Israel Medical Association Journal

Background: Granulomatosis with polyangiitis (GPA) otologic manifestations include conductive and sensorineural hearing loss (HL). Vasculitis is assumed to be the primary cause of otologic manifestations. Deaf patients and patients with HL who do not benefit from hearing aids can benefit from cochlear implants (CI). There are currently no specific guidelines for treatment of patients with GPA suited for CI.

Objectives: To assess whether patients who are deaf due to GPA are good candidates for CI and if prior surgical or medical treatment of the inflammation are needed.

Methods: A case report is presented.

Results: A 71-year-old female patient with GPA and bilateral profound HL underwent CI. Prior to CI, preparation consisted of audiological evaluations by an otolaryngologist and a rheumatologist, followed by a course of prednisone and methotrexate for middle ear and nasal inflammations. CI was performed with no complications. The speech reception threshold and the monosyllabic word discrimination score after surgery were 25 dBHL and 75%, respectively.

Conclusions: Inflammation due to GPA can be controlled medically with immunosuppressive medications without subtotal petrosectomy, as in chronic suppurative otitis media. Satisfactory audiological results can be expected.

Background: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality.

Objectives: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations.

Methods: Data were collected from all patients under 18 years who met our internal guidelines from 2015–2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample.

Results: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34).

Conclusions: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.

Background: Vaginal hysterectomy (VH) and colpocleisis are both used for the treatment of advanced pelvic organ prolapse (POP).

Objective: To compare short- and long-term outcomes of vaginal hysterectomy vs. colpocleisis for advanced POP.

Methods: Hospital and outpatient charts of patients who underwent VH or colpocleisis at our institution between January 2006 and December 2015 were reviewed. Clinical data were obtained and analyzed.

Results: In this study, 188 patients underwent VH and 32 patients underwent colpocleisis. The colpocleisis group was significantly older than the VH group (79.5 ± 4.5 vs. 69 ± 6.1 years respectively, P < 0.0001) and presented with significantly higher co-morbidity rates and a higher degree of POP. Perioperative blood loss was significantly lower (250 ± 7.6 ml vs. 300 ± 115 ml, P < 0.0001) and postoperative hospitalization was significantly shorter (2 ± 2.7 vs. 3 ± 2.2 days, P = 0.015) among the colpocleisis group. None of the patients from the colpocleisis group required an indwelling urethral catheter after discharge, compared to 27.5% of the patients from the VH group (P = 0.001). Total postoperative complication rate was significantly lower among the colpocleisis group (25% vs. 31% P < 0.0001). Objective recurrence of POP was significantly more common among the VH group (7% vs. 0% and 21% vs. 0% for the anterior and posterior compartments, respectively, P = 0.04).

Conclusions: Colpocleisis is associated with faster recovery, lower perioperative morbidity, and higher success rates than VH and should be considered for frail and elderly patients.

Background: Data regarding risk factors for superficial thrombophlebitis (STP) cases presenting to a hospital is limited.

Objectives: To investigate and stratify clinical and laboratory risk factors for STP

Methods: We conducted a retrospective case control study comparing patients presenting to the emergency department with STP and age- and gender-matched controls. We collected data on multiple risk factors and five blood indices.

Results: The study comprised 151 patients and matched controls. Patients with STP were more likely to have varicose veins (43.7% vs. 5.3%, P < 0.001), recent immobilization (14.6% vs. 1.3%, P < 0.001), obesity (36.4% vs. 18.5%, P = 0.001), a history of venous thromboembolism (VTE) or STP (27.2% vs. 0.7%, P < 0.001), and inherited thrombophilia (9.3% vs. 1.3%, P = 0.002). Following multivariate analysis, all five risk factors remained significant, with a history of VTE or STP associated with the largest risk (odds ratio [OR] 35.7), followed by immobilization (OR 22.3), varicose veins (OR 12.1), inherited thrombophilia (OR 6.1), and obesity (OR 2.7). Mean platelet volume was higher (8.5 vs 7.9 fl, P = 0.003) in STP cases.

Conclusions: A history of VTE or STP, immobilization, varicose veins, inherited thrombophilia, and obesity serve as independent clinical risk factors for STP presenting to hospital.

A 49-year-old woman presented to the emergency department with a 3-day history of altered mental status. The patient’s medical history was unremarkable, and she did not take medications.

Background: The chloride intracellular channel (CLIC) protein family consists of six members in humans. CLICs are unique due to their metamorphic property, displaying both soluble and integral membrane forms. The transmembrane conformation was shown to give rise to ion-channel activity in vitro. In recent years, CLICs were implicated in a growing number of physiological processes in various organ systems and associated with distinct disease states. Indeed, the founding member of the family, CLIC5, was shown to be involved in hereditary deafness and various types of cancer. Nevertheless, the natural interactants and endogenous ligands of CLIC5 have not been discovered yet.

Objectives: To find ligands that affect the biochemical properties and activity of CLIC5. We hypothesized that such ligands could serve as important tools for resolving the long-sought cellular roles of CLICs and may offer novel therapeutic avenues for CLIC-associated conditions.

Methods: Using molecular biology and biochemical methods, CLIC5 was overexpressed in Escherichia coli and purified. Next, a high-throughput differential scanning fluorimetry thermal shift assay (TSA) was established and the interaction of approximately 500 natural compounds was examined.

Results: The TSA-based screening approach developed here allows to evaluate the effect of approximately 100 compounds in parallel within approximately 1 hour. Our proof-of-concept screening yielded 11 potential hits, significantly affecting the thermal stability of CLIC5. By examining the dose-dependence of this effect, we identified a specific interaction of CLIC5 with curcumin.

Conclusions: Using the approach we developed, large libraries of small molecules can be screened efficiently to identify novel CLIC5 interactants. Considering the participation of CLIC5 in various physiological and pathological processes, uncovering ligands that inhibit or activate CLIC5 may provide tools to modulate its activity and possibly to ameliorate CLIC5-related pathologies in the future.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Internal medicine is no doubt one of the main pillars of modern medicine. For years it has been considered to be the basis and foundation of medical education and proper clinical service. During the recent coronavirus disease 2019 (COVID-19) pandemic, internal medicine departments were recognized worldwide, and clearly in Israel, to be the true Corona Warriors that provided medical care to patients as well as support and comfort to families. Around the globe, the public applauded and appreciated the bravery of our medical staff, who without hesitation and under direct personal danger provided the best medical care possible despite the hardships of the time. The high personal price and even the heavy cost of staff member lives lost in offering medical care to the pubic did not stop our quest for ongoing medical research.

Coronavirus disease 2019 (COVID-19) affects different people in different ways. Most infected people develop mild to moderate illness and recover without hospitalization. This case report presents a patient who had difficulty eradicating the corona virus due to being treated with rituximab, which depletes B lymphocytes and therefore disables the production of neutralizing antibodies. The regen-COV-2 antibody cocktail consists of two monoclonal antibodies, casirivimab and imdevimab. This cocktail successfully helped the patient's immune system eradicate the virus without auto specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production. In vitro studies confirm that eradication of the intact the virus. This case report emphases the importance of providing external antiviral antibodies regularly, like the regen-COV-2 antibody cocktail, as post- and even pre- SARS-CoV-2 infection prophylaxis in patients treated with rituximab.

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].

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.

Background: An increased serum glucose level is a common finding among patients admitted to hospital with acute illness, including the intensive care unit (ICU), even without a history of previous diabetes mellitus (DM). Glycated hemoglobin (HbA1c) is not only a diagnostic tool for DM but may also has prognostic value for diabetic and non-diabetic populations.

Objectives: To assess the relationship between HbA1c level on admission and clinical outcome among patients admitted to the ICU due to cardiopulmonary disorders with hyperglycemia.

Methods: Patients consecutively admitted to the ICU due to cardiopulmonary disorders who presented with hyperglycemia at admission were evaluated during a 6-month period. HbA1c and serum glucose levels were tested on admission and during the first 24–48 hours of hospitalization. Patients were divided according to HbA1c and compared in term of demographics. We evaluated the effect of HbA1c levels at admission on the clinical outcomes.

Results: Of patients with cardiopulmonary disorders who presented with hyperglycemia at admission to the ICU, 73 had HbA1c levels ≥ 6%, 92 had HbA1c levels < 6%: 63/165 (38.2%) known as diabetic patients. The 30-day all-cause mortality was higher in the group with high HbA1c levels; 38/73 vs. 32/98 (P = 0.02). Increased length of stay in the ICU and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were associated with HbA1c ≥ 6% (P < 0.022 and P < 0.026), respectively

Conclusions: HbA1c ≥ 6% has an important clinical prognostic value among diabetic and non-diabetic patients with cardiopulmonary disorders and hyperglycemia.

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.

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.

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.