Israel Medical Association Journal

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.

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

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.

Background: Some studies have shown that patients who are hospitalized with severe COVID-19 also have low levels of vitamin D. It is known that vitamin D can reduce the risk of infections and down regulate the immune/inflammatory reaction.

Objectives: To investigate the association between vitamin D status and lymphocyte subpopulations in hospitalized pneumonia COVID-19 patients.

Methods: In 33 positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with radiologic evidence of interstitial pneumonia and in 16 healthy control subjects matched for age, sex, and seasonality lymphocyte subpopulations and vitamin D levels were evaluated.

Results: The majority of patients with COVID-19 pneumonia (70.8%) presented vitamin D deficiency. The percentages of neutrophils presented a negative correlation (r = -0.74; P < 0.001), whereas the percentages of lymphocytes presented a positive correlation (r = 0.43; P < 0.01) with 25(OH)D. Moreover, vitamin D levels were positively correlated with CD3+ (r = 0.37, P < 0.05), CD4+ (r = 0.41, P < 0.05), CD8+ (r = 0.32, P < 0.07), and CD19+ (r = 0.38, P < 0.05).

Conclusions: This preliminary study confirms the high prevalence of vitamin D deficiency in patients with COVID-19 pneumonia and that vitamin D deficiency is associated with a reduction of lymphocyte subsets and altered T-lymphocyte activation. This finding may contribute to clarify the mechanisms by which vitamin D influences the course and outcome of COVID-19 pneumonia.

Background: Low serum albumin is known to be associated with mortality in sepsis, as it reflects effects of nutrition, catabolism, and edema.

Objectives: To examine the association of albumin levels with in-hospital mortality in adults with sepsis, stratified by age groups.

Methods: This nationwide retrospective cohort study comprised patients admitted with sepsis to intensive care units in seven tertiary hospitals during 2003–2011. Only patients with available serum albumin levels at hospital admission and one week after were included. Patients with an intra-abdominal source of sepsis were excluded. The association between sepsis and mortality was analyzed using multivariate logistic regression models.

Results: The study included 3967 patients (58.7% male, median age 69 years). Mean serum albumin levels were 3.1 ± 0.7 g/dl at admission and 2.4 ± 0.6 g/dl one week later. In a multivariate logistic regression model, serum albumin one week after admission was inversely associated with in-hospital mortality (odds ratio [OR] 0.64, 95% confidence interval 0.55–0.73 per 1 g/dl). In an age-stratified analysis, the association was stronger with younger age (OR 0.44 for patients aged < 45 years, 0.60 for patients aged 45–65 years, and 0.67 for patients aged > 65 years). Serum albumin on admission was not associated with in-hospital mortality.

Conclusions: The decline in serum albumin one week after admission is a stronger predictor of mortality in younger patients. Older patients might have other reasons for low serum albumin, which reflect chronic co-morbidity rather than acuity of disease.

Background: Lower extremity amputation related to diabetes is a serious outcome, which can have devastating effects on the patient and family. The epidemiology of amputations has recently been used as a possible measure of the adequacy of medical prevention and treatment of diabetes and diabetic foot complications.

Objectives: To report on patients undergoing amputations at one medical center in Israel, their co-morbidities, and the outcomes.

Methods: A retrospective chart study was conducted of amputees operated between 1 September 2017 and 30 September 2018.

Results: The study population comprised 72 patients who had major amputations for diabetes and/or ischemia, mean age 72 ± 10 years, 74% males, 93% with type 2 diabetes. Mean age corrected Charlson Comorbidity Index was 8.2 ± 2.1 with 90% (65 patients) presenting with a score of 6 or higher. Before the recent deterioration, fewer than 20% of the patients exited their home routinely and 24% had an official diagnosis of dementia. There were 31 below knee amputations (BKA) and 41 above knee amputations (AKA). The 30-day, 3-month, 1-year, and 2-year mortality rates were 15.3%, 27.8%, 43.1%, and 54.2% respectively. Median survival period was 20 months. Survival after AKA was 13.4 ± 20, which was significantly less than after BKA (25.4 ± 2.7, P = 0.097).

Conclusions: Factors other than the quality of management of patients with diabetes and complications may contribute to amputation rates; thus, making speculations from international comparisons of raw amputation rates problematic. This population was less healthy than reported in most studies.

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.

Cannabis and cannabinoids have been known for thousands of years for their promising potential as analgesics. Chronic pain is a common complaint among many patients with rheumatic conditions. These disorders have revisited the medical approach toward cannabis and its potential role in pain relief. In addition, in recent years, information has mounted about the immunomodulatory effects of cannabis. In this review we discuss findings on the benefits cannabis may have in rheumatic and autoimmune disorders.

Background: Data on how the coronavirus disease 2019 (COVID-19) affected consultations in ophthalmic departments are sparse.

Objectives: To examine the epidemiology of ophthalmic consultations in a large pediatric emergency medicine department (PED) during the first nationwide COVID-19 lockdown in Israel.

Methods: The database of a tertiary pediatric medical center was retrospectively reviewed for patients aged < 18 years who attended the PED from 17 March to 30 April 2020 (first COVID-19 lockdown) and the corresponding period in 2019. Background, clinical, and disease-related data were collected from the medical charts and compared between groups.

Results: The study included 757 PED visits. There were no significant differences in demographics between the groups. The 2020 period was characterized by a decrease in PED visits (by 52%), increase in arrivals during late afternoon and evening (P = 0.013), decrease in visits of older children (age 5–10 year), and proportional increase in younger children (age 1–5 years) (P = 0.011). The most common diagnoses overall and during each period was trauma followed by conjunctivitis and eyelid inflammation. The mechanisms of trauma differed (P = 0.002), with an increase in sharp trauma and decrease in blunt trauma in 2020 (P < 0.001 for both). In 2020, 95% of traumatic events occurred in the home compared to 54% in 2019 (P < 0.001).

Conclusions: Parents need to learn appropriate preventive and treatment measures to prevent serious and long-term ophthalmic injury while minimizing their exposure to the COVID-19. PEDs and ophthalmic pediatric clinics should consider increasing use of telemedicine and the availability of more senior physicians as consultants during such times.

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: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently used method for obtaining tissue samples for the diagnosis of various respiratory conditions, including lung cancer staging. In most cases, EBUS-TBNA is performed under moderate sedation (MS). However, in cases of respiratory compromised patients, if this procedure is performed, it is conducted under general anesthesia (GA).

Objective: To assess the diagnostic yield of EBUS-TBNA among respiratory compromised patients.

Methods: Data of consecutive patients (n=191) who underwent EBUS-TBNA at our medical center between January 2019 and December 2019 were retrospectively analyzed. Respiratory compromised patients underwent GA and patients without respiratory compromise were mostly moderately sedated (MS). Characteristics, diagnostic yield, and complication rates were compared.

Results: Diagnostic yield was similar between the two sedation modes (89% in GA group and 78% in the MS group, P = 0.11). The number of total samples obtained per procedure was significantly higher in the GA vs. the MS group (4.1 ± 2.1 vs. 2.1 ± 1.33, P < 0.01). The overall complication rate was 13% and 20.9% in the GA vs. the MS groups, respectively (P = 0.14), with the most frequent complication being minor bleeding. Interestingly, while the number of brushings, bronchoalveolar lavage, and endobronchial biopsy were similar, the percent of subjects who underwent transbronchial biopsy was significantly higher in the GA group (49% vs. 24.2%, P < 0.01).

Conclusion: EBUS-TBNA performed under GA among respiratory compromised patients is safe and has similar diagnostic yield to that of patients without a respiratory compromise

Background: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS).

Objectives: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal.

Methods: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy.

Results: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient’s sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women.

Conclusion: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal

Background: The CHA₂DS₂-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF).

Objectives: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA₂DS₂-VASc score in SR.

Methods: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA.

Results: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA₂DS₂-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA₂DS₂-VASc group (45, interquartile ratio [IQR] 36–49) vs. 37 (IQR 28–46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7–9.3) vs. 1.6 (IQR 0.78–5.4), P < 0.001; NLR 2.7 (IQR 2.1–3.8) vs. 2.1 (IQR 1.6–2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups.

Conclusions: Patients in SR with high CHA₂DS₂-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA₂DS₂-VASc score.