Israel Medical Association Journal

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: 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: 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: 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: 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: Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower healthcare costs.

Objectives: To evaluate the implementation of the ERAS protocol and the effect on recovery during the hospitalization period after gynecological laparotomy surgeries.

Methods: We compared demographic and clinical data of consecutive patients at a single institute who underwent open gynecological surgeries before (August 2017 to December 2018) and after (January 2019 to March 2020) the implementation of the ERAS protocol. Eighty women were included in each group.

Results: The clinical and demographic characteristics were similar among the women operated before and after implementation of the ERAS protocol. Following implementation of the protocol, decreases were observed in post-surgical hospitalization (from 4.89 ± 2.56 to 4.09 ± 1.65 days, P = 0.01), in patients reporting nausea symptoms (from 18 (22.5%) to 7 (8.8%), P = 0.017), and in the use of postoperative opioids (from 77 (96.3%) to 47 (58.8%), P < 0.001). No significant changes were identified between the two periods regarding vomiting, 30-day re-hospitalization, and postoperative minor and major complications.

Conclusions: Implementation of the ERAS protocol is feasible and was found to result in less postoperative opioid use, a faster return to normal feeding, and a shorter postoperative hospital stay. Implementation of the protocol implementation was not associated with an increased rate of complications or with re-admissions

Background: The learning curve for transition from open to laparoscopic proctectomies is difficult. Most surgeons have considerable laparoscopic experience prior to performing robotic-assisted procedures. There are data regarding the transition from open to robotic proctectomies. Minimally invasive anterior resection for rectal cancer has gained widespread popularity in recent years, especially when using a robotic platform.

Objectives: To analyze the experience to the transition from open to robotic anterior resection for rectal cancer.

Methods: We performed a retrospective analysis of a computerized database. All patients who had a robotic-assisted proctectomy between December 2016 and March 2019 were included and were compared to patients who underwent an open anterior resection in the same time period. A single experienced colorectal surgeon with no prior experience in colorectal laparoscopic surgery performed the procedures.

Results: During the study period, 55 patients underwent robotic-assisted proctectomy and 55 had an open proctectomy. Patients had similar pre-operative demographic and clinical characteristics with the majority of patients receiving neoadjuvant chemoradiation. The surgical time was significantly lower in the open surgery group (168 minutes vs. 310 minutes, P = 0.005). Both the surgical and pathological outcomes did not differ significantly between the two groups, with good short-term oncologic outcomes and low complication rates.

Conclusions: The transition from open to robotic-assisted proctectomy is feasible and safe and provides a good alternative for undertaking a minimally invasive surgery for the experienced open colorectal surgeon

Background: Patients with severe coronavirus disease-2019 (COVID-19) are susceptible to superimposed infections.

Objectives: To describe COVID-19 patients who presented with complications due to Candida bloodstream co-infection (candidemia) and their outcome in a single center in northern Israel (Emek Medical Center) during the second outbreak of COVID-19 in Israel (15 June 2020 to 20 September 2020).

Methods: A retrospective study of COVID-19 patients presenting with candidemia was conducted, including clinical and laboratory data. The incidence of candidemia among hospitalized COVID-19 patients was compared to a historical cohort of non-COVID-19 controls.

Results: Three COVID-19 patients complicated with candidemia were documented. All three patients died shortly after the detection of candidemia. Three different Candida sp. were isolated from the blood cultures: C. albicans, C. parapsilosis, and C. glabrata. The incidence of candidemia among COVID-19 patients was 0.679 episodes per 1000 hospital days.

Conclusions: Our small sample suggests a much higher incidence of candidemia among COVID-19 patients compared to a historical cohort of non-COVID-19 controls. All clinicians treating COVID-19 patients in GICU should be aware of this complication

Background: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce.

Objectives: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia.

Methods: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level.

Results: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas.

Conclusions: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

Background: Surgical myotomy is the best therapeutic option for patients with achalasia. The minimally invasive technique is considered to be the preferred method for many surgeons. Robotic-assisted laparoscopic myotomy has several advantages over conventional laparoscopic surgery. These benefits include more accurate incisions that may result in a lower rate of intra-operative complications.

Objective: To describe our technique of performing robotic-assisted Heller myotomy and to review the initial results of this procedure.

Methods: All patients undergoing robotic-assisted Heller myotomy for achalasia between the years 2012–2018 at Rabin Medical Center were retrospectively reviewed from our institutional prospective database.

Results: Thirty patients underwent robotic-assisted Heller myotomy for achalasia. Mean operative time was 77 minutes (range 47–109 minutes) including docking time of the robotic system. There were no cases of conversion to laparoscopic or open surgery. There were no cases of intra-operative perforation of the mucosa. None of the patients had postoperative morbidity or mortality. Good postoperative results were achieved in 25 patients. Four patients required additional intervention (3 had endoscopic dilatations and 1 with known preoperative endstage achalasia had undergone esophagectomy). One patient was lost to follow-up.

Conclusions: Robotic-assisted Heller myotomy is a safe technique with a low incidence of intra-operative esophageal perforation compared to the laparoscopic approach. We believe that robotic-assisted surgery should be the procedure of choice to treat achalasia

Background: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease with the presence of autoantibodies, rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA). The presence of RF or ACPA predicts RA severity. Data on the influence of ACPA titer on RA course are limited.

Objectives: To determine the correlation between ACPA titers at the time of RA diagnosis to RA features and severity during 3 years of follow-up.

Methods: We performed a retrospective study of RA patients treated at our institution during the years 2006–2015 with known ACPA titers at RA diagnosis who completed at least 3 years of follow-up. Patients (N=133) were divided according to ACPA titer: seronegative (< 15 U/ml, n=55), weakly positive (15–49 U/ml, n=18), moderately positive (50–300 U/ml, n=29), and strongly positive (> 300 U/ml, n=31). Patient data, including disease activity score (DAS28), bone erosion on hand and/or foot X-rays, treatments with corticosteroids and disease-modifying-anti-rheumatic drugs (DMARDs), and hospitalizations, were recorded. Chi-square and Mann-Whitney method were used for statistical analysis. P < 0.05 was considered as statistically significant.

Results: Male gender, smoking, and RF positivity correlated with ACPA positivity and higher ACPA titers. There was no correlation between ACPA titer and the variables defined as representing RA severity: higher DAS28, bone erosions, hospitalizations, need for corticosteroids, and conventional and biological DMARDs.

Conclusions: Titer of ACPA was not identified as a predictive factor for RA severity

Background: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease.

Objectives: To determine the relation between natural AECA levels and prognosis related to coronary artery disease.

Methods: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up.

Results: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram.

Conclusions: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography