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Fri, 22.11.24

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November 2022
Izabella Elgardt MD, Or Carmi MD, Yair Levy MD

At the end of 2019, the world faced a new virus–coronavirus disease 2019 (COVID-19)–which quickly became a pandemic. It has become clear that the COVID-19 virus can affect various body systems. Over time, we are finding more and more diverse manifestations of the course of the disease itself, its consequences, and complications. There have been several studies and reviews describing circulating antibodies in patients infected with COVID-19 (e.g., antinuclear antibodies [ANA], anti-cardiolipin, anti-B2 glycoprotein, perinuclear anti-neutrophil cytoplasmic antibodies [p-ANCA], cytoplasmic ANCA [c-ANCA]). The development of autoimmune disorders has been reported (e.g., Graves' disease, systemic lupus erythematosus (SLE), immune thrombocytopenia [ITP], diabetes mellitus [DM] type 1, psoriasis). There are descriptions of COVID-19 associated vasculitis include Kawasaki-like symptoms in children and immunoglobulin A (IgA) vasculitis in children and adults [1].

Michael Shapiro MD, Yarden Yavne MD, Daniel Shepshelovich MD

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to more than 200 million infected cases and 4.6 million deaths worldwide, and the numbers continue to grow. The disease presentation varies, and while most patients will present with a mild disease course, 5% will eventually develop significant respiratory failure, some despite initially presenting with mild symptoms. Early detection of patients at risk for deterioration is crucial for decisions regarding hospitalization, monitoring, timing, and extent of treatment.

Zvia Agur PhD

The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on our world and has cost millions their lives. It has disrupted economies and education systems and has taken away means of support from masses of people around the world. No wonder this pandemic is like a black hole, drawing in all resources and all expertise. In the scientific arena, the pandemic has created a tremendous opportunity for new and exciting synergies between different disciplines.

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.

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.

Yehonatan Sherf MD MPH, Dekel Avital MD, Shahar Geva Robinson MD, Natan Arotsker MD, Liat Waldman Radinsky MD, Efrat Chen Hendel MD MPH, Dana Braiman MD, Ahab Hayadri MD, Dikla Akselrod MD, Tal Schlaeffer-Yosef MD, Yasmeen Abu Fraiha MD, Ronen Toledano MD, Nimrod Maimon MD MHA

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.

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.

October 2022
Shaden Nashashibi, MD, Ofir Priesler, MD, Uriel Levinger, MD, George Habib, MD MPH

The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than four million deaths globally. In addition to the lower respiratory system, a wide range of major organ injuries have been reported among patients infected with COVID-19. These injuries include cardiac involvement. The spectrum of cardiac manifestations includes cardiac injury, heart failure, cardiogenic shock, acute coronary syndrome, myocarditis, tachyarrhythmias, and bradyarrhythmia [1]. Different degrees of atrioventricular blocks have been reported [2].

The pathogenesis of these complications is not fully understood. Differentmechanisms are proposed, including direct myocyte injury, interstitial inflammation and fibrosis, cytokine storm, plaque destabilization, and and/or hypoxia [3]. Many countries have worked toward mass vaccination using the Pfizer BioNTech (BNT162b2) COVID-19 vaccine, including Israel. We report a case of high degree atrioventricular block (AVB) following vaccination with the COVID-19 BNT162b2 vaccine.

Adrian Duek MD, Emmanuel Lellouche PhD, Sharon Ben Baruch MD, Reut Mashiach BSc, Yafit Segman MD, Gabriel Bryk PhD, Merav Leiba MD

Background: Multiple myeloma (MM) accounts for approximately 10% of hematological malignancies. The monoclonal immunoglobulin G kappa (IgG-κ) daratumumab can bind to CD38 on MM cells and be detected in serum immunofixation (IF), causing pitfalls in M-protein quantification.

Objectives: To determine the efficacy of mitigating the interference of IgG MM treated with daratumumab.

Methods: Levels of Ig, free light chains (FLC) kappa (κ) and lambda (λ), serum protein electrophoresis (SPE)/IF, and Hydrashift 2/4 assays were assessed following manufacturer's instructions in three patients.

Results: Patient 1 was a 70-year-old male diagnosed with IgG-λ MM. The IF distinguished two monoclonal bands (IgG-κ and IgG-λ). With the Hydrashift assay, the daratumumab–anti-daratumumab immune complex shifted the IgG-κ to the α zone, suggesting that the monoclonal IgG-κ band corresponded to daratumumab. Patient 2 was a 63-year-old male with IgG-κ MM who was receiving daratumumab once every other week. SPE/IF assay revealed a faint monoclonal IgG-κ band in the g zone. A stronger monoclonal band was observed after administration. The IgG-κ band disappeared on the Hydrashift assay, while the daratumumab–anti-daratumumab complex appeared as a broad smear in the α-region. Patient 3, a 63-year-old male diagnosed with IgG-λMM, was receiving daratumumab once every other month. The IF assay showed two distinct bands (IgG-κ and IgG-λ) post-daratumumab administration. The shift to the α zone of the IgG-κ bands on the Hydrashift assay confirmed that the additional band observed post-infusion was due to the daratumumab.

Conclusions: The Hydrashift assay can help distinguish daratumumab from endogenous M-spike.

Ron Skorochod B.MED.SC, David Raveh MD, Yonit Wiener-Well MD, Bashar Fteiha MD, Shimon Shteingart PhD, Yitzhak Skorochod MD

Background: The hepatobiliary system is a sterile micro-environment. Bacterial infection in this system is most commonly associated with anaerobes as well as gram-positive and gram-negative bacteria. Biliary infections with Staphylococcus aureus are poorly characterized.

Objectives: To depict the clinical characteristics and outcome of patients with S. aureus infection of the hepatobiliary system.

Methods: Medical records of patients with bile cultures positive for S. aureus from January 2006 to November 2020 were extracted from the computerized database of a hospital in Israel.

Results: We analyzed the results of 28 cases that were found in the database. The mean age of study patients was 62.2 ± 19 years. Hypertension, dyslipidemia, chronic kidney disease, diabetes, and benign prostatic hypertrophy were the most common co-morbidities (57.1%, 32.1%, 25%, 25%, and 25%, respectively). Fourteen of the methicillin-resistant S. aureus (MRSA) bile cultures (82.3%) were a result of primary S. aureus biliary infections (no other source for S. aureus infection) and the remainder were of a secondary infection. Eight of the MRSA cultures (47.1%) were from hospital acquired infections. Increased hospital mortality in patients with S. aureus hepatobiliary infection was associated with hypertension (P = 0.04), bedridden status (P = 0.01), and nursing home residence (P = 0.003).

Conclusions: Hepatobiliary infection with S. aureus can manifest in a variety of ways. S. aureus should be especially considered in patients who are bedridden, present with hypertension, or live in nursing homes because of their association with in-hospital mortality resulting from this entity.

Ofira Zloto, M.D., Oded Sagiv, M.D., Ayelet Priel, M.D., Tali Cukierman-Yaffe, M.D., Amir Tirosh, M.D. , Nancy Agmon-Levin, M.D., Shiran Madgar, M.D., Tal Serlin, M.D., Halit Winter, M.D. Ruth Huna-Baron, M.D., Tamara Wygnanski-Jaffe, M.D., Guy Ben Simon, M.D.

Background: Little is known about the success of multidisciplinary thyroid eye disease (TED) clinic.

Objectives: To present the characteristics, treatments, and outcomes of patients treated in a multidisciplinary TED clinic.

Methods: A medical record review of all patients who attended a TED clinic was performed. Data included demographics, medical history, laboratory tests, visual function tests, ocular examinations, clinical activity score (CAS), and assessment of quality-of-life (QOL).

Results: Clinic visits included 132 patients seen during 385 appointments at a TED clinic (mean 12 appointments per patient). Management of TED included medical treatments for 48 patients (36.3%) and surgical treatment for 56 (42.4%). There was a positive significant correlation between the CAS and thyroid-stimulating immunoglobulin (TSI) activity at the first visit and at the last follow-up visit (P < 0.01 and P < 0.02, respectively). However, no correlation was found between the CAS and the thyroid-stimulating hormone levels or between the free triiodothyronine (fT3) and fT4 levels at the first or last visit. There was a significant negative correlation between the CAS and color vision (-0.347, P < 0.01, Pearson correlation) at the first visit, but not between the CAS and visual acuity and visual field at either the first or last visit. Changes in the QOL and the CAS scores were significantly negatively correlated (-0.240, P < 0.01).

Conclusions: Treatment and management decisions for TED should be based on multiple parameters including clinical examinations by ophthalmologists and endocrinologists, laboratory tests, and CAS and QOL scores.

Ahmad Elnassasra, MD; Yehuda Hershkovitz, MD ; Yaniv Zager, MD; Ron Lavy, MD;
Walid Shalata MD, Motaz Abo Abod MD, Sergei Tsaregorodtsev MD, Reem Abu Hamid-Salama MD, Liora Boehm Cohen MD, Michael Kassirer MD, Dana Potashner MD, Yael Raviv MD
September 2022
Avi Benov MD MHA, Shaul Gelikas MD MBA, Noam Fink MD, and Elon Glassberg MD MHA MBA

War is as old as history. Some may say it is older. The first Biblical war, dated 1880–1875 BCE, is depicted in the book of Genesis between nine kings in the vicinity of the Jordan river near Jericho. By the end of the war, Abraham (Abram) gets involved in saving his nephew Lot.

In addition to war, military medicine also has its roots in historical times. Hippocrates (460–377 BCE), the father of medicine, derived his medical knowledge from the battlefield, and Sushruta [1], the father of plastic surgery, mentioned the physician's preventive role in noting environmental hazards: "A common practice of the enemy is to poison the wells on the roadside, the articles of food, the shades of trees, and the fuel and forage for cattle; hence, it is incumbent on a physician marching with the troops to inspect, examine, and purify these before using any of them, in case they are poisoned."

The Greeks stated new ideas of military health, pointing to fitness promotion, gymnastics, and healthy diets to prevent illness. Over the centuries, from Alexander the Great to Napoleon’s army and wars in the 20th century, military conflicts have led to the death of hundreds of millions of people from trauma and war-related disease. Amazingly analyses of the 18th and 19th centuries have shown that 80% of the soldiers died from disease, and historians and military personnel agree that during armed conflicts in known history, only a minority of soldiers perished by the sword.

In Israel, the Israel Defense Forces-Medical Corps (IDF-MC) holds a unique position embedded in military and civilian national medicine. All medical personnel (e.g., physicians, nurses, technicians, veterinarians) who work in the IDF-MC receive their diplomas from civilian universities, train in civilian hospitals, and continue to practice in the national health system. The majority of these professionals continue to work in different civilian medical platforms in Israel after finishing their mandatory service. The IDF-MC's primary mission is to provide optimal medical care to IDF soldiers at all times (including wartime), to prevent disease and promote health, advance military medicine, and aid the civilian sector as ordered by the Government of Israel.

In this special issue of Israel Medical Association Journal (IMAJ) is to expose readers to the continuous efforts of the IDF-MC to fulfill its mission by promoting research in multiple medical fields, including trauma, ambulatory care, health administration. In addition, in this issue of IMAJ, authors discuss the unique collaboration with the civilian system during the coronavirus disease 2019 (COVID-19) pandemic.

Trauma and trauma-related injuries are the main focus of military medical research. Ben-Avi and colleagues [2] described outcomes of emergent exploratory thoracotomies on military casualties and addresses parameters that may impact the survival of these casualties. Minervini [3] further discussed the issue. Bez et al. [4] researched the impact of isolated versus non-isolated traumatic brain injuries on injury identification and decision-making by care providers in austere scenarios. Tsur and co-authors [5] described the characteristics of a unique type of terror attack: vehicle ramming.

Additional examples of treatments provided in the military prehospital arena were analyzed by Nakar and colleagues [6] who discussed how to assess pain medications administered to trauma casualties in the past two decades by IDF-MC care providers. Rittblat et al. [7] further described the use of freeze-dried plasma, a blood component used in the prehospital arena and administered via intraosseous vascular access.

The IDF-MC is a continuously changing organization emphasizing the adoption of advanced technologies and devices. Chen et al. [8] presented a blinded study on the use of point-of-care ultrasound and remote telementored ultrasound by inexperienced operators, and Sorkin et al. [9] described the BladeShield 101: a novel device for the battlefield designed to continuously measure vital signs and medical treatment provided and to transfer data through roles of care.

In this special issue of IMAJ, authors also discusse gender-related aspects at the core of medical treatment. Segal et al. [10] examined whether missed injuries were related to the medical provider's gender, while Gelikas et al. [11] assessed whether treatment with analgesia was associated with casualty gender in the military prehospital trauma setting

Over the past two and a half years, the COVID-19 pandemic has been a significant part of our lives. During these years, medical systems and teams throughout Israel and around the world struggled to adapt to this new disease and save lives fighting the pandemic. Geva et al. [12] and Shental et al. [13] discussed the impact of COVID-19 on the IDF medical system, lessons learned during the outbreak, and effects of different diseases during these times on medical treatment provided by the IDF to soldiers.

Gil A. Geva MD, Maya Nitecki MD, Itay Ketko MSc, Itay Toledo BSc, Sagi A. Shpitzer MD, Avi Benov MD MHA, Noam Fink MD, and Ariel Furer MD MBA

Background: To mitigate the spread of coronavirus disease 2019 (COVID-19), national guidelines, in accordance with international health authorities, mandated 14 days of quarantine for every close contact of a confirmed COVID-19 patient. Although health benefits are obvious, consequences are profound, especially for organizations required to maintain operational preparedness.

Objectives: To present the Israel Defense Force (IDF) experience with outbreaks regarding quarantined individuals. To weigh the consequences of quarantined individuals needed for workforce and operation.

Methods: All positive COVID-19 cases in the IDF, as measured by a positive rRT-PCR test result, between 29 February and 18 May 2020 were evaluated. Numbers of positive individuals, quarantined individuals, and confirmatory exams conducted were collected. We compared the events in four units with the largest outbreaks and assessed the impact of confirmed cases, tests conducted, and workforce loss due to quarantine.

Results: Of the 187 soldiers who tested positive for COVID-19, source of infection was traced to 140 soldiers (75%). Almost no medical treatment was delivered, and hospitalization was rare. We found a median of 15.2% (interquartile range 5.3–34) for decline in unit workforce due to quarantine measures. Maximum reduction reached 47% of the workforce in one unit.

Conclusions: Despite a relatively small number of confirmed cases, units underwent a substantial change in mode of operation due to the toll of quarantined individuals. In certain populations and organizations, perhaps a more liberal application of isolation and contact tracing is suitable due to the heavy economic burden and consequences in term of operational readiness.

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