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: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

Background: Chest radiograph is a standard procedure for diagnosis of pneumonia; however, interpretation shows considerable variability among observers.

Objectives: To assess the extent of agreement between pediatric residents and board-certified radiologists in interpretation of chest radiography for detection of pneumonia. To evaluate the impact of resident experience, patient age, and signs of infection on this phenomenon.

Methods: The cohort included 935 patients with suspected pneumonia admitted to the pediatric emergency department at a non-tertiary medical center in Israel 2019–2021. All patients had chest radiographs interpreted by a resident and a radiologist. Interobserver agreement was assessed using Κ and prevalence-adjusted bias-adjusted κ (PABAK) with 95% confidence intervals (95%CI). Results were stratified by resident experience (junior or senior), patient age (≤ 3 vs. > 3 years), white blood cells (≤ 15,000 vs. > 15,000 cells/ml), C-reactive protein (≤ 5 vs. > 5.0 mg/dl), and temperature (< 38.0°C vs. ≥ 38.0°C).

Results: Moderate agreement between pediatric residents and radiologists was demonstrated for diagnosis of pneumonia (κ= 0.45). After adjustment for disease prevalence, the extent of agreement increased to near-substantial (PABAK= 0.59, 95% confidence interval 0.54–0.64). The extent of agreement was higher for children over 3 years of age and in patients without clinical or biochemical features of pneumonia, especially when diagnosis of pneumonia was ruled out.

Conclusions: A second reading of chest radiographs by an experienced radiologist should be considered, particularly for patients younger than 3 years of age and in those with signs of infection and an initial diagnosis of pneumonia.

A full-term 1-month-old female was brought to our pediatric emergency department (ED) due to 3 days of increasing respiratory distress. She was born at term to healthy, consanguineous (2nd degree) Bedouin parents after a pregnancy that lacked adequate monitoring. At birth, a physical examination revealed an imperforate anus and a recto-vestibular fistula, left hydronephrosis, large patent ductus arteriosus (PDA), and an atrial septal defect (ASD). The diagnosis of VACTER association was made. Importantly, she had no respiratory difficulties, nor hemivertebra or tethered cord.

On admission to the ED, she presented with severe respiratory distress, tachypnea, dyspnea, and hypoxemia without evidence of upper airway obstruction or stridor. Due to impending respiratory failure, she was transferred to the pediatric intensive care unit and started on non-invasive respiratory support through a high-flow nasal cannula (HFNC), which partially relieved her work of breathing. The nasal swab for respiratory viruses was positive for enterovirus, and her urine culture grew Escherichia coli. She was transferred to the pediatric ward after clinical improvement on day 3. Echocardiography performed for evaluation of pulmonary hypertension estimated normal pressures but revealed a vascular ring anomaly. A computed tomography (CT) angiography performed confirmed the presence of an aberrant left pulmonary artery also referred to as a left pulmonary artery sling (LPAS) [Figure 1A].

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: Immunoglobulin 4 (IgG4) is the least abundant immunoglobulin in the sera of healthy individuals; however, its levels can vary in different diseases such as IgG4-related disease (high) or Sjögren's syndrome (low). While previous studies have suggested the importance of IgG4 in autoimmune diseases, the clinical and biological significance of high or low levels remains unclear.

Objectives: To investigate the association between IgG4 antibody levels and systemic sclerosis (SSc), as well as the clinical features of the disease.

Methods: We measured IgG4 levels in the sera of 74 SSc patients from the years 2000 to 2019 and compared them to IgG4 levels in 80 healthy donors from the Israeli national blood bank. We performed correlation analyses between IgG4 levels and various factors, including age, sex, disease subtype, disease duration, organs involved, and medications taken by the patients.

Results: Our findings revealed significantly lower IgG4 levels in SSc patients compared to healthy participants. SSc patients receiving steroid treatment exhibited prominently lower IgG4 levels. In addition, SSc patients with Raynaud's phenomenon tended to have lower IgG4 levels compared to those without Raynaud's phenomenon.

Conclusions: Our study demonstrates that IgG4 levels are lower in SSc patients. Further research is needed to elucidate whether this observation contributes to the etiology of the disease or if it represents a common manifestation among other autoimmune diseases.

Background: Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).

Objectives: To understand the association between depression and CVD, especially in young women.

Methods: We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.

Results: We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.

Conclusions: Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.

Myositis is described as any disease-causing inflammation in muscles. Muscle weakness is the most common symptom. Etiology includes infection, injury, medication side effects, and autoimmune conditions. The treatment varies according to the cause [1]. Statin induced necrotizing autoimmune myopathy (SINAM) is an exceptionally rare yet devastating complication of statin therapy that can occur at any time after initiation. The condition is also known as anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody (anti-HMGCR antibody) myopathy. SINAM should be considered in patients who develop proximal muscle weakness and marked elevated creatine phosphokinase (CPK) while taking statin therapy [2]. We report on a patient who presented with excessive fatigue, generalized muscle pain, and weakness without dysphagia.

Background: The coronavirus disease 2019 (COVID-19) pandemic showed the need to evaluate disease severity promptly at the time of hospital admission. 

Objectives: To establish an admission protocol, which included clinical and laboratory findings. 

Methods: We conducted a retrospective study at Wolfson Medical Center, Israel, for a period of 19 months (2020–2021). We established a protocol for patients who were admitted with COVID-19 infection. The protocol parameters included demographic data, co-morbidities, immune status, oxygen level at room air on admission, oxygen demand, lymphopenia, C-reactive protein (CRP) level, lactate dehydrogenase, D-DIMER, creatinine, aspartate transferase, alanine aminotransferase, and ferritin. Based on this protocol, we defined the severity of COVID-19 at the beginning of hospitalization and started treatment without delay. This protocol included ferritin levels as a guide to severity and outcome of patients. A database was established for all the parameters of the patients included in the study. 

Results: The study included 407 patients; 207 males (50.9%), 200 females (49.1%). The age range was 18–101 years. Hyperferritinemia (> 1000 ng/dl) was one of the strongest and most significant predictors for severe disease in these patients (P < 0.001). Lymphopenia, high levels of CRP, alanine aminotransferase, aspartate transferase, lactate dehydrogenase, and creatinine also correlated with severe disease, complications, and death. 

Conclusions: Abnormal ferritin levels were a very significant and clear indicator of the development of severe COVID-19. The addition of ferritin levels to our protocol aided in finding which patients were at increased risk for morbidity and mortality.

Background: Little is known about audiovestibular function in psoriasis, a chronic systemic inflammatory disease that affects 2% of the world’s population.

Objective: To investigate audiovestibular function in patients with psoriasis.

Methods: In this prospective case-control trial, we enrolled 33 patients with psoriasis and 30 healthy controls. Audiologic testing included audiometry, tympanometry, and otoacoustic emissions recording. The vestibular investigation consisted of a dizziness handicap inventory questionnaire, a complete clinical vestibular examination, and video head impulse testing.

Results: The psoriasis group showed significantly higher average hearing thresholds in both ears at all frequencies. Otoacoustic measurements differed significantly at 3000 Hz in the right (P = 0.026) and left ear (P = 0.034). The average dizziness handicap score was considerably higher in the psoriasis group, with a mean difference of 7.70 (P = 0.025). The number of patients with abnormal right anterior semicircular canal gain values was significantly higher in the psoriasis group (P = 0.047). Saccade analysis in the psoriasis group showed significantly higher number of patients with covert corrective saccades of the left posterior canal (P = 0.037) and significantly higher number of patients with abnormal interaural difference of corrective saccades in the plane of the right anterior-left posterior canals (P = 0.035).

Conclusions: The study demonstrates an association between psoriasis and audiovestibular impairment, which can affect quality of life. These results suggest that patients with psoriasis may be evaluated with audiometry for possible hearing loss. Vestibular testing may be pursued as clinically indicated.

Esophageal lung is a rare congenital malformation. We present a case of a full-term infant with an esophageal lung presenting as a white lung combined with VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) and dysmorphic features. A right pneumonectomy was successfully performed.

Background: Cloacal malformation represents the rarest and most complex congenital anorectal malformation in females and is characterized by the convergence of urinary, gynecological, and intestinal systems within a single common channel. Three-dimensional computed tomography reconstruction (3D CT cloacagram) has emerged as a valuable method for anatomical assessment and preoperative planning.

Objectives: To evaluate our experience with 3D CT cloacagram and assess its results.

Methods: This retrospective case series included all patients with cloacal malformation who underwent preoperative 3D CT cloacagram at a single institution during 2019–2023. Collected data included patient characteristics, timing of the 3D CT cloacagram, results of the 3D CT cloacagram, comparison with endoscopic results, surgical procedures, and postoperative outcome.

Results: Six patients with cloacal malformation were included in this study, including two with posterior cloaca. The median common channel length on 3D CT cloacagram was 24.5 mm (range 9–48 mm) and the median urethral length was 15.5 mm (range 13-24 mm). The surgical approach involved a combined abdominoperineal approach in three patients and posterior sagittal anorectal vaginal urethral plasty in one patient. Two patients were awaiting surgical reconstruction at the time of publication.

Conclusions: Our implementation of 3D cloacagram has facilitated precise measurements of both the urethra and common channel lengths, two key factors in formulating surgical strategies for cloacal reconstruction. Moreover, this technique has markedly improved our capacity for surgical planning contributing to colorectal, gynecological, and urological perspectives.

Background: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation.

Objectives: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles.

Methods: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the β-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay.

Results: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015).

Conclusions: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.

We report a rare case of an epidural abscess caused by Aggregatibacter aphrophilus in a 69-year-old healthy woman. The patient, presented with neck pain, high fever, and chills following dental treatment. A magnetic resonance imaging (MRI) scan revealed an epidural abscess with moderate spinal cord compression at the C4–C5 level. Surgical intervention and antibiotic therapy with ceftriaxone led to complete recovery. This case underscores the significance of considering A. aphrophilus as a potential pathogen in patients with neck pain and fever post-dental procedures and as a cause of abscesses in apparently healthy patients.

A. aphrophilus, a gram-negative coccobacillus, is part of the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), a group of bacteria mainly known for its association with endocarditis [1]. However, A. aphrophilus is an uncommon pathogen for epidural abscesses [2]. Our case illustrates its potential to cause an epidural abscess after dental manipulation.

Background: Pelvic organ prolapse in pregnancy is rare. Consequent complications include cervical infection, spontaneous abortion, and premature birth. Conservative management by means of a pessary have been described as improving maternal symptomatology and minimizing gestational risk. The delivery mode is controversial.

Objective: To describe the clinical courses of patients diagnosed with pelvic organ prolapse during pregnancy, and to present our multidisciplinary approach.

Methods: In this retrospective case series, we summarized the obstetrical outcomes of women diagnosed with pelvic organ prolapse during pregnancy in a single university-affiliated hospital.

Results: We identified eight women with advanced uterine prolapse at a mean age of 30.3 years. Seven were diagnosed with advanced uterine prolapse (Pelvic Organ Prolapse Quantification [POPQ] stage ≥ 3). All were treated by pessary placement, which was tolerable and provided symptomatic relief. The pessary type was chosen according to the prolapse stage. In women with cervical prolapse POPQ stage > 2 and cervical edema, a support pessary was less beneficial. However, the prolapse was well-controlled with a space-filling Gellhorn pessary. Low complication rates were associated with vaginal deliveries. The few complications that were reported included minor cervical laceration, postpartum hemorrhage, and retained placenta.

Conclusions: Treatment of pelvic organ prolapse during pregnancy must be individualized and requires a multidisciplinary approach of urogynecologists, obstetricians, dietitians, pelvic floor physiotherapists, and social workers. Conservative management, consisting of insertion of a vaginal pessary when prolapse symptoms appeared, provided adequate support for the pelvic floor, improved symptomatology, and minimized pregnancy complications. Vaginal delivery was feasible for most of the women.