Israel Medical Association Journal

Background: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure.

Objectives: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question.

Methods: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts.

Results: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145–0.778, P = 0.01, median 34 vs. 28, interquartile range 28–48, 23–35 years, P = 0.02, respectively).

Conclusions: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.

Background: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

Objectives: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest©.

Methods: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two‐dimensional SWE or FibroTest©; APRI and FIB-4 scores.

Results: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6–33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5–100), 13.4 kPa (range 5.5–51) at 6 months, and 11.4 kPa (range 6.1–35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

Conclusions: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis

Background: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2–8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis.

Objectives: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS.

Methods: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS.

Results: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group.

Conclusions: FMS has certain inflammatory components that may be useful in disease diagnosis

Background: For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation.

Objectives: To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR.

Methods: Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used.

Results: In the study 140 patients with II–III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets.

Conclusions: We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.

Background: Keratoconus is a non-inflammatory disease characterized by progressive corneal steepening, which leads to decreased visual acuity secondary to high irregular astigmatism.

Objectives: To compare the one-year outcomes of accelerated vs. standard collagen crosslinking (CXL) in the treatment of keratoconus.

Methods: A database search of patients who underwent CXL from 2009 to 2017 was conducted at the cornea clinic at Sheba Medical Center. Charts of 99 adult patients (124 eyes) were reviewed. All patients were diagnosed with keratoconus. Main outcome measures were change in keratometry, uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA).

Results: We evaluated outcomes in two groups: CXL with standard (3 mW/cm² for 30 minutes) vs. the accelerated (9 mW/cm² for 10 minutes) protocol. There were no significant differences between the groups with regard to BCVA, UCVA, and mean spherical equivalent (P =0.83, 0.0519, 0.181, respectively). The corneal thickness in the center and thinnest location were higher in the accelerated group than the in the standard group (P = 0.126). Complication rates did not differ between the two groups.

Conclusions: Accelerated and standard CXL are both safe and effective techniques. Accelerated CXL confers the added benefit of being a faster procedure to both patients and surgeons.

Background: Hip fracture is common in elderly patients and is associated with high morbidity and mortality. Acute kidney injury (AKI) following hip fracture may have additional impact on clinical outcomes.

Objectives: To investigate the incidence of AKI, the risk factors for its occurrence and impact on mortality, timing of surgery, and length of hospitalization (LOS) in patients undergoing hip fracture surgery.

Methods: We retrospectively examined the records of patients who underwent hip fracture surgery between 2013 and 2017. All patients had a baseline serum creatinine value and at least one later value. AKI was defined according to KDIGO guidelines.

Results: The study included 511 patients. Mean age was 72.6 years, 325 males (63.4%); 151 (29.5%) had baseline eGFR < 60 ml/min/1.73m². Of these, 87 (17%) developed AKI. Older age, diabetes mellitus, hypertension, and chronic heart condition were significantly more common in patients who developed AKI. Patients with AKI had increased 30-day mortality (hazard ratio [HR] 3.96, 95% confidence interval [95%CI] 1.62–9.7, P = 0.003) and mortality at one year (HR 2.72, 95%CI 1.5–4.9, P = 0.002). AKI was associated with surgery delay > 48 hours (HR 2.241, 95%CI 1.206–4.165, P = 0.011). Mean LOS was 10.9 days and 8 days for patients with AKI and without, respectively, P < 0.0001.

Conclusions: AKI is a common complication in patients with hip fracture and is associated with increased short- and long-term mortality, delayed surgery, and longer hospitalization. Interventions identifying and monitoring patients at risk may contribute to improve the outcomes

Background: Toward the end of 2019, the coronavirus disease-2019 (COVID-19) pandemic began to create turmoil for global health organizations. The illness, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), spreads by droplets and fomites and can rapidly lead to life-threatening lung disease, especially for the old and those with health co-morbidities. Treating orthopedic patients, who presented with COVID-19 while avoiding nosocomial transmission, became of paramount importance.

Objectives: To present relevant methods for pandemic control and hospital accommodation with emphasis on orthopedic surgery.

Methods: We searched search PubMed and Google Scholar electronic databases using the following keywords: COVID-19, SARS-CoV-2, screening tools, personal protective equipment, and surgery triage.

Results: We included 25 records in our analysis. The recommendations from these records were divided into the following categories: COVID-19 disease, managing orthopedic surgery in the COVID-19 era, general institution precautions, triage of orthopedic surgeries, preoperative assessment, surgical room setting, personal protection equipment, anesthesia, orthopedic surgery technical precautions, and department stay and rehabilitation.

Conclusions: Special accommodations tailored for each medical facility, based on disease burden and available resources can improve patient and staff safety and reduce elective surgery cancellations. This article will assist orthopedic surgeons during the COVID-19 medical crisis, and possibly for future pandemics

Background: Coronavirus disease-19 (COVID-19) impacted medical education and led to the significant modification or suspension of clinical clerkships and rotations.

Objectives: To describe a revised surgery clerkship curriculum, in which we divided in-person clinical teaching into smaller groups of students and adopted online-based learning to foster student and patient safety while upholding program standards.

Methods: The third-year surgery core clerkship of a 4-year international English-language program at the Medical School for International Health at Ben Gurion University of the Negev, Beer Sheva, Israel, was adapted by dividing students into smaller capsules for in-person learning and incorporating online learning tools. Specifically, students were divided evenly throughout three surgical departments, each of which followed a different clinical schedule.

Results: National Board of Medical Examiners clerkship scores of third-year medical students who were returning to in-person clinical clerkships after transitioning from 8 weeks of online-based learning showed no significant difference from the previous 2 years.

Conclusions: To manage with the restrictions caused by COVID-19 pandemic, we designed an alternative approach to a traditional surgical clerkship that minimized the risk of exposure and used online learning tools to navigate scheduling challenges. This curriculum enabled students to complete their clinical rotation objectives and outcomes while maintaining program standards. Furthermore, this approach provided a number of benefits, which medical schools should consider adopting the model into practice even in a post-pandemic setting

Background: In rheumatoid arthritis (RA), females usually have a worse prognosis. To date, the influence of physician gender in the evaluation of RA activity is still largely unknown.

Objectives: To investigate the discrepancy in RA disease activity assessment between male and female physicians and to compare patient and evaluator perception of disease activity and global health (GH) status.

Methods: One female and one male rheumatologist evaluated 154 RA patients recording tender and swollen joint count, GH, evaluator global assessment (EGA), and patient global assessment (PGA) disease activity. A third rheumatologist calculated DAS28, CDAI, and SDAI. Difference was evaluated by Wilcoxon test. Physician–patient agreement was assessed by intraclass correlation coefficient.

Results: GH, PGA, and DAS28 were higher when recorded by the female examiner. Male EGA was higher than female. Among male patients, PGA was higher when collected by the female examiner. The probability of being judged as having an active disease did not rely on physician gender. The agreement with the physician’s evaluation of disease activity was high. PGA values were higher than EGA in both examiners. The physician–patient agreement was moderate for the male examiner and good for the female. The female physician had a higher agreement with both genders.

Conclusions: Subjective measure of disease activity differs between female and male rheumatologists, contributing to a different evaluation of disease activity. Patients have a higher perception of disease activity compared to physicians. The stronger agreement between female physicians and patients may be related to a more emphatic setting established by the female physician

Background: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation.

Objectives: To verify whether high MPV values discovered incidentally in healthy naïve patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes.

Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naïve patients (without any known cause of an abnormal high MPV, greater than  upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome).

Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency of pre-diabetes. Family doctors more frequently meet naïve patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding and search for a hidden pre-diabetes or metabolic syndrome.

Conclusions: High MPV values discovered incidentally in healthy naïve subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease

Background: Eye trauma is an unfortunate and often preventable cause of vision loss. Confetti cannons are common causes of injury. Awareness of ocular hazards of confetti cannons remains low because of limited reports describing ophthalmic injuries following their use.

Objectives: To describe outcomes of ocular trauma caused by confetti cannons and to increase recognition of their ocular risks.

Methods: A retrospective analysis was conducted of eye injuries caused by confetti cannons presenting to a single medical center between 2016 and 2020. Data collected included age, gender, eye injured, ocular damage, visual outcome, and details of surgeries performed.

Results: Overall, six consecutive patients (2 males, mean age 19.5 ± 9.74 years) were identified and studied. In all patients only one eye was injured (3 right eyes) during a private celebration, most commonly (n=5) to a bystander while in the vicinity of a cannon operated by someone else. Most common eye injuries included corneal erosion (n=4), traumatic hyphema (n=4), and retinal edema (n=3). Mean initial logMAR visual acuity in the injured eye was 0.73 ± 0.18, improving to 0.25 ± 0.16 at the final visit (P = 0.125). Two patients underwent eye surgery due to their trauma: one to repair globe penetration and another to undergo intravitreal injection of tissue plasminogen activator and C3F8 for submacular hemorrhage, followed 8 months later by intravitreal bevacizumab injection for choroidal neovascularization.

Conclusions: Confetti cannons pose hazards that can cause severe ocular trauma resulting in permanent vision loss. Increasing awareness of device hazards is necessary to prevent eye injuries

Background: The recent increase in enterococcal urinary tract infections (EUTI) and the potential morbidity and mortality associated with inappropriate antimicrobial treatment underscores the need for early risk assessment and institution of appropriate empirical antimicrobial therapy.

Objectives: To identify high-risk features associated with hospitalized patients with EUTI.

Methods: Demographic, clinical, laboratory, and bacteriological data of 285 patients hospitalized with UTI during 2016 were retrieved from the computerized database of Shamir Medical Center. Patients were divided into two groups: EUTI and non-EUTI (NEUTI), according to the presence or absence of enterococcus in the urine culture. The features of the two groups were compared.

Results: We obtained 300 urine cultures from 285 patients. Of the total, 80 patients (26.6%) had EUTI and 220 patients (73.3%) had NEUTI. A higher prevalence of urinary multi-bacterial cultures was found in EUTI compared to NEUTI patients (P < 0.01). Higher prevalence of permanent indwelling urinary catheter and dementia were found in hospitalized patients with community-acquired EUTI and nosocomial EUTI respectively (P = 0.02, P = 0.016) compared to patients with NEUTI.

Conclusions: Indwelling urinary catheter and dementia are risk factors for EUTI in patients with community and hospital acquired infection, respectively

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems.

Objectives: To compare the two systems for accuracy of cancer risk prediction.

Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared.

Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively.

Conclusion: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems