Israel Medical Association Journal

Background: Statins have anti-inflammatory effects that are independent of their lipid-lowering activity.

Objectives: To examine whether prior statins therapy affects the clinical course of the first episode of acute idiopathic pericarditis (AIP) as the 1-year recurrence and length of hospitalization (LOH).

Methods: This retrospective study included 148 subjects with first episode AIP admitted between the years 2015 and 2019. Data were collected from two hospitals in Northern Israel. We divided the patients in into two groups: 117 those without statins use and 31 those with prior statins use. We compared age, sex, co-morbidities, drugs, laboratory data, 1-year recurrence, and LOH.

Results: The mean age of participants was 43.1 ± 19.4 years. Comparisons between subjects without statins and with prior statins use were made according to age (37.5 ± 16.7 years vs. 64.4 ± 12.7 years, P < 0.01), C-reactive protein (50 ± 40 vs. 48 ± 35 mg/dl, P = 0.9), LOH (5.4 ± 2.85 vs. 8.03 ± 4.92 days, P < 0.01), 1-year recurrence of pericarditis (23 vs. 6 cases, P = 0.95), respectively. Multivariate logistic regression analysis revealed that 1-year recurrence (odds ratio [OR] 0.8, 95% confidence interval [95%CI 0 0.6–1.1, P = 0.41), was not associated with prior statin use, while LOH (OR 2.56, 95%CI 2.08–2.75, P = 0.01) was prolonged with prior statins use in patients with first episode of AID.

Conclusions: Prior statins use in patients with the first episode of AIP did not reduce the 1-year recurrence of pericarditis and prolong the LOH.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4–14) vs. 8 hours (range 4–18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Background: Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.

Objectives: To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.

Methods: A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.

Results: The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).

Conclusions: Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.

Background: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking.

Objectives: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents.

Methods: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses.

Results: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability.

Conclusions: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.

Myelodysplastic syndrome (MDS) is frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory responses of the immune system. The biological linkage between MDS clones and the occurrence of autoimmune manifestations is mirrored by the response of the latter to MDS modifying therapeutic approaches [1]. We encountered a rare case of MDS coexisting with antiphospholipid syndrome (APS), which was effectively treated with a hypomethylating agent followed by allogenic bone marrow transplantation.

Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response.

Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry

Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts.

Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5–57) months.

Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Background: Traditionally, the task of health promotion and early detection screening has been the purview of health maintenance organizations through the family physician. For some years, it has become popular for private health organizations to offer a concentrated day of comprehensive medical testing, which is promoted as a perk by many organizations to their employees. What do these programs offer? Are the tests that are offered evidence based?

Objectives: To describe a concentrated day of comprehensive medical testing program in view of current evidence base medicine (EBM) recommendations.

Methods: We reviewed official internet sites of the most popular concentrated days of comprehensive medical testing and compared the tests offered to the recommendation of several Israeli and international guidelines.

Results: Many tests performed at director screening days do not follow EBM recommendations. Tests like mammography, colonoscopy, bone density, and prostate-specific antigen tests are often offered outside of the recommended age and risk groups and without pretest consultation.

Conclusions: We recommend against routine general health examinations for healthy adults. The most important treatment is not screening and early detection but real prevention. We recommend turning these director screening days into real investments in future health by changing the focus from diagnosis to treatment through prevention. One-on-one conversations, explanations, and most importantly tools to encourage lifestyle changes, will really make a difference.

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: The reduced immune response of maintenance hemodialysis patients to coronavirus disease 2019 (COVID-19) vaccines is a major concern.

Objectives: To analyze the late (6 months after full vaccination) antibody response and compare it to early post-vaccination titer.

Methods: We conducted a multicenter prospective study of 13 hemodialysis units in Israel.

Results: We demonstrated that the low titers observed among ESRD patients 2–3 months after vaccination with the Comirnaty vaccine (median 63.8 AU/ml) declined to critically lower values 6 months after full vaccination. (Mediananti S antibodies, 31 AU/ml). Seropositivity significantly declined among hemodialysis patients from 89% to 74% (P < 0.0001), although it did not significantly change among controls.

Conclusions: We recommend all patients on hemodialysis receive a booster COVID-19 vaccine 6 months after the second dose.

Background: Hookah smoking is a common activity around the world and has recently become a trend among youth. Studies have indicated a relationship between hookah smoking and a high prevalence of chronic diseases, cancer, cardiovascular, and infectious diseases. In Israel, there has been a sharp increase in hookah smoking among the Arabs. Most studies have focused mainly on hookah smoking among young people.

Objectives: To examine the association between hookah smoking and socioeconomic characteristics, health status and behaviors, and knowledge in the adult Arab population and to build a prediction model using machine learning methods.

Methods: This quantitative study based is on data from the Health and Environment Survey conducted by the Galilee Society in 2015–2016. The data were collected through face-to-face interviews with 2046 adults aged 18 years and older.

Results: Using machine learning, a prediction model was built based on eight features. Of the total study population, 13.0% smoked hookah. In the 18–34 age group, 19.5% smoked. Men, people with lower level of health knowledge, heavy consumers of energy drinks and alcohol, and unemployed people were more likely to smoke hookah. Younger and more educated people were more likely to smoke hookah.

Conclusions: Hookah smoking is a widespread behavior among adult Arabs in Israel. The model generated by our study is intended to help health organizations reach people at risk for smoking hookah and to suggest different approaches to eliminate this phenomenon.

Hypertension and cancer are both common due to the aging of the population and the advances in medical treatment which result in increased survival of cancer patients today. More patients with cancer; therefore, present with hypertension, which is attributed to different factors, including genetics and age as well as the type of tumor and cancer-related treatments. Given the increased cardiovascular and mortality risk related to hypertension, it is important to appropriately identify and treat hypertension, particularly in the population of vulnerable cancer patients. In this article we discuss the epidemiology, different etiologies, and approaches to the management of hypertension in cancer patients.

Background: Identifying and treating patients with fragility fractures may be effective in prevention of subsequent fractures because a first fragility fracture often predicts a second fracture.

Objectives: To evaluate a multidisciplinary anti-osteoporotic clinic for patients with prior distal radius fragility fractures (DRFF). To assess whether addressing this early fracture may prevent a second fracture.

Methods: A retrospective case-control study was performed. Cases included patients treated surgically for DRFF who were assessed at a tertiary, multidisciplinary, fracture-prevention clinic. Controls were a series of similarly treated patients who did not attend the clinic. The primary outcome measure was a second fracture.

Results: Average follow-up was 42 months for the treated group and 85 months for the untreated group. The treated group received more treatment for osteoporosis than controls; however, despite one new fracture in the treated group and six new fractures in the control group, there was no significant difference in fracture occurrence.

Conclusions: This pilot study supports the effectiveness of our multidisciplinary anti-osteoporotic clinic in treating osteoporosis but not in reducing subsequent fractures. Further study with larger cohorts and longer follow-up is needed to improve our ability to implement effective prevention of fragility fractures.

Background: Ureteroscopy is becoming the primary treatment for ureteral stones. As a standard of care, ureteroscopy is performed under the supervision of fluoroscopy. Recent advances in endourological technology make the need for fluoroscopy questionable.

Objectives: To summarize our experience with a no-fluoroscopy technique for selected cases of ureteral stones.

Methods: Patients were considered suitable for fluoroless ureteroscopy if they had one or two non-impacted stones, in any location in the ureter, 5–10 mm size, with a normal contralateral renal unit and no urinary tract infection. Procedures were performed using rigid scopes, nitinol baskets/forceps for stone retrieval, and Holmium:YAG laser for lithotripsy. Stents were placed per surgeon's decision.

Results: During an 18-month period, 103 patients underwent fluoroless ureteroscopy. In 94 patients stones were removed successfully. In six, the stones were pushed to the kidney and treated successfully on a separate session by shock wave lithotripsy. In three patients no stone was found in the ureter. In five patients, miniature perforations in the ureter were noted and an indwelling double J stent was placed.

Conclusions: Fluoroless ureteroscopy resulted in a high rate of success. We believe that in selected cases it can be used with minimal adverse events

Background: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered.

Objectives: To describe our experience with surgery of high-risk patients and SRP.

Methods: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes.

Results: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed.

Conclusions: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.

Background: For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation.

Objectives: To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR.

Methods: Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used.

Results: In the study 140 patients with II–III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets.

Conclusions: We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.