Israel Medical Association Journal

Common variable immunodeficiency (CVID) is a heterogeneous primary immune deficiency disorder characterized mainly by defective B lymphocyte differentiation, leading to hypogammaglobinemia and defective antibody production. It is often combined with cellular immune defects. A minority of patients present during childhood and adolescence. Infections are most often sinopulmonary but can affect any system. The noninfectious complications include progressive lung disease, autoimmunity, gastrointestinal inflammatory disease, liver disease, granulomatous disease, lymphoid hyperplasia and infiltrative disease, and the development of lymphoma and other cancers. In addition to recurrent infections and bronchiectasis, patients may develop chronic interstitial lung disease, granulomatous lung disease, lymphoma, and pulmonary hypertension.

Background: Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.

Objectives: To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.

Methods: A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.

Results: The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).

Conclusions: Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.

Background: Surgery for hip fractures within 48 hours of admission is considered standard. During the lockdown period due to the coronavirus disease-2019 (COVID-19) epidemic, our medical staff was reduced.

Objectives: To compare the demographics, treatment pathways, and outcomes of patients with hip fractures during the COVID-19 epidemic and lockdown with the standard at routine times.

Methods: A retrospective study was conducted of all patients who were treated surgically for hip fracture in a tertiary center during the COVID-19 lockdown period between 01 March and 01 June 2020 and the equivalent period in 2019. Demographic characteristics, time to surgery, surgery type, hospitalization time, discharge destination, postoperative complications, and 30- and 90-day mortality rates were collected for all patients.

Results: During the COVID-19 period, 105 patients were operated due to hip fractures compared to 136 in the equivalent period with no statistical difference in demographics. The rate of surgeries within 48 hours of admission was significantly higher in the COVID-19 period (92% vs. 76%, respectively; P = 0.0006). Mean hospitalization time was significantly shorter (10 vs. 12 days, P = 0.037) with diversion of patient discharge destinations from institutional to home rehabilitation (P < 0.001). There was a significant correlation between the COVID-19 period and lower 90-day mortality rates (P = 0.034). No statistically significant differences in postoperative complications or 30-day mortality rates were noted.

Conclusions: During the COVID-19 epidemic, despite the limited staff and the lack of therapeutic sequence, there was no impairment in the quality of treatment and a decrease in 90-day mortality was noted.

Background: Point shear-wave elastography (pSWE) is a new method to assess the degree of liver fibrosis. It has been shown to be effective in detecting stiffness in viral hepatitis.

Objectives: To determine the feasibility of pSWE for assessing liver stiffness and fibrosis in liver diseases of different etiologies.

Methods: This prospective single-center study included a population of adult patients with chronic liver diseases from different etiologies, who were scheduled for liver biopsy, and a control group of healthy adults who prospectively underwent pSWE. Ten consecutive pSWE measurements of the liver were performed using a Philips iU22 ultrasound system. Stiffness degree was compared to liver biopsy results. Fibrosis degree was staged according to METAVIR scoring system.

Results: The study group was comprised of 202 patients who underwent liver biopsy and pSWE test and a control group consisting of 14 healthy adults who underwent pSWE for validation. In the study group, the median stiffness was 5.35 ± 3.37 kilopascal (kPa). The median stiffness for F0–1, F2, F3, and F4 as determined by liver biopsy results were 4.9 kPa, 5.4 kPa, 5.7 kPa, and 8 kPa, respectively. The median stiffness in the control group was 3.7 ± 0.6 kPa. Subgroup analyses were conducted for viral hepatitis vs. non-viral hepatitis and steatohepatitis vs. non-steatohepatitis groups.

Conclusions: pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values

Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed.

Objectives: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores.

Methods: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month.

Results: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005).

Conclusions: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.

Background: While the routine performance of terminal ileum (TI) intubation during colonoscopy procedures is perceived to have a low yield, its utility during colonoscopies performed for specific indications have not been well studied.

Objectives: To assess the diagnostic yield of an indication-based ileoscopy in real-life practice.

Methods: The authors reviewed endoscopic reports of patients who underwent colonoscopies over an 8-year period (2011–2018) and had routine ileoscopy during these procedures. Demographic data, indications for colonoscopy, and endoscopic findings were documented. Diagnostic yield and odds ratio for TI findings were calculated.

Results: Over 30,000 colonoscopy reports performed during the study period were reviewed. Ilesocopy was performed in 1800 patients, 216 patients had findings in the TI (ileitis or ulcers). TI findings were more prevalent in younger ages (38.3 ± 17.6 vs. 43.6 ± 20, P < 0.05). The greatest yield of ileoscopy was evident when performed for the evaluation of chronic abdominal pain and diarrhea (14.4% vs. 9.3%, odds ratio [OR] 1.62, P < 0.05). Positive fecal occult blood test (FOBT) (OR 0.1, 95% confidence interval [95%CI] 0.02–0.5, P = 0.005) and constipation (OR 0.44, 95%CI 0.2–0.9, P = 0.04) were negatively associated with TI findings.

Conclusions: Ileoscopy may have the greatest utility in evaluating suspected inflammatory bowel disease (IBD) patients, but may not add value to the evaluation of constipation and positive FOBT

Background: Bariatric surgery has become the most common and effective therapeutic option for obesity. However, it is associated with morbidity and complications. Identification of predictors for surgical complications is an unmet need.

Objectives: To determine a simple non-invasive parameter that predicts early postoperative complications following bariatric surgery.

Methods: In this retrospective study of all patients who underwent elective bariatric surgery at Nazareth Hospital EMMS during a 4-year period (2015–2018). We collected clinical and laboratory parameters and determined predictors of complications.

Results: A total of 345 patients underwent bariatric surgery during the study period. Of the patients, 51 experienced early post-bariatric surgery complications as compared to 294 patients who had no complications. Univariate analysis revealed that neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] 1.912, P < 0.0001) and platelet to lymphocyte ratio (OR 1.015, P < 0.0001) were associated with post-bariatric surgery complications. In a multivariate logistic regression analysis, only NLR remained a significant predictor (OR 1.751, 95% confidence interval 1.264–2.425, P = 0.0008) with a receiver operating characteristic curve for NLR of 0.8404.

Conclusions: We found that the NLR predicts post bariatric surgery early complications. Further prospective studies are needed to validate our findings.

Background: Buried bumper syndrome (BBS) mostly occurs as a late complication after percutaneous endoscopic gastrostomy (PEG) insertion; however, early BBS has been rarely reported, and the treatment of this condition is still unclear.

Objectives: To evaluate the Seldinger technique for treatment of early BBS after PEG insertion.

Methods: We report two cases of early BBS in two consecutive patients who underwent PEG insertion to maintain oral intake. The first patient was an 83-year-old woman showing Alzheimer type dementia, while the other one was a 76-year-old man who presented with maxillary cancer and treated with radiotherapy followed by left maxillectomy. Post-surgery, he developed progressive difficulty of swallowing due to mouth deformation and treatment related nerve toxicity. The first patient presented with fever and purulent discharge from the gastrostomy insertion site, without ability to rotate or slide the tube through the stoma 10 days after the PEG insertion. The man was admitted to the hospital 5 days following PEG insertion due to a fever of 38°C and peritubal swelling with purulent discharge. In addition, the tube could not rotate or slide through the stoma.

Results: Buried bumper syndrome was demonstrated by computed tomography scan. Gastroscopy and gastrostomy tube replacement was performed successfully according to the Seldinger technique (replacement over guidewire) in both cases. Correct intragastric tube positioning was demonstrated radiographically before resuming tube feeding. The two patients were discharged in good physical condition several days later.

Conclusions: External replacement over guide wire should be considered in such cases.

Background: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin.

Objectives: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin.

Methods: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information.

Results: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity.

Conclusions: Histomorphometry may help to predict a patient's response to treatment at an early stage.

Background: Autoimmune hepatitis (AIH) may be associated with other autoimmune diseases. Autoantibodies are common in AIH suggesting their potential role in the pathogenesis of the disease. Among these autoantibodies, thyroid autoantibodies have been reported in patients with chronic hepatitis, with greater prevalence in patients with chronic hepatitis C infection.

Objectives: To assess the prevalence of thyroid dysfunction among patients with AIH.

Methods: In this case-control, retrospective study, we examined patients diagnosed with AIH according to both the original and revised international AIH group scoring systems. Patients with other hepatic pathologies were excluded AIH was evaluated as an independent risk factor for thyroid disease by a logistic regression model. Univariate and multivariate regression analyses were conducted using hypothyroidism and hyperthyroidism as the dependent variables.

Results: Our cohort comprised 163 patients diagnosed with AIH and 1104 healthy age- and gender-matched controls. Hypothyroidism was more prevalent among those with AIH compared to controls (17.7% vs. 5%, respectively, 95% confidence interval [95%CI] 1.68–2.48, P <  0.001). Hyperthyroidism was more prevalent in AIH patients compared to controls (odds ratio 3.2% and 1.2%, respectively, 95%CI 1.68–2.47, P <  0.001). Using a multivariate logistic analysis, we found an independent association between AIH and hypothyroidism but not with hyperthyroidism.

Conclusions: Thyroid dysfunction is more prevalent in patients with AIH. Whether thyroid dysfunction is the cause or a risk factor for AIH, or vice versa, is still unclear. Screening for thyroid dysfunction is warranted after AIH is diagnosed.

Autoimmune pancreatitis (AIP) is a rare disease that has been classified into two subtypes. Type 1 is believed to be mediated by immunoglobulin G4 (IgG4) and type 2 is related to granulocytic epithelial lesions, but the pathogenetic mechanisms in both are still unknown. The patho-mechanism of AIP type 1 is suggested to be secondary to autoimmunity or allergy due to the increased serum IgG4 and immunoglobulin E levels, abundant infiltration of IgG4, plasmacytes and lymphocytes in the pancreas, and fibrosis. Both types of AIP respond to steroid treatment. The relapse rate after remission is high and reaches 30–50% within 6–12 months in AIP type 1; however, in AIP type 2 relapse is rare. The maintenance therapy and therapeutic strategy for relapsing patients with type 1 is managed with low dose steroids, however there are no consensus guidelines. In this review we discuss the current understanding of AIP, highlighting the emerging potential role of eotaxin in pathogenesis, classification, and management of the disease

Background: With the widespread use of antifungal agents, the frequency of non-albicans Candida (NAC) blood-stream infections (BSI) is increasing.

Objectives: To describe the epidemiology, clinical manifestations, and risk factors for NAC BSI, focusing on prior antifungal and immunosuppressive therapy.

Methods: The authors conducted an observational, retrospective cohort study among adult patients with candidemia at the Rambam Health Care Campus, a tertiary medical center in Israel, between 2009 and 2015. Comparisons between patients with Candidemia albicans and NAC candidemia were performed. Regression analysis, with NAC BSI as the dependent variable and significant risk factors for NAC as independent variables, was performed.

Results: A total of 308 episodes of candidemia were included. C. albicans was isolated in 30.8% of patients (95/308), while NAC spp. were isolated in the rest. Significant independent risk factors for NAC included immunosuppression therapy (odds ratio [OR] 0.38, 95% confidence interval [95%CI] 0.19–0.76) and previous azole use (OR 0.2, 95%CI 0.06–0.710). The interaction between prior azole and immunosuppression therapy in the model was not significant, and after its inclusion in the model only immunosuppression remained significantly associated with NAC. In the subgroup of patients who did not receive prior azoles, immunosuppression therapy, neutropenia, and bone marrow transplantation were significantly associated with NAC.

Conclusions: Independent of previous azole treatment, immunosuppressive therapy was a significant risk factor for NAC in our cohort.

Background: The prevalence of Helicobacter pylori varies geographically by age, race, and socioeconomic status (SES). However, the impact of ethnicity on endoscopic outcomes in infected individuals is not well known.

Objectives: To assess the impact of ethnicity among Israelis with biopsy-proven H. pylori infection.

Methods: A retrospective study, including patients who underwent gastroscopy and were diagnosed histologically with H. pylori infection, was conducted. Information on demographics, SES, medications, and co-morbidities were extracted from medical records. Univariate (Student's t-test, chi-square test) and multivariate (multinomial and logistic) regression analysis were conducted to examine the predictors of the clinical outcome.

Results: The study included 100 Israeli Jews and 100 Israeli Arabs diagnosed with biopsy-proven H. pylori infection. At univariate analysis, the number of households was higher among Arabs (P < 0.001), whose family income and parental education were lower than among Jews (P < 0.001 for both variables). The response to amoxicillin and clarithromycin differed between the two groups, being higher among Jews (P < 0.001).In clinical outcomes (gastritis severity, gastric and duodenal ulcer, intestinal metaplasia, atrophic gastritis, and MALT), no statistically significant differences could be detected between Jews and Arabs. Concerning intestinal metaplasia, lack of consumption of nonsteroidal anti-inflammatory drugs resulted a statistically significant protective factor (odds ratio 0.128, 95% confidence interval 0.024–0.685, P = 0.016).

Conclusions: Although in the literature ethnicity seems to be a risk factor for H. pylori colonization, no statistical significance was detected in various endoscopic and histological findings related to H. Pylori infection between Israeli Arabs and Jews.