES which led to further improvement. Dysphagia recurred in one child who was successfully treated with botulinum toxin injection.

Conclusions: Cricopharyngeal myotomy is a safe procedure in infants and young children. Botulinum toxin injection of the UES was found to be effective in refractory cases. 

 Background: Burn injuries are extremely common and may impose a serious load on public health around the world.

 Objectives: To compare mortality rates and length of hospitalization according to the identified risk factors, extent of burn, gender and age.

Methods: In this retrospective study, data from 558 archive files of hospitalization due to burns as the diagnosis in patients of all ages, between the years 2001 and 2002, were analyzed to identify the risk factors for mortality and length of hospitalization.

Results: Males comprised 62.4% of the hospitalized burn patients. The mortality rate was 3.2% (n=18) and among them 55.6% were women. Fifty percent of the fatality cases were over 48 years old, with statistically significant correlation of mortality rate and age. Most of the fatality cases (66.7%) had burns with total burn surface area (TBSA) larger than 40%. The multiple logistic regression model showed that leukocyte count on admission, TBSA, and age are the most important predictors of mortality. Smoke inhalation was not found to be an independent risk factor.

Conclusions: Using a statistical model for estimating the mortality rate, this study found that white blood cell count at admission, TBSA, and age were the most significant predictors of mortality. 

Background: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI[1] the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction.

Objectives: To determine the added value of thrombus aspiration prior to primary PCI[2] by comparing AMI[3] patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI.

Methods: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups.

Results: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P = 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although P was not significant). Long-term follow-up total MACE[4] showed a non-significant positive trend in the extraction group (12.96% vs. 24.71%, P = 0.26).

Conclusions: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.