[TEN-HOUR INTERMITTENT FASTING PLUS MEDITERRANEAN DIET VERSUS MEDITERRANEAN DIET ALONE FOR TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)].

INTRODUCTION: Nonalcoholic Fatty Liver Disease (NAFLD) has become the leading cause of liver morbidity. The Mediterranean diet can improve NAFLD and may be offered as treatment. Intermittent fasting has been shown to improve aspects of the metabolic syndrome, but its effect on NAFLD is inconclusive. OBJECTIVES: A randomized - controlled study assessed the outcomes of the effect of the Mediterranean diet alone versus the Mediterranean diet in combination with intermittent fasting for 16 weeks in patients with NAFLD (1:2 ratio) and subsequent long term follow-up. Outcomes parameters included the response to treatment as measured by body mass index (height and weight), waist-hip ratio, and levels of steatosis and fibrosis as measured by transient elastography. In addition, satisfaction and compliance were assessed via questionnaires (ten-point Likert scale). RESULTS: Sixteen out of 40 recruited patients completed the study (69% men, mean age 45.8 ± 12.1 years, mean baseline BMI 33 ± 4.5), of which nine patients were included in the arm of diet in combination with intermittent fasting. The two groups were similar at baseline with regard to age, gender, height, weight, BMI, waist to hip ratio, and levels of steatosis and fibrosis. At the study end, a significant decrease was observed (p-value = 0.01) in the degree of steatosis from 316.4 ± 50.4 to 279 ± 35.7 DB/m. The improvement in steatosis was significant (p-value = 0.01) in the intermittent fasting group (an improvement of 13.8 ± 20.9%) as compared to the group without intermittent fasting (4.2 ± 20.9%, no statistical significance). The other physical outcome measures did not show a statistically significant change between values at the beginning of the study and study end (16 weeks). Participant questionnaires were completed at a mean follow-up of 1.6 ± 0.2 years and showed a high level (8.3 ± 1.69) of compliance at the beginning of the study in both groups. In addition, both study groups expressed a similar degree of difficulty in adhering to the assigned diet. By study end, participant adherence was significantly higher (p-value = 0.04) among the Mediterranean diet group alone (7 ± 2) as compared to the group in combination with intermittent fasting (4.9 ± 2). Furthermore, those in the Mediterranean diet alone group were more willing (9.7 ± 0.8) to continue the dietary treatment after completing the study as compared to the intermittent fasting group (6.4 ± 0.7) (p-value = 0.03). Study participants in both groups reported that their dietary treatment was overall beneficial (7.9 ± 2.2). CONCLUSIONS: This study, given the limitations of a small sample size, suggests that a Mediterranean diet in combination with intermittent fasting improves steatosis in NAFLD patients over the long term as compared to Mediterranean diet without time restricted eating.

Correction to: Antenatal Management for Women with Inflammatory Bowel Disease: Experience from Our 'IBD MOM' Clinic.

The original version of the article unfortunately contained tagging error in first and family name of authors Ariella Bar-Gil Shitrit and Ami Ben Ya'acov. This has been corrected with this erratum.

Antenatal Management for Women with Inflammatory Bowel Disease: Experience from Our 'IBD MOM' Clinic.

BACKGROUND: Inflammatory bowel disease affects women during their reproductive years and thus pregnancy outcomes. IBD MOM is a multidisciplinary, single-center clinic established to benefit women with IBD and their neonates. AIM: The aim of this study was to evaluate the perinatal outcomes of the IBD MOM clinic patients compared to patients who attended antenatal and gastrointestinal disease community clinics (IBD CC). METHODS: This single-center, prospective study was conducted from 2011 to 2015. The primary outcome was cesarean delivery; secondary was adverse perinatal outcomes. In parallel, a new pregnancy-oriented, disease severity score was evaluated for its association with perinatal risk (score low = 0 to severe = 5). RESULTS: We identified 90 women in the IBD MOM clinic and 206 in the IBD CC. Maternal age, smoking habits, pregnancy complications, and type of IBD (CD/UC) were similar between groups. Rates of labor induction and birth weight were also similar between IBD MOM and IBD GI. The IBD MOM overall preterm delivery (PTD) rate (< 37 weeks) was significantly higher 18.9 versus 9.7% (P = 0.028). The IBD MOM group had a significantly higher IBD MOM disease severity score that correlated with a higher rate of PTD. The overall IBD MOM score and scores > 3 were significantly associated with PTD risk in both groups (P = 0.013 and P = 0.004, respectively). CONCLUSION: Women with moderate and severe IBD who attended a multidisciplinary clinic may benefit from this unique center. Healthcare planning policies can assume that costly, multidisciplinary clinics for women with IBD should be reserved for those with moderate and severe disease.

The supine apprehension test helps predict the risk of recurrent instability after a first-time anterior shoulder dislocation.

BACKGROUND: We previously identified the positive result of the supine apprehension test after completion of rehabilitation following a first dislocation as a possible predictor of high risk for redislocation. We extend the follow-up of a previous cohort of patients with first-time shoulder dislocations to better assess this test. METHODS: Fifty-three men aged 17 to 27 years who sustained a first traumatic shoulder dislocation were treated by shoulder immobilization for 4 weeks and then rehabilitated with a standard physical therapy protocol. At 6-week follow-up, a supine anterior apprehension test was performed to assess the risk of redislocation. The patients were observed prospectively for a minimum of 75 months. RESULTS: Of the 53 participants, 52 (mean age, 20.2 years) completed the study follow-up. Of the 52 subjects, 41 (79%) were combat soldiers. Follow-up was between 75 and 112 months. Of the 52 subjects, 31 (60%) redislocated at a range of 3 to 70 months after the initial dislocation. Eleven of 14 subjects (79%; confidence interval, 52%-92%) with a positive anterior apprehension test result redislocated, compared with 20 of 38 patients (53%; confidence interval, 37%-68%) with a negative test result. Patients with a positive test result redislocated more and earlier (P = .02, PROC LIFETEST, SAS). CONCLUSIONS: The results of the supine apprehension test after a first shoulder dislocation and rehabilitation can help predict risk for recurrent instability. It potentially may be included as a variable in decision analysis models.

Comparison of knee SPECT and MRI in evaluating meniscus injuries in soldiers.

BACKGROUND: Medical evaluation of a suspected meniscus injury begins with a history-taking and physical examination. Suspected meniscus injuries not responding to treatment are usually sent for imaging to confirm the diagnosis before arthroscopy. Tc-MDP bone single photon emission computed tomography (SPECT) scan has been suggested as an alternative to magnetic resonance imaging (MRI) in evaluating suspected knee meniscus tears. OBJECTIVES: To examine the accuracy of knee SPECT as a tool to identify meniscus tears versus that of MRI as compared to the gold standard of arthroscopy. METHODS: The Israel Defense Forces database for 2005 through 2009 was searched using the key words: knee MRI, knee SPECT and knee arthroscopy. We identified 330 subjects who had undergone both a single knee SPECT and a single knee MRI prior to knee surgery. The medical files of 193 of the 330 subjects were randomly selected for review. A comparison was made between the preoperative SPECT and MRI studies and the arthroscopic finding. The sensitivity, specificity and accuracy were calculated. RESULTS: The subjects' age was 21.3 ± 3.9. The agreement between SPECT and arthroscopy was 0.14 forthe medial meniscus and 0.29 for the lateral meniscus. The agreement between MRI and arthroscopy was 0.59 for the medial meniscus and 0.69 for the lateral meniscus. SPECT scan was found to be 61% sensitive, 54% specific and 58% accurate in detecting common knee pathology, whereas MRI was found to be 95% sensitive, 67% specific and 85% accurate. CONCLUSIONS: Knee SPECT has a lower sensitivity, specificity and accuracy than MRI in evaluating meniscal injuries and its use can result in increased unnecessary surgery.

At long-term follow-up many first-time male traumatic shoulder dislocators remain symptomatic.

OBJECTIVES: To assess the status at 13 to 17 years follow-up of a cohort of young male traumatic shoulder dislocators. STUDY DESIGN: Prospective cohort study. METHODS: A prospective study of first-time young male traumatic shoulder dislocators, began in 2004. Subjects were evaluated by the apprehension test after completing rehabilitation 6 to 9 weeks post dislocation. Between March 2021 and July 2022, a telephone questionnaire was administered to ascertain their current shoulder status. Subjects were questioned about avoidance of activities of daily living and sport, participation in sports, current instability, and self-assessed shoulder function by the SANE score. RESULTS: 50/53 (94.3%) of the study subjects, mean age 20.4 years, completed a mean follow-up of 181.8 ±â€¯12 months. The non-redislocation survival was 13% for those with a positive apprehension test and 49% for those with a negative test (p = 0.007). SANE scores were 64.3 ±â€¯23.7 for those with a positive apprehension test and 83.7 ±â€¯19.7 for those with a negative test (p = 0.001). In the year before the follow-up, 33.3% of those treated conservatively and 42.9% treated surgically experienced subluxation (p = 0.5). Fifty-seven percent of those who were treated conservatively and 56% of those who underwent surgery avoided some ADL or sports because of their shoulder. CONCLUSIONS: For young male first time traumatic shoulder dislocators a positive apprehension test after rehabilitation is associated with a high risk for reoccurrence and poorer long-term results. Most subjects were still dealing with shoulder symptoms at long-term follow-up.

Patients with low ALT levels are at increased risk for severe COVID-19.

Introduction: Frailty is a known risk factor for many diseases, including COVID-19. However, many frail patients are undiagnosed as the diagnosis can be cumbersome. Alanine transaminase (ALT) is found not only in the liver but also in the muscle tissue, and multiple studies show that frail sarcopenic patients have lower ALT. Frail patients are at increased risk for severe COVID-19. We evaluated the association between pre-infection low ALT and the risk for severe COVID-19. Methods: We collected data regarding all subjects tested for SARS-CoV-2 between 1 March 2020 and 31 December 2021 from a national state-mandatory HMO in Israel, serving more than 1.3 million patients. Clinical and laboratory data were collected, including ALT from the year prior to infection. Severe COVID-19 was defined either as death, ICU admission, or ≥10 hospitalization days. Patients with low ALT (ALT ≤ 10 IU/l) were compared with patients with normal ALT (11-40 IU/l). Patients younger than 18 years with a diagnosis of liver disease and with ALT > 40 IU/l were excluded. Results: During the study period, 58,961 patients tested positive for SARS-CoV-2. The patients in the low ALT group were younger (40.53 vs. 42.73, p < 0.001), less likely to be males (12.3 vs. 38.7%, p < 0.001), and had lower BMI (25.97 vs. 27.15, p < 0.001). The patients in the low ALT group had higher mortality (2.36 vs. 0.57%, p < 0.001), more ICU hospitalizations (0.49 vs. 0.41%, p = 0.47), and more prolonged hospitalizations [2.63% (95% CI 2-3.2%) vs. 0.98% (95% CI 0.86-1.1%) p < 0.001]. In multivariate logistic regression analyses, low ALT was associated with an increased risk of severe COVID-19, with increased mortality (OR 1.88, 95% CI 1.37-2.56) and prolonged hospitalization (OR 1.78, 95% CI 1.33-2.35). Conclusion: Low ALT level prior to infection is a significant risk factor for morbidity and mortality from COVID-19 infection. Further studies are warranted to address treatment options for this population.

SARS-CoV-2 vaccine alleviates disease burden and severity in liver transplant recipients even with low antibody titers.

BACKGROUND AND AIMS: We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. PATIENTS AND METHODS: One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). RESULTS: In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. CONCLUSION: Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.

Weaker SARS-CoV-2 vaccine responses in nonalcoholic fatty liver disease with advanced liver fibrosis.

Background: SARS-CoV-2 vaccine responses that could harbor potential risks to chronic liver diseased patients. Aims: To assess immune response following Pfizer's SARS-CoV-2 vaccine in patients with different liver fibrosis severities of nonalcoholic fatty liver disease (NAFLD). Methods: Clinical and histological (NAS-score and fibrosis stage) characteristics of NAFLD patients before vaccine were correlated with serologic vaccine responses of two doses of the BNT162b2. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed on day seven following immunization (Liaison assay). Results: The mean-age of patients (n = 157) was 56.9 ± 13.2 years (46.5 % males). 94.8 % had a positive response (anti-S levels ≥ 19 AU/ml). The anti-S cutoff of 200 AU/ml used to separate strong vs. weak responses. A strong response (anti-S titers ≥ 200 AU/ml) was observed in 93/157 (59.2 %) patients with a mean-age of 53.1 ± 13.8 years (45.2 % males). A weak response (anti-S titers < 200 AU/ml) was observed in 64/157 (40.8 %) cases with a mean-age of 62.3 ± 10.2 years (p < 0.0001). The strong response subgroup had lower metabolic comorbidities, including glucose hemostasis, hypertension, and dyslipidemia (p < 0.04). Moreover, the strong response subgroup had fibrosis stages F0-F2 (75.3 % vs. 56.3 %) and lower rates of advanced stages F3-F4 (24.7 % vs. 43.8 %). The F0-F2 subgroups had significantly higher rates of strong responses than the F3-F4 stages. The anti-S ≥ 200 and anti-S ≥ 400 AU/ml response achieved in 66 % and 36.8 % of the F0-F2 population was significantly higher than the 45.1 % (p = 0.006) and 23.5 % (p = 0.05) in the F3-F4 population, respectively. The Fib-4 calculations and Fibroscan evaluations were consistent with histologic fibrosis assessment. Conclusion: Advanced liver fibrosis (assessed by histology, Fib-4, or Fibroscan) is a risk factor for lower response to Pfizer's BNT162b2 vaccine, and patients should be prioritized for the vaccine booster against SARS-CoV-2.

In vivo strains at the middle and distal thirds of the tibia during exertional activities.

There is a known variance in the incidence and anatomical site of tibial stress fractures among infantry recruits and athletes who train according to established uniform training programs. To better understand the biomechanical basis for this variance, we conducted in vivo axial strain measurements using instrumented bone staples affixed in the medial cortex, aligned along the long axis of the tibia at the level of the mid and distal third of the bone in four male subjects. Strain measurements were made during treadmill walking, treadmill running, drop jumps from a 45 cm height onto a force plate and serial vertical jumps on a force plate. Significance levels for the main effects of location, type of activity and their interaction were determined by quasi-parametric methodologies. Compared to walking, running and vertical jumping peak axial tensile strain (µÎµ) was 1.94 (p = 0.009) and 3.92 times (p < 0.001) higher, respectively. Peak axial compression strain (µÎµ) values were found to be greater at the distal third than at the mid tibia for walking, running and vertical jumping (PR = 1.95, p-value<0.001). Peak axial compression and tension strains varied significantly between the subjects (all with p < 0.001), after controlling for strain gauge location and activity type. The study findings help explain the variance in the anatomical location of tibial stress fractures among participants doing the same uniform training and offers evidence of individual biomechanical susceptibility to tibial stress fracture. The study data can provide guidance when developing a generalized finite element model for mechanical tibial loading. For subject specific decisions, individualized musculoskeletal finite element models may be necessary.

Advanced Liver Fibrosis Correlates With Impaired Efficacy of Pfizer-BioNTech COVID-19 Vaccine in Medical Employees.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine has been offered to nonallergic ≥16-year-old Israeli adults since December 19, 2020. Data regarding factors associated with vaccine ineffectiveness are limited. The aim of this study is to assess the impact of hepatic fibrosis on the efficacy of the BioNTech vaccine. Serum severe acute respiratory syndrome coronavirus 2 spike immunoglobulins (S IgG) obtained at least 7 days following vaccination completion was correlated with the prevaccine calculated Fibrosis-4 (FIB-4) score among 719 employees in the Hadassah Medical Center, Jerusalem. Positive vaccine response (S IgG levels ≥ 19 AU/mL) was found in 708 of 719 individuals (98.5%). Vaccine failure (S IgG levels < 19) was found in 11 (1.5%); of these, 7 were immunosuppressed. Mean FIB-4 available in 501 of 708 vaccine responders was 1.13 ± 0.66, mean age 51.4 ± 12.4 years (29.3% males), and mean S IgG titers 239.7 ± 86.1 AU/mL. Similar to the general population, 70.5% had normal FIB-4 (<1.3), 26.8% undetermined FIB-4 (1.3-2.67), and 2.7% advanced FIB-4 (>2.67). When divided into response subgroups, 158 of 501 individuals (30.1%) with IgG titers 19-100 AU/mL had a mean FIB-4 of 1.48 ± 0.82; 198 (39.5%) with IgG titers 101-200 AU/mL had mean FIB-4 of 1.22 ± 0.76; 83 (16.6%) with titers 201-300 AU/mL had mean FIB-4 of 1.04 ± 0.48; 38 (7.6%) individuals with IgG titers 301-400 AU/ml had a mean FIB-4 of 1.08 ± 0.63; and 121 (24.2%) with IgG titers >400 AU/mL had mean FIB-4 of 1.18 ± 0.87. Increased FIB-4, age, and male gender significantly correlated with lower postvaccine IgG titers (P < 0.001). FIB-4 results were confirmed using FibroScan data displaying advanced fibrosis impact on weakened COVID-19 vaccine response. Conclusion: Immune suppression, older age, male gender, and advanced chronic liver disease are risk factors for lower vaccine response. The FIB-4 provides a simple tool to prioritize candidates for third-dose vaccine booster.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Neurotransmitters and Neuropeptides decrease PD-1 in T cells of healthy subjects and patients with hepatocellular carcinoma (HCC), and increase their proliferation and eradication of HCC cells.

T cells of aged people, and of patients with either cancer or severe infections (including COVID-19), are often exhausted, senescent and dysfunctional, leading to increased susceptibilities, complications and mortality. Neurotransmitters and Neuropeptides bind their receptors in T cells, and induce multiple beneficial T cell functions. Yet, T cells of different people vary in the expression levels of Neurotransmitter and Neuropeptide receptors, and in the magnitude of the corresponding effects. Therefore, we performed an individual-based study on T cells of 3 healthy subjects, and 3 Hepatocellular Carcinoma (HCC) patients. HCC usually develops due to chronic inflammation. The inflamed liver induces reduction and inhibition of CD4+ T cells and Natural Killer (NK) cells. Immune-based therapies for HCC are urgently needed. We tested if selected Neurotransmitters and Neuropeptides decrease the key checkpoint protein PD-1 in human T cells, and increase proliferation and killing of HCC cells. First, we confirmed human T cells express all dopamine receptors (DRs), and glutamate receptors (GluRs): AMPA-GluR3, NMDA-R and mGluR. Second, we discovered that either Dopamine, Glutamate, GnRH-II, Neuropeptide Y and/or CGRP (10nM), as well as DR and GluR agonists, induced the following effects: 1. Decreased significantly both %PD-1+ T cells and PD-1 expression level per cell (up to 60% decrease, within 1 h only); 2. Increased significantly the number of T cells that proliferated in the presence of HCC cells (up to 7 fold increase), 3. Increased significantly T cell killing of HCC cells (up to 2 fold increase). 4. Few non-conventional combinations of Neurotransmitters and Neuropeptides had surprising synergistic beneficial effects. We conclude that Dopamine, Glutamate, GnRH-II, Neuropeptide Y and CGRP, alone or in combinations, can decrease % PD-1+ T cells and PD-1 expression per cell, in T cells of both healthy subjects and HCC patients, and increase their proliferation in response to HCC cells and killing of HCC cells. Yet, testing T cells of many more cancer patients is absolutely needed. Based on these findings and previous ones, we designed a novel "Personalized Adoptive Neuro-Immunotherapy", calling for validation of safety and efficacy in clinical trials.

Randomised clinical trial: A phase 2 double-blind study of namodenoson in non-alcoholic fatty liver disease and steatohepatitis.

BACKGROUND: Namodenoson, an A3 adenosine receptor (A3AR) agonist, improved liver function/pathology in non-alcoholic steatohepatitis (NASH) preclinical models. AIM: To evaluate the efficacy and safety of namodenoson for the treatment of non-alcoholic fatty liver disease (NAFLD) with or without NASH METHODS: This phase 2 study included 60 patients with NAFLD (ALT ≥60 IU/L) who were randomised (1:1:1) to oral namodenoson 12.5 mg b.d. (n = 21), 25 mg b.d. (n = 19), or placebo (n = 20) for 12 weeks (total follow-up: 16 weeks). The main efficacy endpoint involved serum ALT after 12 weeks of treatment. RESULTS: Serum ALT decreased over time with namodenoson in a dose-dependent manner. The difference between change from baseline (CFB) for ALT in the namodenoson 25 mg b.d. arm vs placebo trended towards significance at 12 weeks (P = 0.066). Serum AST levels also decreased with namodenoson in a dose-dependent manner; at 12 weeks, the CFB for 25 mg b.d. vs placebo was significant (P = 0.03). At Week 12, 31.6% in the namodenoson 25 mg b.d. arm and 20.0% in the placebo arm achieved ALT normalisation (P = 0.405). At week 16, the respective rates were 36.8% and 10.0% (P = 0.038). A3AR expression levels were stable over time across study arms. Both doses of namodenoson were well tolerated with no drug-emergent severe adverse events, drug-drug interactions, hepatotoxicity, or deaths. Three adverse events were considered possibly related to study treatment: myalgia (12.5 mg b.d. arm), muscular weakness (25 mg b.d. arm), and headache (25 mg b.d. arm). CONCLUSION: A3AR is a valid target; namodenoson 25 mg b.d. was safe and demonstrated efficacy signals (ClinicalTrials.gov #NCT02927314).

Important relation between self-efficacy, sense of coherence, illness perceptions, depression and anxiety in patients with inflammatory bowel disease.

INTRODUCTION: Anxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease. AIMS: to investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD. PATIENTS AND METHODS: Patients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales. RESULTS: The study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn's disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014. CONCLUSIONS: Anxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients' psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

Stress assessment among internal medicine residents in a level-3 hospital versus a level-2 hospital with only emergency room service for COVID-19.

BACKGROUND: Treating COVID-19 patients can affect anxiety. OBJECTIVE: To compare the anxiety of internal medicine residents treating COVID-19 patients at a level-3 hospital with a level-2 hospital. METHODS: A questionnaire related to COVID-19 and anxiety using the State-Trait Anxiety Inventory (STAI-S) was sent to internal medicine residents of a COVID-19 referral level-3 hospital and a level-2 hospital from which all diagnosed COVID-19 cases are transferred to the COVID-19 referral hospital. RESULTS: Responses were received from 76.3% of the internal medicine residents. There was no difference in the anxiety scores between residents from the level-3 center (44.4) and the level-2 center (44.4), p = 0.9. There was a significant difference between the number of residents from the level-3 center, 22/56 (63%) and the number of residents from the level-2 center, 1/10 (10%) who were concerned about better protective gear (p = 0.003) and between residents from the level-3 center19/35 (54%) and those from the level-2 center, 1/10 (10%) who were concerned about infecting their families (p = 0.01). CONCLUSIONS: The internal medicine resident anxiety scores were not a function of hospital level, but safety was less of a concerns in the level-2 center with only emergency room COVID-19 services.

Comparison of hospital worker anxiety in COVID-19 treating and non-treating hospitals in the same city during the COVID-19 pandemic.

BACKGROUND: The Hadassah Medical Organization operates two hospitals in Jerusalem. During the COVID-19 pandemic it made an administrative decision to operate one hospital as a COVID-19 treatment hospital (CTH) and to have the second function as a non-COVID-19 treating hospital (NCTH) offering general medical services. The purpose of this study was to assess how this decision affected hospital worker anxiety. METHODS: From April 27 to May 1, during the COVID-19 pandemic in Israel, while the country was under lock-down, an electronic questionnaire survey was carried out among hospital workers of the CTH and NCTH. The questionnaire includes personal demographics and attitudes about COVID-19 and assesses present anxiety state using the State-Trait Anxiety Inventory for Adults (STAI-S) validated questionnaire. A STAI-S score of ≥45 was considered to represent clinical anxiety. RESULTS: Completed questionnaires were received from 1570 hospital employees (24%). 33.5% of responders had STAI-S scores ≥45. Multivariable regression analysis showed that being a resident doctor (odds ration [OR] 2.13; 95% CL, 1.41-3.23; P = 0.0003), age ≤ 50 (OR, 2.08; 95% Cl, 1.62-2.67; P < .0001), being a nurse (OR, 1.29; 95% CL, 1.01-1.64; P = 0.039), female gender (OR, 1.63; 95% CL, 1.25-2.13; P = 0.0003) and having risk factors for COVID-19 (OR, 1.51; 95% CL, 1.19-1.91; P = 0.0007), but not hospital workplace (p = 0.08), were associated with the presence of clinical anxiety. 69% of the responders had been tested for COVID-19, but only nine were positive. CTH workers estimated that the likelihood of their already being infected with COVID-19 to be 21.5 ± 24.7% as compared to the 15.3 ± 19.5% estimate of NCTH workers (p = 0.0001). 50% (545/1099) of the CTH workers and 51% (168/330) of the NCTH workers responded that the most important cause of their stress was a fear of infecting their families (p = 0.7). CONCLUSIONS: By multivariable analysis the creation of a NCTH during the COVID-19 pandemic was not found to be associated with a decrease in the number of hospital workers with clinical anxiety. Hospital worker support resources can be focused on the at-risk groups identified in this study.

Sense of coherence in people with and without inflammatory bowel diseases - is there a difference?

BACKGROUND AND AIMS: Sense of coherence (SOC) is a theoretical concept reflecting a person's resources and orientation, which enable individuals to cope with stressors in a health-promoting manner. In several multifactorial chronic diseases, such as diabetes mellitus and systemic lupus erythematosus, SOC was correlated with disease development. It was also related with the emotional distress in patients with inflammatory bowel disease (IBD).The aim of this study was to investigate the possible correlation between low SOC scores and the presence of IBD. METHODS: A total of 183 Crohn's disease (CD) and 71 ulcerative colitis (UC) patients completed questionnaires including demographic data and the 13 items for the SOC questionnaire. The IBD patients were matched to 124 healthy people according to age, gender, education, employment status and marital status. RESULTS: In the CD cohort, 96 patients were matched to the healthy cohort according to the propensity score value, and in the UC cohort 57 were matched. Patients with Crohns' disease had a median SOC score of 63 (IQR 56-71), and healthy matching controls of 62.5 (IQR 55.25- 68.75) p=0.369. Patients with ulcerative patients had a median SOC score of 66 (IQR 56-73) and healthy controls 62 (IQR 55-69) p=0.354. CONCLUSIONS: In our study SOC was not related to the development of IBD. The question of whether SOC is associated with the development of chronic disease and particularly with IBD remains open.