Regev Landau MD, Ana Belkin MD, Sapir Kon-Kfir MD, Nira Koren-Morag PhD, Avishay Grupper MD, David Shimunov MD, Ben-Ami Sela PhD, Ehud Grossman MD, Gadi Shlomai MD, Avshalom Leibowitz MD
Background: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients.
Objectives: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment.
Methods: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization.
Results: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change.
Conclusions: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.
Rivka Sheinin MD, Ana Rita Nogueira MD, Nicola L. Bragazzi MD PhD, Abdulla Watad MD, Shmuel Tiosano MD, Tal Gonen MD, Kassem Sharif MD, Yehuda Kameri MD PhD, Howard Amital MD MHA, Daniela Amital MD MHA, Hofit Cohen MD
Background: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia.
Objectives: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not.
Methods: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population.
Results: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia.
Conclusions: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.
Bar Pitaro Alter MD, Shmuel Tiosano MD, Yuval Kuntzman MD, Omer Gendelman MD, Guy Shalom MD, Abdulla Watad MD, Howard Amital MD MHA, Arnon D. Cohen MD MPH, Daniela Amital MD MHA
Backgrounds: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression.
Objectives: To evaluate the association between BD and depression, adjusting for established risk factors for depression.
Methods: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex.
Results: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37–2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39–2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18–39 years of age), low and high socioeconomical status, and non-smokers.
Conclusions: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.
Katya Meridor MD, Pnina Rotman-Pikielny MD, Or Carmi MD, Myriam Werner MD, Yair Levy MD
Background: Patients with systemic sclerosis (SSc) are at increased risk for autoimmune thyroid diseases, but information regarding thyroid nodules and cancer in SSc is scarce.
Objectives: To evaluate the thyroid gland in patients with SSc at a single Israeli center.
Methods: Thyroid workup was conducted in consecutive SSc patients: thyroid-stimulating hormone (TSH), free thyroxine (fT4), anti-thyroid peroxidase, and anti-thyroglobulin antibodies, as well as thyroid ultrasound and fine needle aspiration (FNA) when appropriate.
Results: Fifty patients, mean age 51.3 ± 13.5 years (44 women) were evaluated. Ten were previously diagnosed with thyroid disease. Median TSH level was 2.0 (normal range 0.23–4 mIU/l) and median fT4 level was 1.0 (normal range 0.8–2.0 ng/dL). Among the 40 thyroid disorder-naive patients, 3 had subclinical hypothyroidism and 5 had positive anti-thyroid antibodies; 22 (44%) had 1–6 thyroid nodules, which were ≥ 1 cm in 12 (24%). Accordingly, six patients underwent FNA, and five were diagnosed as colloid nodules and one as papillary carcinoma.
Conclusions: New cases of clinically significant autoimmune thyroid disease were not detected in our cohort of patients with SSc. Nevertheless, almost half had thyroid nodules. The clinical significance of these findings and their relation to thyroid cancer remains to be determined.
Adi Lichtenstein MD, Shmuel Tiosano MD, Doron Comaneshter MD, Arnon D. Cohen MD, Howard Amital MD
Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and tenderness with associated neuropsychological symptoms such as fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Osteoporosis is defined as a reduction of bone density. Previous studies to determine an association of FMS with osteoporosis showed mixed results, partially due to small sample sizes and lack of statistical power.
Objectives: To evaluate the association of FMS with osteoporosis.
Methods: We conducted a case-control study utilizing the database from Israel’s largest health maintenance organization. FMS patients were compared to age- and sex-matched controls. Data were analyzed using chi-square and t-tests. Multivariable logistic regression models assessed the association between osteoporosis and FMS. Spearman’s rho test was used for correlation.
Results: We utilized data from 14,296 FMS patients and 71,324 age- and sex-matched controls. Spearman's rho test showed a significant correlation between FMS and osteoporosis (correlation coefficient 0.55, P < 0.001). A logistic regression for osteoporosis showed an odds ratio [OR] of 1.94 (95% confidence interval [95%CI] 1.83–2.06, P < 0.001) for FMS compared to controls and found higher body mass index to be slight protective (OR 0.926, 95%CI 0.92–0.93, P < 0.001).
Conclusions: There is a significant correlation between FMS and osteoporosis. Early detection of predisposing factors for osteoporosis in FMS patients and implementation of suitable treatments and prevention measures (such as dietary supplements, resistance or weight bearing exercise, and bone-mineral enhancing pharmacological therapy) may reduce both occurrence rate and severity of osteoporosis and its complications, such as fractures.
Niv Izhaki MD, Shay Perek MD, Mahmoud Agbaria BSc, Ayelet Raz-Pasteur MD
Pneumonia patients are susceptible to autonomic nervous system changes. Ultrashort HRV (usHRV) is the measurement of cyclic changes in heart rate over a period < 5 minutes.
Objectives: To describe usHRV in patients with pneumonia and assess the correlation with mortality.
Methods: We conducted a retrospective analysis, which included patients diagnosed with pneumonia in the emergency department (ED). UsHRV indices were calculated from a 10-second ED electrocardiogram and correlated with mortality utilizing logistic and Cox regressions.
Results: The study comprised 240 patients. Mortality rates over 30, 90, and 365 days were 13%, 18%, and 30%, respectively. usHRV frequency-domain parameters had significant univariate correlations with mortality. Normalized low frequency (LF) and high frequency (HF) were correlated with 30-, 90-, and 365-day mortality in an opposite direction (odds ratio [OR] 0.094, P = 0.028 vs. OR 4.589, P =0.064; OR 0.052, P = 0.002 vs. OR 6.975, P =0.008; OR 0.055, P < 0.001 vs. OR 7.931, P < 0.001; respectively). Survival analysis was conducted for a follow-up median period of 5.86 years (interquartile range 0.65–9.77 years). Univariate Cox proportional hazard regression revealed time-domain indices with significant correlation with survival (SDNN and RMSSD; hazard ratio [HR] 1.005, 1.005; P = 0.032, P = 0.005; respectively) as well as frequency-domain parameters (normalized LF, HF, LF/HF ratio, and total power; HR 0.102, 5.002, 0.683, 0.997, respectively; P < 0.001).
Conclusions: usHRV may predict mortality in pneumonia patients and serve as a novel risk stratification tool.
William Nseir MD, Lior Masika MD, Adi Sharabi-Nov MD, Raymond Farah MD
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.
Johad Khoury MD, Itai Ghersin MD, Eyal Braun MD, Adi Elias MD, Doron Aronson MD, Zaher S. Azzam MD, Fadel Bahouth MD
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.
Avishay Elis MD, Wassim Daud MD, Gal Cohen MD, Ela Giladi MD, Alaa Atamna MD
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.
Moriah Bergwerk MBBS, Nir Lasman MD, Limor Helpman MD, Barak Rosenzweig MD, Dor Cohen MD, Edward Itelman MD, Raz Gross MD, Gad Segal MD
Worldwide, students of healthcare professions attend clinical rotations at medical facilities. Much research, and consequently scientific publications, is produced during their studies, bearing the fruits of student–faculty collaboration. To the best of our knowledge, no previous contract has been proposed detailing the fine print to pre-determine mutual responsibilities and privileges of students and faculty. Our objective was to present such a contract to the relevant students and faculty. We conducted a literature review to study existing proposals and solutions for this dilemma. Appropriate guidelines were also scanned. We included a proposal for a standard contract as the basis for student–faculty agreement for conducting research and publishing collaborative work. Questions regarding the relative contribution of students and subsequent authorship often arise. Vague rules and absent regulations in this realm can, at times, can be disadvantageous to students. We foresee a future role for our proposed agreement.
Lior Fisher MD, Howard Amital MD MHA, Orly Goitein MD
Mesenteric venous thrombosis (MVT) refers to acute, subacute, or chronic thrombosis and occlusion of the mesenteric veins. MVT is an uncommon disorder, with an estimated incidence of is 2.7 per 100,000 patient-years. It accounts for 1 in 5000 to 15,000 inpatient admissions [1,2].
David Levy MD, Mayan Eitan MD, Mark Vitebskiy MD, Yona Kitay-Cohen MD, Fabiana Benjaminov MD
A 70-year-old male arrived at the emergency department (ED) with symptoms of fever, shivering, and sweating for 3 days. A dry cough started a week before admission. There were no other referring symptoms. The patient, a farmer by occupation, denied any animal bite or exposure, travel abroad, consumption of uncooked meat, or drink of unpasteurized milk products. In the ED, his vital signs showed hypotension with blood pressure of 70/40 mmHg, pyrexia of 39.4°C, and tachycardia of 100 beats per minute. On physical examination, the patient shivered. On auscultation, fast heart sounds were heard.
Shada Azem MD, Roy Raphael MD, Shir Raibman-Spector MD, Kobi Faierstein MD, Amir Givon MD, Haim Mayan MD
Intravesicular administration of Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has long been used as adjuvant therapy for treatment of non-muscle invasive bladder carcinoma. BCG is usually well tolerated; however, infectious complications can range from 1–5% of cases. Infectious complications of BCG [1] can be divided into localized disease, which is considered a late onset disease occurring 3 months following treatment such as cystitis, Epididymo-orchitis, and pyelonephritis. Another form is a systemic disease, which is an early onset manifestation including sepsis syndrome that usually occurs directly after treatment and is the most common form of disseminated BCG infection.
Shirley Shapiro MD, Shira Shoher MD, Dror Cantrell MD, Micha J. Rapoport MD
Retroperitoneal infiltration, also known as retroperitoneal fibrosis (RPF), is a rare condition, which mostly occurs in men over the age of 40 years. This condition involves inflammation of the soft tissue of the retroperitoneal cavity, most commonly around the infrarenal abdominal aorta, iliac arteries, ureters, and abdominal organs. Clinical manifestations consist of severe pain in the lower back, abdomen, or flank, which may radiate to the inguinal region. Pain may be acute at the onset and can be mistaken for renal colic. Renal and ureteral involvement is common and can develop into acute kidney injury and hypertensive crises.
Ela Giladi MD, Adi Rotkopf MD, Avishay Elis MD
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.