Israel Medical Association Journal

Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response.

Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry

Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts.

Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5–57) months.

Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Background: Diabetes mellitus (DM) is one of the risk factors for progression from latent to active tuberculosis. However, the effect of DM on subsequent tuberculosis treatment is still inconclusive.

Objectives: To compare tuberculosis treatment outcomes and the rate of drug resistance of tuberculosis patients with or without DM.

Methods: This case-control study was conducted between 2005 and 2015 at the only tuberculosis ward in Israel. All 80 tuberculosis patients who had DM and were hospitalized during the study period were included in this study, as were a randomized sample of 213 tuberculosis patients without DM. Demographic, clinical, and laboratory data were collected from patient files in the hospital and clinics after discharge.

Results: Tuberculosis patients with DM were more often older and more likely to be Israeli citizens with a lower socioeconomic status than patients without DM. No statistically significant differences were found in clinical presentation, radiological findings, and sputum smear tests between the two groups. Culture converting times were prolonged in patients with DM compared to normoglycemic patients. Multidrug drug resistance tuberculosis was more common among normoglycemic tuberculosis patients than tuberculosis patients with DM (9.2% vs. 1.6%, P = 0.12). Treatment success rates were 76.2% and 83.1% for tuberculosis patients with or without DM, respectively (P = 0.18). DM was not statistically significant in the multivariate analysis predicting treatment success, which controlled for age, citizenship, compliance, addictions, and chronic diseases.

Conclusions: The presence of DM does not necessarily affect tuberculosis treatment outcomes as long as treatment compliance is optimal.

Background: Laparoscopic removal of ovarian dermoid cysts has been associated with increased risk for recurrence.

Objectives: To investigate the risk factors associated with recurrence of dermoid cysts.

Methods: We conducted a retrospective review of all women who underwent cystectomy for ovarian dermoid cysts by laparoscopy or laparotomy. At discharge, patients were instructed to undergo a yearly ultrasound exam. A follow-up telephone call was conducted to assess whether an additional surgery for dermoid cysts was required and whether ultrasound recurrence of dermoid cysts was suspected.

Results: The study cohort included 102 participants (92 [90.2%] operated by laparoscopy and 10 [9.8%] by laparotomy). The mean follow-up from the index surgery to the interview was 72.1 ± 38.2 months. The rates of recurrent surgery were similar among women who underwent laparoscopic cystectomy compared with laparotomy (5/92 [5.4%] vs. 1/10 [10.0%], respectively; P = 0.5), while the rates of reported ultrasound recurrence were significantly lower in the laparoscopy group compared with the laparotomy group (10/102 [10.9%] vs. 4/10 [40.0%], respectively; P = 0.03). Additional factors including age, cyst diameter, diagnosis of torsion, intraoperative cyst spillage, estimated blood loss, intraperitoneal adhesions, and postoperative fever were not associated with recurrence.

Conclusions: Ultrasound recurrence of dermoid cysts is not uncommon and could be associated with the surgical approach.

Background: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty.

Objectives: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel.

Methods: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected.

Results: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/10⁶ inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m² .Obesity, with a BMI ≥ of 30 kg/m², was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%).

Conclusions: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

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: Over the past several years there has been a marked increase in the number of Israel Defense Forces (IDF) soldiers having hip arthroscopy based on magnetic resonance arthrography diagnosis of hip labral tears and/or impingement.

Objectives: To detail characteristics of soldiers who underwent hip arthroscopy and assess outcomes and rate of return to duty.

Methods: A retrospective chart review was conducted of all soldiers who underwent hip arthroscopy 2018 to 2020, and soldiers referred for hip arthroscopy during 2021. Demographic, medical, and military service data were collected from the computerized patient record.

Results: Our study comprised 117 soldiers (29% combatants, 24% females) who underwent hip arthroscopy, mean age 22 ± 3 years, range 18–42; 45% had physiotherapy before surgery; 31% were diagnosed during or within 3 months of having back pain and 20% had been referred for psychological assistance (not related to the hip pain); 15.4% had serious adverse events. The mean time to return to any duty (including clerical work) was 8.0 ± 0.6 months; 56% of the soldiers never returned to service and were discharged from the military. During the one-year follow-up, only 6% returned to their full pre-symptom activity.

Conclusions: The short-term results of IDF soldiers who underwent hip arthroscopy during the study period were much inferior to those reported among athletes. The lack of specificity of the diagnostic tools (history, examination, and imaging) used to determine whether surgery for hip pain is likely to be beneficial in this population may be contributing to over-diagnosis and over-treatment.

Overuse of healthcare services is a common phenomenon defined as: “a healthcare service that is provided under circumstances in which its potential for harm exceeds the possible benefit.” It is expressed in the gap between desired services and available ones and is accompanied by high financial and human life costs. One-fifth to one-third of patients receives unnecessary, ineffective, or potentially harmful treatments or services. One of the greatest challenges to understanding overuse is the lack of definition for appropriate use. Apart from the physical and mental damage caused by overuse or improper use of medical services, this phenomenon has many implications, such as increasing waiting times for services, creating long queues, and incurring considerable financial costs as over 10% of hospital expenses are used to correct medical errors or preventable infections. Government intervention through economic arrangements such as deductibles and pre-authorization of services by the insurer are partially effective in reducing the overuse of health services. Additional solutions include ensuring safety and quality of care as well as shared decision-making.

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: 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 coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on healthcare systems worldwide. The fear of seeking medical attention to avoid the possibility of being infected may have altered the course of some diseases.

Objectives: To describe our experience with the management of patients with acute cholecystitis during the pandemic at our medical center.

Methods: We compared patients treated for acute cholecystitis between 1 March and 31 August 2020 (Group I) to patients admitted with the same diagnosis during the same months in 2019 (Group II). We evaluated demographics, presenting symptoms, laboratory and imaging findings at presentation, the disease's clinical course, management, and outcome.

Results: Group I consisted of 101 patients and group II included 94 patients. No differences were noted for age (66 years, IQR 48–78 vs. 66 years, IQR 47–76; P = 0.50) and sex (57.4% vs. 51.1% females; P = 0.39) between the two groups. The delay between symptom onset and hospital admission was longer for Group I patients (3 days, IQR 2–7 vs. 2 days, IQR 1–3; P = 0.002). Moderate to severe disease was more commonly encountered in Group I (59.4% vs. 37.2%, P = 0.003). Group I patients more often failed conservative management (36% vs. 6%, P = 0.001) and had a higher conversion rate to open surgery (15.4% vs. 0%, P = 0.025).

Conclusions: Patients presenting with acute cholecystitis during the COVID-19 pandemic more often presented late to the emergency department and more showed adverse outcomes

Background: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results.

Objectives: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2).

Methods: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression.

Results: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29–0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27–0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16–0.95) were analyzed separately.

Conclusions: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

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: 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

Cardiac tumors are rare and the majority are from a primary source outside of the heart. Most are found, incidentally, with echocardiography but often additional cardiac imaging is needed to refine the differential diagnosis. For this purpose, cardiac magnetic resonance imaging (MRI) and to a lesser extent cardiac computed tomography (CT) or ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (¹⁸F-FDG PET/CT) are useful imaging modalities to better characterize a cardiac tumor and determine the likelihood of a neoplastic versus non-neoplastic origin. Cardiac CT may be useful to evaluate the effect of treatment while using ¹⁸F-FDG PET/CT to evaluate cardiac masses is under-studied but may be useful in patients who are already having a scan performed for oncologic reasons. It is through understanding the clinical context of a newly discovered cardiac mass, knowledge of the typical locations of various cardiac tumor types, combined with imaging techniques that avoid ionizing radiation that yield the greatest confidence in the noninvasive diagnosis of a cardiac mass