Israel Medical Association Journal

Background: The influence of the coronavirus disease 2019 (COVID-19) pandemic caused countries worldwide to implement lockdowns. Elective surgeries were temporarily suspended, with surgeries being performed only for emergent/urgent medical conditions such as hip fractures where early surgical intervention has shown decreased rates of morbidity/mortality.

Objectives: To assess the indirect influence of the COVID-19 pandemic and associated lockdown on hip fracture patients, considering factors such as time to surgery, early postoperative complications, and ambulation status.

Methods: A comparative retrospective study was conducted on consecutive patients presenting to our emergency department (ED) with hip fractures that were treated surgically (N=29) during a 1-month period during the government lockdown due to the COVID-19 pandemic. The treatments were compared to consecutive patients who presented with hip fractures and were treated surgically (N=44) during the same timeframe in the previous year (control). Comparisons were made using t-test, ANOVA test, Fisher's exact test, and chi-square test.

Results: The COVID-19 group was operated on sooner (20.34 vs. 34.87 hours), had fewer early postoperative complications (10.3% vs. 31.8%), had better ambulatory status at discharge, and experienced a shorter hospital stay (5.93 vs. 8.13 days) with more patients being discharged home (72.4% vs. 22.7%).

Conclusions: Patients presenting with hip fractures to our ED during the COVID-19 pandemic lockdown indirectly benefited from this situation by undergoing earlier surgical treatment, thus experiencing fewer early postoperative complications, faster ambulation, and sooner discharge.

Background: Patients with autoimmune disease (AID) and coronavirus disease 2019 (COVID-19) could have higher mortality due to the co-morbidity and the use of immunosuppressive therapy.

Objectives: To analyze the risk factors and outcomes of patients with AID and COVID-19 versus a control group.

Methods: A prospective cohort study included patients with and without AID and COVID-19. Patients were paired by age and sex. Clinical, biochemical, immunological treatments, and outcomes (days of hospital stay, invasive mechanical ventilation [IMV], oxygen at discharge, and death) were collected.

Results: We included 226 COVID-19 patients: 113 with AID (51.15 ± 14.3 years) and 113 controls (53.45 ± 13.3 years). The most frequent AIDs were Rheumatoid arthritis (26.5%), systemic lupus erythematosus (21%), and systemic sclerosis (14%). AID patients had lower lactate dehydrogenas, C-reactive protein, fibrinogen, IMV (P = 0.027), and oxygen levels at discharge (P ≤ 0.0001) and lower death rates (P ≤ 0.0001). Oxygen saturation (SaO₂) ≤ 88% at hospitalization provided risk for IMV (RR [relative risk] 3.83, 95% confidence interval [95%CI] 1.1–13.6, P = 0.038). Higher creatinine and LDH levels were associated with death in the AID group. SaO₂ ≤ 88% and CO-RADS ≥ 4 were risk factors for in-hospital mortality (RR 4.90, 95%CI 1.8–13.0, P = 0.001 and RR 7.60, 95%CI 1.4–39.7, P = 0.016, respectively). Anticoagulant therapy was protective (RR 0.36, 95%CI 0.1–0.9, P = 0.041)

Conclusions: Patients with AID had better outcomes with COVID-19 than controls. Anticoagulation was associated with a lower death in patients with AID.

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: Secondary immune thrombocytopenic purpura (ITP) associated with coronavirus disease 2019 (COVID-19) is a rare but serious complication of the pandemic. Diagnostic criteria include clinical and laboratory findings. Early treatment is often effective, but rare severe bleeding and death can occur. An autoimmune mechanism is likely.

Objectives: To determine a role for molecular mimicry in producing disease.

Methods: Hexapeptide and heptapeptide matches between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and platelet N-glycosylated proteins and other human proteins were assessed.

Results: Shared viral and platelet glycoprotein peptides were found. Copy frequency of these peptides in the human proteome was low for many of the candidate molecular mimics.

Conclusions: The data support a contribution of molecular mimicry in COVID-19 ITP autoimmunity and offer avenues for in vitro diagnostic assay development. The continuation of the pandemic necessitates additional understanding of COVID-19 ITP as well as studies on diagnosis and mitigation.

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in repeated surges of patients, sometimes challenging triage protocols and appropriate control of patient flow. Available models, such as the National Early Warning Score (NEWS), have shown significant limitations. Still, they are used by some centers to triage COVID-19 patients due to the lack of better tools.

Objectives: To establish a practical and automated triage tool based on readily available clinical data to rapidly determine a distinction between patients who are prone to respiratory failure.

Methods: The electronic medical records of COVID-19 patients admitted to the Sheba Medical Center March–April 2020 were analyzed. Population data extraction and exploration were conducted using a MDClone (Israel) big data platform. Patients were divided into three groups: non-intubated, intubated within 24 hours, and intubated after 24 hours. The NEWS and our model where applied to all three groups and a best fit prediction model for the prediction of respiratory failure was established.

Results: The cohort included 385 patients, 42 of whom were eventually intubated, 15 within 24 hours or less. The NEWS score was significantly lower for the non-intubated patients compared to the two other groups. Our improved model, which included NEWS elements combined with other clinical data elements, showed significantly better performance. The model's receiver operating characteristic curve had area under curve (AUC) of 0.92 with of sensitivity 0.81, specificity 0.89, and negative predictive value (NPV) 98.4% compared to AUC of 0.63 with NEWS. As patients deteriorate and require further support with supplemental O₂, the need for re-triage emerges. Our model was able to identify those patients on supplementary O₂ prone to respiratory failure with an AUC of 0.86 sensitivity 0.95, and specificity 0.7 NPV 98.9%, whereas NEWS had an AUC of 0.76. For both groups positive predictive value was approximately 35%.

Conclusions: Our model, based on readily available and simple clinical parameters, showed an excellent ability to predict negative outcome among patients with COVID-19 and therefore might be used as an initial screening tool for patient triage in emergency departments and other COVID-19 specific areas of the hospital.

Heart rate disorders and in particular sinus arrhythmias are known to accompany viral infections. Sinus tachycardia is prevalent in the presence of increased body temperature and respiratory rate. However, bradycardia has also been described for centuries to complicate viral illnesses

Background: Guidelines for pandemic preparedness emphasize the role of sentinel and syndromic surveillance in monitoring pandemic spread.

Objectives: To examine advantages and obstacles of utilizing a sentinel influenza surveillance system to monitor community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity based on Israel's experience from mid-March to mid-May 2020.

Methods: Several modifications were applied to the influenza surveillance system. The clinical component relied mainly on pneumonia and upper respiratory infection (URI) consultations with primary care physicians as well as visits to emergency departments (ED) due to pneumonia. The virological data were based on nasopharyngeal swabs obtained from symptomatic patients who visited outpatient clinics.

Results: By week 12 of the pandemic, the crude and age-specific primary physician consultation rates due to URI and pneumonia declined below the expected level, reaching nadir that lasted from week 15 until week 20. Similarly, ED visits due to pneumonia were significantly lower than expected from weeks 14 and 15 to week 20. The virological surveillance started on week 13 with 6/253 of the swabs (2.3%) positive for SARS-CoV-2. There was a peak of 13/225 positive swabs on week 145.8%. During weeks 17–20, none of the swabs (47–97 per week) were positive for SARS-CoV-2. This trend was similar to national data.

Conclusions: The virological component of the surveillance system showed the SARS-CoV-2 community spread, but had low sensitivity when virus activity was low. The clinical component, however, had no yield. Sentinel surveillance can assist in monitoring future novel pandemics and should be augmented in revised preparedness plans.

Background: Solid organ transplant recipients (SOTRs) are at increased risk for both skin and internal malignancies (IM). The risk of IM after the occurrence of non-melanoma skin cancer (NMSC) has been studied in the general population but very little is known about this association in SOTRs.

Objectives: To evaluate the risk of IM following a prior diagnosis of post transplantation NMSC in SOTRs.

Methods: This single center retrospective cohort study included a study population of 329 SOTRs from Rabin Medical Center who had a post-transplant diagnosis of skin malignancy, internal malignancy, or both from 2012 to 2018.

Results: In total, 135 (41.03%) SOTRs were diagnosed with IM without a preceding diagnosis of NMSC while only 42 (12.76%) patients diagnosed with IM had a preceding diagnosis of NMSC. SOTRs with a diagnosis of NMSC showed a significantly decreased risk of developing subsequent IM (hazard ratio [HR] 0.64, 95% confidence interval [95%CI] 0.44–0.94, P = 0.02) compared to those without a prior NMSC diagnosis. Liver and lung transplant patients showed a significantly decreased risk of developing subsequent IM after a diagnosis of NMSC (HR 0.09 and 0.43, respectively). When stratified by type of IM, only patients who were diagnosed with a hematological malignancy had a significantly lower risk of developing this malignancy if they had a prior NMSC (HR 0.26).

Conclusions: The findings of this study suggest a protective effect of NMSC on subsequent IM in the organ transplant population.

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: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value.

Objectives: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients.

Methods: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality.

Results: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09–1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure.

Conclusion: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of nosocomial infections. Active surveillance for CRAB carriage to identify and isolate colonized patients is used to reduce transmission.

Objectives: To assess the rate and risks of clinical infection among CRAB-carrier and non-carrier patients.

Methods: Hospitalized patients from whom CRAB screening-cultures were obtained between January and June 2018 were identified retrospectively. All CRAB-carriers were compared to a convenient sample of non-carriers and were followed to detect development of CRAB clinical infection during admission.

Results: We compared 115 CRAB carriers to 166 non-carriers. The median age in the study group was 76 years (IQR 71–87) vs. 65 years (55–79) in the non-carriers group (P < 0.001). Residence in a nursing facility, debilitated state, and admission to medical wards vs. intensive care units were more frequent among CRAB-carriers (P < 0.001). Mechanically ventilated patients included 51 CRAB carriers (44%) and 102 non-carriers (61%). Clinical infection developed in 49 patients (17%), primarily CRAB pneumonia. Of the CRAB-carriers and non-carriers, 26/115 (23%) and 23/166 (14%), respectively, developed a clinical infection (P = 0.05). One-third of the ventilated patients were infected. Debilitated state and antibiotic treatment during hospitalization were linked to higher infection rates (P = 0.01). Adjusted analysis showed that mechanical ventilation and CRAB colonization were strongly associated with clinical infection (P < 0.05).

Conclusion: The rate of CRAB infection among carriers was high. Mechanical ventilation and CRAB colonization were associated with CRAB clinical infection, primarily pneumonia

Background: It is important to predict acute cholecystitis (AC) before a laparoscopic cholecystectomy because inflammation of the gallbladder predicts the need for open conversion and subsequent morbidity after a laparoscopic cholecystectomy.

Objectives: To create an index based on clinical, laboratory, and ultrasound criteria on admission that will predict AC on pathological examination in patients presenting acutely.

Methods: We retrospectively reviewed consecutive cases of emergency laparoscopic cholecystectomies conducted by three experienced surgeons between 1 October 2014 and 31 January 2018. Independent variables were age, sex, presenting symptoms, admission laboratory tests, and ultrasound findings. The outcome variable was AC on histological examination. An index was created from all variables that added significantly to the logistic regression analysis.

Results: Eight variables that contributed significantly to the model, included age, male sex, vomiting on admission, an increased proportion of neutrophils, a normal aspartate aminotransferase test, a normal serum amylase test result, a thick gall bladder wall, and pericholecystic fluid. An index of ≤ 2 to ≥ 8 created from those variables had a graded risk for AC of 1.8% to 92.0% with a c-statistic of 0.86 (95% confidence interval 0.81–0.91). Operating time and bleeding increased in those with a higher index.

Conclusions: An index including age, sex, symptoms, and selected laboratory results as well as ultrasound characteristics had an excellent graded risk in the prediction of histological AC that was associated with operating time and an increased risk of bleeding during the operation.

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.

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

Zinc is a trace element, which is abundant in nature. It is also an essential and important micronutrient found in many foods. It has a role in multiple bodily processes including wound healing and boosting of the immune system. This review shows evidence of zinc deficiency in cancer patients of all types, a deficiency that correlates with disease severity and negatively correlates with survival rates. Lower zinc levels led to more severe and advanced disease symptoms and to lower survival rates. Zinc is a nanoparticle and acts as a photosensitizer in photodynamic therapy in various combinations with other substances. It also shows incredible cytotxicity and tumor suppressive ability in studies conducted both in vitro and in vivo as well as in studies conducted in humans. This result is shown in all types of cancer tested. Zinc shows incredible toxicity toward cancer cells without showing any side effects toward healthy cells. It is recommended that zinc be added to cancer treatment regimens to alleviate zinc deficiency in cancer patients and perhaps to treat cancer as a whole