Israel Medical Association Journal

Background: High prevalence of hepatitis C (HCV) among people with severe mental illness (SMI) is attributed mostly to current or past intravenous (IV) drug use. However, such history may disappear from patient files over time, especially in chronic SMI with prolonged psychiatric admissions.

Objectives: To explore HCV and SMI cross-morbidity (HCV/SMI) in a hospitalized population.

Methods: In this observational, retrospective, historical computerized study we examined prevalence, characteristics, and outcomes of patients with HCV/SMI compared to HCV alone in patients admitted to an Israeli hospital 1 January 2005 to 31 December 2020.

Results: Of 1638 eligible HCV patients, 219 (13.4%) were HCV/SMI. Significantly more native Israelis showed HCV/SMI than HCV alone (36.1% vs. 18.1%, P = 0.013) and history of IV drug use (60.3% vs. 32.4%, P < 0.001). Among Israeli natives, more Jews were SMI/HCV compared to HCV only (67.1% vs. 45%, P < 0.01). Among non-native Israelis, immigration age was lower in SMI/HCV compared to HCV only (27.97 vs. 37.23 years, P < 0.001). No differences were found in mortality or cirrhosis, although HCV/SMI patients experienced earlier mortality compared to HCV alone (61.42 ± 14.3 vs. 72.8 ± 14.6 years, P < 0.001). Cirrhosis among HCV/SMI patients was a risk factor for early mortality (hazard ratio 5.528, 95% confidence interval 3.721–8.213).

Conclusions: HCV/SMI is related to early mortality, particularly with cirrhosis. There is significantly high SMI prevalence in hospitalized HCV patients, representing a unique at-risk population. Identification during hospitalization and medical recommendations at discharge may fill the gaps.

Background: BRCA1/BRCA2 female pathogenic sequence variant (PSV) carriers in Israel are offered semiannual cancer antigen 125 (CA125) serum level determination and transvaginal ultrasound until performing risk reducing salpingo-oophorectomy (RRSO), even with the lack of proven efficacy of these procedures in providing adequate early detection of ovarian cancer.

Objectives: To report the results of longitudinal CA125 measurements in BRCA1/BRCA2 carriers as a tool for ovarian cancer detection in a single medical center in Israel.

Methods: Asymptomatic BRCA1/BRCA2 PSV carriers attending the Meirav High Risk Clinic at Sheba Medical Center for more than 3 years were eligible. Data on specific PSV, risk reducing surgeries, and cancer diagnoses were obtained from participant records. We used chi-square and Wilcoxon-Rank tests for statistical analyses.

Results: Overall, 739 (399 BRCA1, 336 BRCA2, 4 BRCA1 + BRCA2) PSV carriers were included. Mean age at the start of follow-up was 38.96 ± 11.13 years, mean follow-up time was 7.93 ± 2.34 years, (5860.80 women/years). Most participants (490/739 [66.3%]) had stable CA125 levels (± 5 U/µl). Of participants, 61 had CA125 levels > 35 U/µl at least twice (n=42) or at least doubling of marker levels to a minimum of 20 U/µl (n=19), results that have led to further cancer defining investigations. Of these, 14 and 4 were diagnosed with breast and ovarian cancer, respectively.

Conclusions: Longitudinally stable CA125 levels were noted in most BRCA1/BRCA2 PSV carriers and elevated levels were a poor marker for ovarian cancer development.

Background: Several studies have shown an association between increased red blood cell distribution width (RDW) and adverse outcomes in various acute diseases. Small studies have suggested that RDW is a useful predictor of acute pancreatitis severity.

Objectives: To determine the association between RDW at admission and early mortality in acute pancreatitis. To assess whether RDW adds to the predictive ability of the Glasgow Imrie Score.

Methods: In this observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Patients were divided into two groups according to RDW: normal RDW (RDW ≤ 14.5%) and elevated RDW (RDW > 14.5%).

Results: Within 30 days of admission, 29/438 patients (6.6%) with increased RDW and 20/1250 patients (1.6%) with normal RDW had died: univariate analysis (odds ratio 4.6, 95% confidence interval 2.45–7.9, P < 0.001), fully adjusted model (odds ratio 3.29, 95% confidence interval 1.75–6.26, P < 0.001). We calculated receiver operating characteristic curve (ROC) for RDW alone, Glasgow Imrie Score alone, and a combination of Glasgow Imrie Score with RDW. We assessed their ability to predict 30-day mortality. Area under the ROC curve (AUC) of RDW alone was 0.671 and Glasgow Imrie Score AUC was 0.682; Glasgow Imrie Score plus RDW had an AUC of 0.769.

Conclusions: In patients with acute pancreatitis, elevated RDW at admission was independently associated with increased 30-day mortality. The addition of RDW to a pancreatitis prognostic tool such as the Glasgow Imrie Score improves its predictive ability.

Background: One of the major causes of reversible visual impairment is a refractive error, which can be corrected through refractive surgery. Data regarding the outcomes and complications of these procedures exist; however, there is a notable gap in understanding the factors leading to patient rejection, particularly in diverse populations like Israel.

Objectives: To detect clinical risk factors of patients who intend to undergo LASIK procedure and to improve the conversion rates of LASIK procedure in this population.

Methods: The study included a retrospective analysis of patients who were rejected from having refractive surgery in two Enaim Refractive Surgery Centers: Jerusalem and Tel Aviv. Comparisons between centers were conducted using the t-test for continuous variables and Fisher's exact test for categorical data.

Results: Our study included 337 patients who were rejected from having refractive surgery, including 152 (45.1%) who were rejected permanently and 185 (54.9%) rejected temporarily. The most common reasons for permanent rejection were corneal irregularity (n=81, 53.3%), keratoconus (n=27, 17.8%), thin corneas (n=13, 8.6%), and amblyopia (n=10, 6.6%). The most common temporary reasons were unstable refraction (n=96, 51.9%), prolonged use of contact lenses (n=54, 29.2%), and corneal irregularity (n=16, 8.6%).

Conclusions: The leading permanent cause of rejection for refractive surgery was a corneal irregularity, whereas the primary temporary cause was unstable refraction. In a time of rapid technological advancements and growing demand for freedom from glasses, there is an increasing need for more informed and patient-focused refractive correction approaches.

Colorectal cancer (CRC) is a major health concern, ranking as the third most common cancer in the United States. Screening programs, especially colonoscopy, play a crucial role in preventing CRC by removing and detecting polyps or early-stage cancers. Despite inherent risks, colonoscopy's effectiveness in saving lives is significant. In this review, we analyzed the outcomes of screening colonoscopies in an asymptomatic population for 15 years, focusing on detection rates and complications. We compared the data with previous meta-analyzes to evaluate changes in efficacy and safety. We conducted a systematic search of medical literature databases (1 January 2012 to 31 December 2023) for English-language studies on CRC screening colonoscopy. Our inclusion criteria comprised complete articles with over 500 participants with extractable data and a focus on screening colonoscopy outcomes in average-risk populations. In total, 2,897,025 people were screened, most (99.6%) were asymptomatic and were an average-risk population. Colonoscopy was complete and reached the cecum in 97–99% of the procedures. CRC was found in 0.5% (95% confidence interval [95%CI] 0.4–0.7%) of the participants. Advanced adenoma was found in 7.6% (95%CI 6.2–9.3%) of the cases. Complications were rare. Perforation developed in 0.022% of the cases and bleeding in 0.148%. Our findings exhibited a significant increase in the detection yield of adenomas and advanced adenomas with low complication rates, which shows that colonoscopy is feasible and suitable for screening for CRC in asymptomatic people.

Background: Cesarean deliveries (CD) are commonly performed using neuraxial anesthesia. The use of neuraxial morphine has proven beneficial in terms of postoperative pain management; however, its effect on postoperative urine retention remains unclear.

Objectives: To determine whether morphine injection into the neuraxis during CD influences postoperative urinary retention rate.

Methods: We conducted a retrospective case-control observational study of patients undergoing CD. We compared patients using morphine injected into the intrathecal or epidural spaces (November 2020 to October 2021) to a historical cohort of patients undergoing CD without morphine (November 2019 to October 2020). The primary outcome was the rate of postoperative overt urinary retention necessitating bladder catheterization.

Results: The study group comprised 283 patients, and 313 patients in the control group were eligible for analysis. No differences were found with respect to the baseline demographic and indication for CD. The number of postpartum urinary bladder catheterizations due to urine retention was higher in the study group (5% vs. 1%, P-value = 0.003). No cases of 30-day readmission were recorded. Moreover, patients treated with neuraxial morphine required fewer repeat doses of postoperative anesthesia (oral analgesia 7.4 vs. 10.1, intravenous analgesia 0.29 vs. 0.31, oral opioids 0.06 vs. 3.70, intravenous opioids 0.01 vs. 0.45, P-value < 0.001 for all)

Conclusions: While neuraxial morphine used during CD appears to be safe and effective, the risk of postoperative urinary retention seems to be increased due to its use. Cases of overt urinary retention treated by bladder catheterization does not lead to short-term complications.

Background: Perianal abscess is a common condition among adults. The treatment of choice includes early and efficient drainage. The data regarding risk factors for abscess recurrence, fistula formation, and complications are limited as recent publications mainly focus on patients with inflammatory bowel disease.

Objectives: To determine risk factors for abscess recurrence and fistula formation with regard to patient and surgical characteristics.

Methods: A retrospective analysis was performed on patients who presented to the emergency department and were diagnosed with perianal abscess between 2011–2020.

Results: We included 983 consecutive patients; 741 men, average age 43 years. Recurrence was documented in 434 cases. Crohn’s disease was reported in 70, of which 50 had recurrent episodes (P < 0.0001); 121 of the 234 patients who smoked had recurrence (P = 0.0078); 8% had short symptomatic period (< 24 hours), which was a predisposing factor for recurrence, P < 0.0001. Patients in the non-recurrent group waited 2.53 hours less for surgical intervention (P < 0.0005(. The average time for recurrent episode was 18.95 ± 33.7 months. Fistula was diagnosed in 16.9% of all cases, while 11.6% were within the recurrent group. Surgical expertise of the physician did not significantly change the recurrence rate.

Conclusions: Crohn’s disease and smoking were the only significant risk factors for recurrence of perianal abscess. Timely intervention and drainage of sepsis should not be delayed. Involvement of more experienced surgeons did not seem to alter the natural history of the disease.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism and manifests as a multisystem disease. Most patients present with oropharyngeal malformations, cardiomyopathies, elevated liver enzymes, and hypoglycemia. Treatment with D-galactose has been shown to improve symptoms. Our patient presented with PGM1 deficiency. She conceived spontaneously. Throughout her pregnancies, our patient was monitored by a multidisciplinary team of cardiologists, endocrinologists, and physicians with experience in high-risk pregnancy. She delivered twice by cesarean section. Our case highlights the importance of a multidisciplinary approach and individualized management of prenatal and postpartum care of a patient with a PGM1 deficiency. To the best of our knowledge, there have been no reports about a PGM1-deficient patient who conceived and delivered.

Background: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

Objectives: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS.

Methods: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls.

Results: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels.

Conclusions: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Background: Several studies have shown that patients with fibromyalgia present with neuroendocrine, inflammatory, and coagulation features linked to cardiovascular disease development. However, the exact profile of cardiovascular risk factors and events in fibromyalgia remains to be defined.

Objectives: To compare the profile of cardiovascular risk factors and events between fibromyalgia outpatients and the general population in Italy.

Methods: Cardiovascular risk factors and events in fibromyalgia females were collected using the criteria adopted in the CUORE Project.

Results: The study comprised 62 female fibromyalgia patients and 4093 female controls from 35 to 75 years of age. The prevalence of hypertension, diabetes, atrial fibrillation, transient ischemic attack, and cardiovascular total burden was significantly higher in fibromyalgia females than in the general Italian population. No difference was found in blood fasting glucose, triglycerides, total and fractionated cholesterol levels, body mass index, and metabolic syndrome (MetS). The MetS rate was underestimated for methodological aspects.

Conclusions: Fibromyalgia is associated with an increased cardiovascular burden, probably through a specific risk factor profile.

Fibromyalgia syndrome is a chronic widespread musculoskeletal pain syndrome primarily characterized by fatigue, sleep disturbances, and cognitive impairment. Its etiology remains elusive despite ongoing research and has multifactorial elements. It has been shown that traumatic events and neuro-inflammation, autoimmunity, and genetic factors contribute to the pathogenesis of fibromyalgia syndrome.

Recent evidence has pointed to a bi-directional link between cardiovascular disease, traditional cardiovascular risk factors, and metabolic syndrome (MetS), together with the presence of fibromyalgia [1].

Background: Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained.

Objectives: To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study.

Methods: A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI).

Results: Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7–9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001).

Conclusions: Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.

Background: In Israel, breast cancer prevalence is lower among Arab than Jewish women, but incidence is increasing among Arab women at a younger age.

Objectives: To explore differences between Arab and Jewish women with breast cancer with respect to age at diagnosis, associated risk factors, and use of hormonal medications.

Methods: We conducted a retrospective database study comparing Arab and Jewish women with breast cancer focusing on age at diagnosis, smoking history, obesity, and previous hormonal medication usage, including oral combined contraceptive pills (OCCP), progestogens, hormonal medications for treatment of infertility, and hormone replacement therapy (HRT).

Results: The study included 2494 women who were diagnosed with breast cancer during 2004–2015. Age at diagnosis was lower among Arab women (50.7 ± 13.1 years vs. 55.4 ± 12.6 years, P < 0.0001). The rate of smoking was higher among Jewish women (16.0% vs. 4.3%, P < 0.0001). The rate of obesity was higher in Arab women older than 50 years at diagnosis (59.0% vs. 42.4%, P < 0.0001). Arab women demonstrated a lower overall chance of previous use of all types of hormonal medications (odds ratio [OR] 0.6, 95% confidence interval [95%CI] 0.6–0.8) compared to Jewish women. Arab women were more likely to have used progestogens (OR 1.7, 95%CI 1.4–2.2) and medications for treatment of infertility (OR 2.3, 95%CI 1.5–3.4) and less likely OCCP (OR 0.4, 95%CI 0.3–0.6) and HRT (OR 0.4, 95%CI 0.3–0.5).

Conclusions: Previous use of hormonal medications may contribute to incidence of breast cancer in Arab women.

Background: The evaluation of syncope in emergency departments (EDs) and during hospitalization can be ineffective. The European Society of Cardiology (ESC) guidelines were established to perform the evaluation based on risk stratification.

Objectives: To investigate whether the initial screening of syncope adheres to the recent ESC guidelines.

Methods: Patients with syncope who were evaluated in our ED were included in the study and retrospectively classified based on whether they were treated according to ESC guidelines. Patients were divided into two groups according to the ESC guideline risk profile: high risk or low risk.

Results: The study included 114 patients (age 50.6 ± 21.9 years, 43% females); 74 (64.9%) had neurally mediated syncope, 11 (9.65%) had cardiac syncope, and 29 (25.45%) had an unknown cause. The low-risk group included 70 patients (61.4%), and the high-risk group included 44 (38.6%). Only 48 patients (42.1%) were evaluated according to the ESC guidelines. In fact, 22 (36.7%) of 60 hospitalizations and 41 (53.2%) of 77 head computed tomography (CT) scans were not mandatory according to guidelines. The rate of unnecessary CT scans (67.3% vs. 28.6%, respectively, P = 0.001) and unnecessary hospitalization (66.7% vs. 6.7%, respectively, P < 0.02) were higher among low-risk patients than high-risk patients. Overall, a higher percentage of high-risk patients were treated according to guidelines compared to low-risk patients (68.2% vs. 25.7% respectively, P < 0.0001).

Conclusions: Most syncope patients, particularly those with a low-risk profile, were not evaluated in accordance with the ESC guidelines.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders. Acute cholangitis (AC) is a life-threatening illness.

Objective: To determine whether NAFLD is a risk factor for the severity of AC.

Methods: We retrospectively studied hospitalized patients with a diagnosis of AC over 5 years. Patients were divided into a NAFLD group and a non-NAFLD group. We compared the two groups with regard to demographic characteristics, co-morbidities, laboratory data, and severity of AC (including Charlson Comorbidity Index [CCI] and Tokyo Consensus meeting criteria).

Results: In all, 298 of 419 hospitalized patients diagnosed with AC met the inclusion criteria. Of these, 73/298 (24.5%) were in the NAFLD group. NAFLD group patients were younger and more likely to be diabetic and obese than the non-NAFLD group. Participants in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (P < 0.05, for each parameter) and with more events of organ dysfunction (P < 0.001) and bacteremia (P < 0.005). Regarding the severity of AC according to Tokyo Consensus, among the NAFLD group more patients presented with Grade II (39.7 vs. 33.3%, P < 0.001) and Grade III (23.3 vs. 18.3, P < 0.001) cholangitis. More Grade I cholangitis was found among the non-NAFLD group (48.4 vs. 37%, P < 0.001). Multivariate logistic regression analysis showed that NAFLD was independently associated with severe AC, Grade III (odds ratio 3.25, 95% confidence interval 1.65–6.45, P = 0.038).

Conclusions: NAFLD is an independent risk factor for the severity of AC.