Switching from Intravenous to Subcutaneous Biological Therapy for Inflammatory Bowel Disease Patients Remains a Challenge.

Biological inflammatory bowel disease (IBD) medications, once limited to intravenous (IV) administration, can now be administered both via IV and subcutaneously (SC). This study investigates patient preferences, willingness to switch from IV to SC, and associated factors. A questionnaire covering demographics, disease-related inquiries, quality of life, and IBD medication preferences was distributed via email, the Israeli Crohn's Disease and Ulcerative Colitis Foundation, infusion centers, and clinics. From 454 IBD patients (median age: 42 years; 55.7% female), responses revealed a preference for SC every 8 weeks, which is comparable to daily oral dosing. Both options were significantly favored over IV every 8 weeks and SC every 2 weeks, with no statistically significant differences between the latter two. However, among patients who were experienced with both SC and IV administration, a clear preference for SC administration every 2 weeks over IV every 8 weeks surfaced. Among IV-treated patients, 54.5% resisted switching to SC. Key reasons for this included medical staff presence (57.7%), a fear of needles (46.4%), belief in infusion efficacy (37.1%), and longer intervals between infusions (36.1%). Findings suggest that transitioning from IV to SC treatment is challenging due to patient resistance, which is influenced by specific factors. Identifying and addressing these obstacles is crucial for optimizing IBD management.

Esophagogastroduodenal Findings in Patients with Intraductal Papillary Mucinous Neoplasms.

The association between intraductal papillary mucinous neoplasms (IPMNs) and extra-pancreatic malignancies is controversial. This cross-sectional study compared esophagogastroduodenal findings in 340 IPMN patients to those of age- and gender-matched controls without known IPMNs who underwent esophagogastroduodenoscopies (EGDs) for similar clinical reasons. The presence of gastric and esophageal cancer, Barrett's esophagus, neuroendocrine tumors (NETs), gastrointestinal stromal tumors (GISTs), gastric adenomas, and ampullary tumors was assessed. The results showed that 4/340 (1.2%) of the IPMN patients had gastric cancer and 1/340 (0.3%) had esophageal cancer. The matched control group had a similar incidence of gastric cancer (5/340) (1.5%), with no esophageal cancer cases (p > 0.999). The overall incidence of other esophagogastroduodenal conditions did not significantly differ between the IPMN patients and the controls. However, the incidence of gastric cancer in the IPMN patients was higher than expected based on national cancer registry data (standardized incidence ratio of 31.39; p < 0.001; CI 8.38-78.76). In conclusion, IPMN patients have a significantly higher incidence of gastric cancer compared to the general population. However, the incidence of esophagogastroduodenal findings, including gastric and esophageal cancer, is similar between IPMN patients and those who undergo an EGD for similar clinical indications. Further research is needed to determine optimal surveillance strategies for IPMN patients regarding their risk of developing gastric cancer.

Factors Associated With Adherence to a Gluten-Free Diet in Celiac Patients Diagnosed in Childhood as Compared to Adulthood.

Past studies have reported differences between pediatric and adult celiac disease patients. We aimed to compare factors associated with adherence to a gluten-free diet between these groups. An anonymous online questionnaire was sent via the Israeli Celiac Association and social networks to celiac patients. The Biagi questionnaire was used to assess dietary adherence. A total of 445 subjects participated. Mean age was 25.7 ± 17.5 years and 71.9% were female. Subjects were divided into six groups according to age at diagnosis: younger than 6 years (134 patients, 30.7%), 6-12 (79 patients, 18.1%), 12-18 (41 patients, 9.4%), 18-30 (81 patients, 18.5%), 30-45 (79 patients, 18.1%), and 45 years and above (23 patients, 5.3%). There were several significant differences between childhood- and adulthood-diagnosed patients. Pediatric patients were less likely to be noncompliant with a gluten-free diet (3.7% vs. 9.4%, p < .001). They were also more frequently followed by a gastroenterologist ( p < .001), a dietitian ( p < .001), and participated in a celiac support group ( p = .002). In logistic regression analyses, longer duration of disease was associated with poor compliance. In conclusion, pediatric-diagnosed celiac patients are more adherent to a gluten-free diet than those diagnosed in adulthood, with better social support and nutritional follow-up possibly contributing.

Severe and fatal COVID-19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes.

AIMS: Endotoxemia commonly occurs in severe and fatal COVID-19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID-19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and without T2D. MATERIALS AND METHODS: Plasma levels of total GLP-1, IL-6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non-severe and severe COVID-19. RESULTS: COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless of disease severity. Increased admission GLP-1 levels (p = 0.03) accompanied by two-fold increased PCT were found in severe as compared with non-severe patients. Moreover, GLP-1 and PCT levels were significantly increased in non-survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non-diabetic and T2D patients demonstrated a positive correlation between GLP-1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxaemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. CONCLUSIONS: The persistent joint increase of endogenous GLP-1 and PCT in severe and fatal COVID-19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP-1 may serve as a new biomarker of COVID-19 severity and fatal outcome.

Pancreatic cyst fluid glucose: a rapid on-site diagnostic test for mucinous cysts.

Background: Pancreatic cystic fluid (PCF) analysis is frequently used for cyst diagnosis with carcinoembryonic antigen (CEA) being the most accepted biomarker. Low glucose levels in PCF were previously suggested as a marker for mucinous cysts. A bed-side glucometer is a point-of care, immediate, simple, and cheap method which requires a small volume of PCF. Objectives: The aim of our study was to identify the optimal glucose cut-off level for identifying mucinous cysts, evaluate the diagnostic accuracy of glucose compared to CEA, and validate glucometry against reference laboratory biochemical analysis. Design: A single-center prospective cohort study. Methods: Consecutive patients aged 18 and older, who underwent pancreatic cyst evaluation, at the Tel Aviv Medical Center between 2016 and 2021 were analyzed. Cyst type was defined based on clinical, laboratory, and radiologic findings. Glucose was measured using laboratory biochemical analysis and two glucometers. Receiver operating characteristic analysis derived sensitivity, specificity, and accuracy were calculated and McNemar test was used to compare between methods. Results: One hundred and one PCF samples were evaluated. The areas under the receiver operating characteristics curve for identifying mucinous cysts using glucometer, glucose laboratory, and their combination were 0.88 (p < 0.001), 0.92 (p < 0.001), and 0.93 (p < 0.001), respectively. A glucose level of 87 mg/dL was identified as the optimal laboratory glucose threshold value to detect mucinous cyst with a sensitivity of 90.9%, specificity of 83.3%, and accuracy of 89.3, higher in comparison to cyst fluid CEA. Furthermore, PCF glucose levels had the strongest association with mucinous cysts. Conclusion: Our findings suggest that PCF glucose level is more accurate than CEA for the diagnosis of mucinous cysts. Glucometry glucose level assessment demonstrated an excellent correlation with laboratory glucose measurements and may become a useful diagnostic test.

Decompression Illness in a Scuba Diver With Significant Esophageal Injury.

Scuba divers are at risk of decompression illness, of which arterial gas embolism is the most feared consequence. Severe complications involving the gastrointestinal tract are rare. In this report, we describe a case of an experienced scuba diver who was forced to rapidly ascend because of a mechanical failure. His course was complicated by severe esophageal mucosal injury including multiple ulcerations. Although he improved clinically, an esophageal stricture subsequently formed, which required dilation. This seems to be the first case report of significant esophageal injury resulting from decompression illness in a scuba diver.

The Epidemiology of Multidrug-Resistant Sepsis among Chronic Hemodialysis Patients.

Sepsis is one of the leading causes of hospitalization and death among hemodialysis patients. Infections due to multidrug-resistant organisms (MDROs) are common among these patients, but empiric broad-spectrum coverage for every septic patient is associated with unfavorable outcomes. A retrospective case-control study was conducted at Shamir Medical Center, Israel (July 2016-April 2020), to determine predictors of MDRO infections among septic (per SEPSIS-3) ambulatory adult hemodialysis patients with permanent dialysis access (i.e., fistula, graft, or tunneled Perm-A-Cath). MDROs were determined according to established definitions. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prediction score and determine its performance. Of 509 patients, 225 (44%) had microbiologically confirmed infection, and 79 patients (35% of 225) had MDROs. The eventual independent predictors of MDRO infections were Perm-A-Cath access (vs. fistula or graft, aOR = 3, CI-95% = 2.1-4.2) and recent hospitalization in the previous three months (aOR = 2.3, CI-95% = 1.6-3.3). The score to predict MDRO sepsis with the highest performances contained seven parameters and displayed an area under the receiver operating characteristic curve (ROC AUC) of 0.74. This study could aid in defining a group of hemodialysis patients for which empiric broad-spectrum agents could be safely avoided.

Establishing priorities for diabetes action goals according to key opinion leaders and health professionals.

BACKGROUND: The ever-increasing burden of diabetes and the limited resources highlight the need for prioritization of national action goals for diabetes management. The Israeli National Diabetes Council (INDC) initiated a prioritization process aiming to set a top list of diabetes related goals, as suggested by decision makers and health professionals. METHODS: A 2-step prioritization process, including a small (n = 32) circle of key opinion leaders of the INDC and a larger (n = 195) nationwide circle of diabetes health professionals consisting of physicians, nurses, and dieticians working in diabetes care centers, hospitals and family practice clinics, was established. An online questionnaire presenting 45 different action areas in diabetes prevention and care was distributed to the INDC members who ranked the 3 top diabetes priorities based on their individual interpretation of importance and applicability. The 7 highest ranking priorities were later presented to hospital-based and community diabetes health professionals. These professionals selected the 3 top priorities, based on their perceived importance. RESULTS: Council members opted mostly for action areas regarding specific populations, such as clinics for adult type-1 diabetes patients, diabetic foot, and pediatric and adolescent patients, while the health professionals' top priorities were mostly in the general field of prevention, namely high-risk prediabetes population, prevention of obesity, and promotion of healthy life-style. In addition, priorities differed between hospital and community health professionals as well as between different professional groups. CONCLUSIONS: A national prioritization process of action areas in diabetes prevention and care is attainable. The resulting item list is affected by professional considerations. These priorities may direct efforts in the implementation of interventions to improve national-level diabetes management.

Increased prevalence of colorectal neoplasia in patients with intraductal papillary mucinous neoplasms.

Background: The association between intraductal papillary mucinous neoplasms (IPMNs) and colorectal cancer (CRC) and polyps is controversial. Objectives: To compare the prevalence of CRC and colorectal polyps among patients with IPMN and matched average risk individuals. Methods: A match cross-sectional historical study comparing colonoscopy findings of 310 patients with IPMN cysts who underwent at least one colonoscopy examination from 2004 through 2019, with 310 age- and gender-matched average risk participants who underwent a screening colonoscopy. CRC and polyps were assessed in both groups. The prevalence and odds ratio were calculated. Results: CRC was diagnosed in 16 of 310 patients with IPMN (5.2%), and at least one polyp was detected in 96 patients (31%). The prevalence of CRC was greater among patients with IPMN than in matched individuals [5.2% versus 1.3%, p = 0.012, prevalence odds ratio (POR) 4, confidence interval (CI) 1.29-16.44]. The overall prevalence of polyps was not higher among patients with IPMN than in matched individuals (31% versus 26.8%, p = 0.291, POR 1.22, CI 0.85-1.76). However, the prevalence of colorectal adenomas with high-grade dysplasia was higher in patients with IPMN than in matched individuals (4.2% versus 1%, p = 0.02, POR 4.33, CI, 1.19-23.7). The prevalence of large polyps (i.e. more than 20 mm in size) was also greater in patients with IPMN than in matched individuals (6.1% versus 1.9%, p = 0.011, POR 3.6, CI, 1.29-12.40). Conclusion: Patients with IPMN have a significantly higher prevalence of CRC and advanced polyps than the average risk population. In view of our findings, we suggest that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken.

The effect of direct-acting antiviral regimens and telemedicine on the treatment of inmates with hepatitis C virus infection in Israeli prisons.

BACKGROUND: Direct-acting antiviral (DAA) regimens and telemedicine services are both options for treating hepatitis C virus (HCV) within the prison setting. We aimed to compare factors associated with HCV treatment success over the past decade in Israeli prisons, specifically the influence of DAAs and telemedicine. METHODS: We retrospectively reviewed the medical records of inmates with HCV infection in Israeli prisons from 2010 through 2020. Demographic, clinical, and laboratory data were recorded, including treatment regimens and success rates. RESULTS: A total of 273 inmates were treated; mean age 45 ± 9.36 years; 98.2% males; 63.9% with a history of drug abuse. Advanced fibrosis was documented in 42.9%. The most common genotypes were 1 (46%) followed by 3 (40.7%). Interferon-based regimens were given to 68 inmates between 2010 and 2017. DAA agents were introduced in 2016, with pan-genotype regimens being exclusively used since 2019. Telemedicine services were used in 140 patients (51.3%), starting in February 2019. The sustained viral response (SVR) rate with interferon-based therapy was 78.8% and 98.8% with DAA treatment, giving an overall SVR of 93.2%. This difference between regimens proved to be the only statistically significant predictor of treatment success. The number of prisoners being treated with DAAs increased exponentially after telemedicine was introduced. Comparable SVR rates were achieved with either in-person or telemedicine consultation. CONCLUSION: Screening of this high-risk population and using telemedicine for treatment may be an effective strategy for the elimination of HCV from the prison population.

Indwelling Urinary Catheter and Dementia Are Associated with Enterococcal Urinary Tract Infections in Hospitalized Patients.

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.

The First Fatal Post-COVID-19 Adult Patient with Multi-System Inflammatory Syndrome in Israel.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series.

Hyper-Activation of Endogenous GLP-1 System to Gram-negative Sepsis Is Associated With Early Innate Immune Response and Modulated by Diabetes.

BACKGROUND: Culture-positive gram-negative sepsis induces greater magnitude of early innate immunity /inflammatory response compared with culture-negative sepsis. We previously demonstrated increased activation of anti-inflammatory Glucagon Like Peptide-1 (GLP-1) hormone in initial phase of sepsis more pronounced in diabetes patients. However, whether GLP-1 system is hyperactivated during the early innate immune response to gram-negative sepsis and modulated by diabetes remains unknown. OBJECTIVES: Total and active GLP-1, soluble Dipeptidyl peptidase 4 (sDPP-4) enzyme, and innate immunity markers presepsin (sCD14) and procalcitonin (PCT) in plasma were determined by ELISA on admission and after 2 to 4 days in 37 adult patients with and without type 2 diabetes and gram-negative or culture-negative sepsis of different severity. RESULTS: Severe but not non-severe sepsis was associated with markedly increased GLP-1 system response, which correlated with PCT and the organ dysfunction marker lactate. Culture-positive gram-negative bacteria but not culture-negative sepsis induced hyper-activation of GLP-1 system, which correlated with increased innate immune markers sCD14, PCT, and lactate. GLP-1 inhibitory enzyme sDPP-4 was down regulated by sepsis and correlated negatively with sCD14 in gram-negative sepsis. Diabetic patients demonstrated increased GLP-1 response but significantly weaker innate immune response to severe and gram-negative sepsis. CONCLUSIONS: Early stage of gram-negative sepsis is characterized by endogenous GLP-1 system hyperactivity associated with over activation of innate immune response and organ dysfunction, which are modulated by diabetes. Total GLP-1 may be novel marker for rapid diagnosis of gram-negative sepsis and its severity.

Chairing the internal medicine department- analysis of current state and future trends in Israel.

BACKGROUND: Professional skills and academic records of the highest degree are essential requirements for the chairmanship of internal medicine departments. Whether the new generation and future successors of Israeli chairmen is endowed with these attributes is not known. PURPOSE: To determine whether there is a lack of future suitable successors for the current heads of internal medicine departments in Israel and to compare the demographic, academic and professional characteristics of the older and newer generations of department heads. METHODS: An online anonymous questionnaire was nationally distributed during 2016 to all active heads of internal medicine departments in Israel (n = 101). First round was followed by two runs of personal phone calls to promote participation. RESULTS: Sixty-seven (67%) of chairmen responded. The vast majority of current chairs of internal medicine departments are males (N = 59, 88%) over 50 years of age (N = 58, 86%) with established academic background with lecturer degree or higher (N = 57, 85%). Only 19 (28%) of current heads assigned a future successor. Comparison of chairmen who did and did not assigned successors demonstrated that assignment of successors was associated with higher academic status (P < 0.02) and longer chairmanship (p < 0.01) but not with mean age of current chairmen (p < 0.08). Nevertheless, most assignments (55%) were done by chairmen in the 61 to 67 years age group. As compared to current chairmen, the designated successors have lesser academic status (p < 0.01) and are characterized by a higher female prevalence (P < 0.03). CONCLUSIONS: Significant demographic, professional and academic differences exist between the current chairs of internal medicine departments in Israeli hospitals and their future successors. This underscores the need for reassessment of the availability and requirements of this crucial position.

Postoperative Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery Predicts Long-Term Atrial Fibrillation and Stroke.

BACKGROUND: Atrial fibrillation (AF) is a common complication of coronary artery bypass graft (CABG) surgery, occurring in 20%-40% of patients, mostly during the first week after surgery. It is associated with increased morbidity and mortality, but data are limited. OBJECTIVES: To assess the correlation between new-onset in-hospital AF following CABG and long-term AF, cerebrovascular accident (CVA), or death. METHODS: We conducted an analysis of 161 consecutive patients who underwent isolated CABG surgery in a tertiary center during the period 2002-2003. RESULTS: Patients' mean age was 72 years, and the majority were males (77%). Approximately half of the patients experienced prior myocardial infarction, and 14% had left ventricular ejection fraction < 40%. Postoperative AF (POAF) occurred in 27% of the patients. Patients were older and had larger left atrium diameter. POAF was strongly correlated with late AF (OR 4.34, 95%CI 1.44-13.1, P = 0.01) during a mean follow-up of 8.5 years. It was also correlated with long-term stroke but was not associated with long-term mortality. CONCLUSIONS: POAF is a common complication of CABG surgery, which is correlated with late AF and stroke. Patients with POAF should be closely monitored to facilitate early administration of anticoagulant therapy in a high risk population upon recurrence of AF.