Residence in Peripheral Regions and Low Socioeconomic Status Are Associated With Worse Outcomes of Inflammatory Bowel Diseases: A Nationwide Study From the epi-IIRN.

BACKGROUND: Timely access to quality medical care impacts patient outcomes in inflammatory bowel disease (IBD). In a nationwide study from the epidemiology group of the Israeli IBD research nucleus we aimed to assess the impact of residence and socioeconomic status (SES) on disease outcomes. METHODS: We utilized data from the 4 health maintenance organizations in Israel, representing 98% of the population. Regions were defined as central, northern and southern; SES was graded from lowest to highest (from 1 to 4) as per Israel Central Bureau of Statistics. The primary outcome was steroid dependency, with secondary outcomes of surgeries and biologic therapy use. RESULTS: A total of 28 216 IBD patients were included: 15 818 (56%) Crohn's disease (CD) and 12 398 (44%) ulcerative colitis; 74%, 12% and 14% resided in central, southern, and northern Israel, respectively (SES 1: 21%, SES 4: 12%). Lower SES was associated with steroid dependency (20% in SES 1 vs 12% in SES 4 in CD; P < .001; and 18% vs 12% in ulcerative colitis; P < .001), and higher surgery rates (12% vs 7%; P < .001, and 1.4% vs 0.7%; P = .115, respectively). There were higher steroid dependency and CD surgery rates in peripheral vs central regions. In multivariable models, both SES and peripheral region were independently associated with poorer outcomes. CONCLUSIONS: We found that lower SES and peripheral residence were associated with deleterious outcomes in IBD. This should be considered by policymakers and should encourage strategies for improving outcomes in populations at risk.

In a novel nationwide population study, we found that patients with inflammatory bowel disease living in peripheral regions and those with lower socioeconomic status had significantly worse inflammatory bowel disease outcomes, notably higher corticosteroid dependency, higher surgery rate, and higher repeat surgery rate.

Diagnostic Value of High-Sensitivity Cardiac Troponin-I in Patients After Out-of-Hospital Cardiac Arrest.

Knowing the etiology of cardiac arrest (CA) is important for treatment decisions. Results of previous studies on the diagnostic role of cardiac troponin in patients resuscitated from CA are controversial, few studies were done during the era of high-sensitivity cardiac troponin-I (hs-cTnI), and kinetics of hs-cTnI was not thoroughly investigated. We aimed to explore the diagnostic value of hs-cTnI in patients resuscitated from out-of-hospital CA (OHCA). This retrospective study included 201 consecutive patients after OHCA admitted to the intensive cardiac care unit at Rambam Health Care Campus from 2016 to 2021. Patients were divided into 2 groups according to etiology of CA: group 1-patients with definite acute myocardial infarction (AMI), group 2-patients in whom AMI was excluded. Values of hs-cTnI on admission, peak hs-cTnI, and hs-cTnI upslope were compared between patients with AMI and non-AMI. Peak hs-cTnI and hs-cTnI upslope differed significantly between patients with non-AMI versus AMI CA (median 1,424 vs 32,558 ng/L, p <0.0001 and median 109 vs 2,322 ng/L/h, p <0.0001, respectively). Moreover, peak hs-cTnI and hs-cTnI upslope were found to have good discrimination performance between patients with non-AMI and AMI, with area under the curve receiver operating characteristics (ROC) curves of 0.83 and 0.80, respectively. In conclusion, in patients resuscitated from OHCA values of peak hs-cTnI and hs-cTnI upslope could be helpful in the diagnosis of etiology of CA as adjunct to other diagnostic methods.

The Long-Term Outcome of Kidney Transplant Recipients in the Eighth Decade Compared With Recipients in the Seventh Decade of Life.

BACKGROUND: With the aging of the population, more older patients are being considered for kidney transplantation; therefore, it is crucial to evaluate the risks and benefits of transplantation in this population. This study aimed to assess long-term outcomes of kidney transplantation in a cohort of patients who underwent kidney transplantation at age >70 years, compared with patients aged 60 to 69 years at transplantation. METHODS: Included in the study were 261 consecutive kidney transplant recipients: 52 were aged >70 years, and 209 were aged 60 to 69 years at transplantation. Data were collected retrospectively and analyzed using multivariate logistic regression to identify potential outcome risk factors. RESULTS: The number of transplants in both groups increased during the study period. Mortality after transplantation was strongly correlated to age (hazard ratio [HR] = 1.11; 95% CI, 1.05-1.18; P < .001), deceased donor (HR = 2.0; 95% CI, 1.1-3.8; P = .034), and pretransplant diabetes (HR = 2.9; 95% CI, 1.7-4.9; P = .001). Recipients aged >70 years had an increased risk of death censored graft failure (HR = 2.98; 95% CI, 1.56-5.74; P = .001). In living donor transplants, 3-year survival was 80% in recipients age >70 years, compared with 98% in the 60- to 69-year group. Five-year survival was 71% and 92%, respectively. In deceased donor transplants, 3-year survival was 63% and 78%, and 5-year survival was 58% and 72%, respectively. The risk of malignancy (excluding nonmelanotic skin cancer) was nearly triple in the age >70 years group (HR = 2.96; 95% CI, 1.3-6.8; P = .01). CONCLUSIONS: Patient and graft survival in kidney recipients in the eighth decade is worse compared with recipients in the seventh decade of life. However, it is improved with living kidney donation.

Electrolyte Imbalance in Anti-LGI1 Encephalitis: It Is Not All in Your Head.

BACKGROUND AND OBJECTIVES: Antileucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis was first described in 2010 and is today the most common type of limbic encephalitis. During the course of the disease, 60%-88% of the patients develop hyponatremia. The etiology of the sodium disorder is unclear, often presumed to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Other electrolyte abnormalities have not been reported in association with anti-LGI1 antibody encephalitis. Due to the presence of hypomagnesemia and hypophosphatemia in our patients, we set out to try to find the expression of LGI1 protein in the kidney as an explanation for these abnormalities. METHODS: We reviewed the medical files of all patients diagnosed with anti-LGI1 antibody encephalitis, at the Department of Neurology in the Tel Aviv Medical Center between January 2011 and December 2020, exploring for electrolyte abnormalities. Using tissue staining, Western blot, mass spectrometry, and RNA expression techniques, we tried to demonstrate the expression of LGI1 protein in the human kidney. RESULTS: We identified 15 patients diagnosed with anti-LGI1 antibody encephalitis. Their average age was 65 years (44-80), and 9 were male individuals. Thirteen of the 15 patients (87%) developed varying degrees of hyponatremia. Laboratory studies demonstrated low serum osmolality, low serum blood urea nitrogen, and low uric acid, with a high urinary sodium and inappropriately high urine osmolality, supporting the presumable diagnosis of SIADH. One patient with hyponatremia that was tested, had high levels of copeptin, supporting the diagnosis of SIADH. In addition to hyponatremia, 7 patients (47%) exhibited other electrolyte abnormalities; 5 patients (33%) had overt hypophosphatemia, 4 patients (27%) had overt hypomagnesemia, and 2 other patients (13%) had borderline low magnesium levels. Western blot analysis of human kidney lysate, mass spectrometry, and qRT-PCR failed to demonstrate the expression of LGI1 protein in the kidney. DISCUSSION: Hyponatremia in patients with anti-LGI1 antibody encephalitis is due to SIADH as previously assumed. Other electrolyte abnormalities such as hypomagnesemia and hypophosphatemia occur in at least 40% of patients and may be another clue for the diagnosis of anti-LGI1 antibody encephalitis. Because we failed to demonstrate LGI1 expression in the kidney, the results of our study suggest that renal losses lead to these disturbances, most probably due to SIADH.

Renal Tubular CD24 Upregulation Aggravates Folic Acid Induced Acute Kidney Injury: A Possible Role for T Regulatory Cells Inhibition in Mice.

Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24-/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24-/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24-/- FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI.

Ethnic Issues and Disparities in Inflammatory Bowel Diseases: What Can We Learn from the Arab Population in Israel?

Inflammatory bowel diseases are increasing among different ethnic groups. We aimed to compare the clinical characteristics, complications, and outcomes among Arab and Jewish people sharing the same healthcare system. All patients older than 18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between the years 2000 and 2021 were included. Data regarding demographics, disease characteristics, extraintestinal manifestation, treatment, comorbidities, and mortality were retrieved. A total of 1263 (9.8%) Arab CD patients were compared with 11,625 Jewish CD patients, and 1461 (11.8%) Arab UC patients were compared to 10,920 Jewish patients. Arab CD patients were younger at diagnosis, 36.11 ± 16.7 compared to 39.98 ± 19.4 years, p < 0.001, 59.5% males compared to 48.7%, p < 0.001; in addition, Arab CD patients had a higher rate of anal fissure, perianal abscess, erythema nodosum, diabetes mellitus, obesity, liver cirrhosis, and male infertility. Arab CD patients were less frequently treated with azathioprine or mercaptopurine compared with Jewish patients. No significant difference was found in the rate of anti-TNF treatment, but a higher rate of steroids treatment was found. The all-cause mortality of CD patients was lower among Arab patients (8.4% vs. 10.2%, p = 0.039). Significant differences were found regarding disease characteristics, course, comorbidities, and treatment among Arab and Jewish patients with IBD.

Randomised clinical trial: Psychological intervention improves work productivity and daily activity by reducing abdominal pain and fatigue in Crohn's disease.

BACKGROUND: Chronic abdominal pain and fatigue are characteristics of Crohn's disease (CD) and contribute to functional impairments. AIMS: To examine whether CD-tailored cognitive-behavioural and mindfulness intervention (COBMINDEX) is effective in reducing abdominal pain and fatigue in patients with CD and whether changes in abdominal pain and fatigue mediate any beneficial effects of COBMINDEX on impairments in work productivity and daily activities. METHODS: This is a secondary analysis of a parallel-group multicentre randomised controlled trial. Patients with mild-to-moderate CD (n = 142) were randomised into either intervention group receiving COBMINDEX, or control group receiving treatment-as-usual for 3 months followed by COBMINDEX. Complete data were collected from 120 patients (34.0 ± 10.7 years, 62.5% female, intervention = 60, control = 60). Analysis of covariance assessed group differences in 3-month follow-up scores, controlling for baseline scores. Multiple parallel mediation analysis assessed the proposed mechanisms for the entire sample. RESULTS: The intervention group demonstrated significantly lower levels of abdominal pain (F = 17.46, p < 0.001, η2 p  = 0.13), fatigue (F = 7.26, p = 0.008, η2 p  = 0.06) and impairments at work (F = 4.82, p = 0.032, η2 p  = 0.07) and daily activities (F = 6.26, p = 0.014, η2 p  = 0.05), compared with treatment-as-usual. Moreover, changes in abdominal pain and fatigue significantly mediated the beneficial effects of COBMINDEX on patients' work productivity (b = -9.90, SE = 2.86, 95% CI: -16.11 to -4.94) and daily activities (b = -9.65, SE = 1.91, 95% CI: -13.77 to 6.35), independent of changes in disease activity. CONCLUSIONS: COBMINDEX is effective at reducing abdominal pain and fatigue in patients with CD, which in turn leads to improvement in functioning. Clinicians should incorporate screening for severe abdominal pain and fatigue and consider offering cognitive-behavioural and mindfulness training. CLINICALTRIALS: gov, Number: NCT05085925. Ministry of Health in Israel (https://my.health.gov.il/CliniTrials/Pages/MOH_2020-02-24_008721.aspx).

The impact of the COVID-19 pandemic on colorectal and gastric cancer diagnosis, disease stage and mortality.

Background: Since the outbreak of COVID-19, a significant decline in endoscopic procedures has been observed. Aims: We investigated the change of incidence, clinical characteristics, disease stage and mortality of patients with gastric cancer (GC) or colorectal cancer (CRC) diagnosed in 2020 compared to the pre-pandemic year 2019. Methods: Demographic, clinical and laboratory data on all patients diagnosed with GC or CRC at the Soroka University Medical Center were retrospectively collected and compared. Number of cases, time of diagnosis, clinical presentation, staging at diagnosis and mortality rates were compared. Results: Two hundred sixteen patients were diagnosed with CRC in 2019, whereas only 162 were diagnosed in 2020 (25% reduction), while 36 GC diagnoses were made in 2019 compared to 24 in 2020 (33% reduction). The age-adjusted incidence was calculated to be 24.28 for CRC and 5.0 for GC in 2020 compared to 29.93 and 5.32 in 2019, respectively. CRC patients had a significantly lower rate of rectal bleeding as their presenting symptom in 2020 compared with 2019, 8.1 vs. 19% (p = 0.003), but higher rate of diarrhea as their presenting symptom, 4.3 vs. 1% (p = 0.044). No significant differences regarding other presenting symptoms, comorbidities, surgery or mortality rates were found between the groups diagnosed in 2019 or 2020. Conclusion: A decrease in GC and CRC incidence was observed during the year 2020; lower rate of rectal bleeding and higher rate of diarrhea as presenting symptoms were noted in 2020, but no significant difference was found regarding other presenting symptoms, disease stage, surgery or mortality.

Nonalcoholic Fatty Liver Disease before Kidney Transplantation Correlates with New Onset Diabetes and Poor Metabolic Outcomes.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality after kidney transplantation. Metabolic syndrome is common in renal transplant recipients and is associated with increased CVD risk in those patients. Nonalcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of a multi-system disorder, including CVD and metabolic syndrome. The data about prevalence of NAFLD before kidney transplantation and its consequences following transplantation are scarce. METHODS: A retrospective study of metabolic parameters and sonographic evidence of NAFLD, and an analysis of its metabolic outcomes, was performed in 341 consecutive kidney transplant recipients. RESULTS: One-hundred twenty-four (36.4%) kidney recipients had NAFLD before transplantation. The risk of NAFLD before kidney transplantation was independently and significantly related to diabetes (OR = 1.8), male gender (OR = 1.4), older age (every year of age increased the risk by 4%), higher BMI (every increase of 1 kg/m2 increased the risk by 15%), and higher triglycerides level. Mean levels of liver enzymes were similar in patients with and without NAFLD. Recipients with NAFLD before transplantation had a higher prevalence of new onset diabetes, even after adjustment to covariables. In addition, they had a higher increase in liver enzymes, triglycerides, and FIB-4 score, as an indication of liver fibrosis, after transplantation. Furthermore, NAFLD pre-transplantation was independently associated with cardiovascular mortality (HR = 4.4) following kidney transplantation. CONCLUSIONS: Sonographic evidence of NAFLD before kidney transplantation is associated with significant metabolic outcomes including de novo diabetes and cardiovascular mortality following transplantation and should be included as part of the assessment of kidney transplant candidate.

Presence of Sarcopenia before Kidney Transplantation Is Associated with Poor Outcomes.

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with renal failure. It is crucial to select which patients may benefit from renal transplantation and which are at high risk for post-transplant complications. Sarcopenia is associated with poor outcome in various conditions, including in chronic kidney disease patients. The gold standard for measuring sarcopenia is computed tomography (CT) imaging to estimate muscle mass and quality since it is objective, reproducible, and reflects the overall health condition. The data regarding those measurements among kidney transplant recipients are limited, therefore we aimed to describe it in patients before kidney transplantation, assess the parameters associated with sarcopenia, and evaluate the clinical significance of those markers on outcomes following transplantation. METHODS: We retrospectively analyzed 183 kidney transplant recipients who had a CT scan 90 days prior to transplant. Sarcopenia was assessed by measuring the cross-sectional area (CSA) and mean muscle density of the psoas muscle at the third and fourth lumbar vertebrae levels and paravertebral muscles at the 12th thoracic vertebra level. RESULTS: There was a strong linear correlation between muscle size measured as CSA of the psoas muscle at the L3 and L4 vertebral body level and the CSA of the paravertebral muscles at the D12 vertebra level, and a moderate correlation to muscle density at those levels. Age was independently associated with risk of sarcopenia, defined as psoas CSA in the lowest tertile, with every year of age increasing the risk by 5%. CSA at the L3 level had a significant independent association with post kidney transplantation mortality, with an adjusted hazard ratio of 0.86 per cm2. There was a significantly longer hospitalization period postoperation in kidney recipients in the lower tertile of psoas CSA and density. CONCLUSIONS: Sarcopenia as measured by psoas CSA is associated with poor short- and long-term outcomes following kidney transplantation and should be included as part of the assessment of kidney transplantation candidates.

Humoral Response to the Third Dose of Sars-Cov-2 Vaccine in Kidney Transplant Recipients.

BACKGROUND: Most solid organ transplant recipients did not develop an appreciable serologic response after 2 doses of the mRNA SARS-CoV-2 vaccine. METHODS: We analyzed the humoral response after a third dose of the BNT162b2 vaccine in 130 kidney transplant recipients, compared to 48 health care workers, and associated factors, including prevaccine cellular immune response, by evaluating intracellular cytokine production after stimulation of donor's peripheral blood mononuclear cells. RESULTS: After 2 doses, most of the controls (47 out of 48, 98%) and only 40% of kidney recipients (52 of 130) kidney recipients were seropositive (P < .001). Most seronegative recipients developed a serologic response after the booster (47 out 78, 60%), thus bringing the total number of seropositive recipients to 99 out of 130 (76%). After the third dose, there was a significant increase in antibodies titers in both groups. Decreased humoral response was significantly associated with an older age, lower lymphocyte count, and a lower level of antibodies before booster administration. CD4+TNFα+ and CD4+INFγ+ were correlated with mean increase in antibody titers. CONCLUSIONS: A third dose of the BNT162b2 mRNA vaccine in kidney recipients is safe and effectively results in increased IgG anti-S levels, including in individuals who were seronegative after 2 doses. Long-term studies of the length of the immune response and protection are required.

Corticosteroids and Mesalamine Versus Corticosteroids for Acute Severe Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.

PTH-Induced Bone Regeneration and Vascular Modulation Are Both Dependent on Endothelial Signaling.

The use of a bone allograft presents a promising approach for healing nonunion fractures. We have previously reported that parathyroid hormone (PTH) therapy induced allograft integration while modulating angiogenesis at the allograft proximity. Here, we hypothesize that PTH-induced vascular modulation and the osteogenic effect of PTH are both dependent on endothelial PTH receptor-1 (PTHR1) signaling. To evaluate our hypothesis, we used multiple transgenic mouse lines, and their wild-type counterparts as a control. In addition to endothelial-specific PTHR1 knock-out mice, we used mice in which PTHR1 was engineered to be constitutively active in collagen-1α+ osteoblasts, to assess the effect of PTH signaling activation exclusively in osteoprogenitors. To characterize resident cell recruitment and osteogenic activity, mice in which the Luciferase reporter gene is expressed under the Osteocalcin promoter (Oc-Luc) were used. Mice were implanted with calvarial allografts and treated with either PTH or PBS. A micro-computed tomography-based structural analysis indicated that the induction of bone formation by PTH, as observed in wild-type animals, was not maintained when PTHR1 was removed from endothelial cells. Furthermore, the induction of PTH signaling exclusively in osteoblasts resulted in significantly less bone formation compared to systemic PTH treatment, and significantly less osteogenic activity was measured by bioluminescence imaging of the Oc-Luc mice. Deletion of the endothelial PTHR1 significantly decreased the PTH-induced formation of narrow blood vessels, formerly demonstrated in wild-type mice. However, the exclusive activation of PTH signaling in osteoblasts was sufficient to re-establish the observed PTH effect. Collectively, our results show that endothelial PTHR1 signaling plays a key role in PTH-induced osteogenesis and has implications in angiogenesis.

Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the hypothalamus-pituitary-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) impacts their inflammatory process. METHODS: Circulating inflammatory markers and a wide range of psychological parameters related to stress and well-being were measured in CD patients before and after COBMINDEX. Inflammatory markers in CD patients were also compared to age- and sex-matched healthy controls (HCs). RESULTS: CD patients exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by interconnected inflammatory modules represented by IL-6, TNFα, IL-17, MCP-1 and IL-18. Notably, higher IL-18 levels correlated with higher score of stress and a lower score of wellbeing in CD patients. COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 and IFNα and negatively with those of MCP-1. Furthermore, inflammatory markers of CD patients at baseline predicted COBMINDEX efficacy, as higher levels of distinct cytokines and cortisol at baseline, correlated negatively with changes in disease activity (by Harvey-Bradshaw Index) and psychological distress (global severity index measure) following COBMINDEX. CONCLUSION: CD patients have a characteristic immunological profile that correlates with psychological stress, and disease severity. We suggest that COBMINDEX induces stress resilience in CD patients, which impacts their well-being, and their disease-associated inflammatory process.

Randomized Controlled Trial of Cognitive-Behavioral and Mindfulness-Based Stress Reduction on the Quality of Life of Patients With Crohn Disease.

BACKGROUND: Patients with Crohn disease have debilitating psychological symptoms, mental fatigue, and poor quality of life. Psychological intervention may improve these symptoms. METHODS: We performed a randomized parallel-group physician-blinded trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) on quality of life and psychological symptoms in adults with mild-moderate Crohn disease. COBMINDEX was taught by social workers in one-on-one video conferences over 3 months; quotidian home practice was mandated. RESULTS: Fifty-five COBMINDEX and 61 waitlist control patients completed the study; mean age was 33 years and 65% of participants were women. At 3 months, COBMINDEX patients had significantly reduced disease activity (per Harvey-Bradshaw Index score, C-reactive protein level, and calprotectin level), increased quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] score increased from baseline 41 to 50; P < 0.001), decreased psychological symptoms (Global Severity Index [GSI], 0.98-0.70; P < 0.001), reduced fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue, 26-33; P < 0.001), and increased mindfulness disposition (Freiburg Mindfulness Inventory, 33-38; P < 0.001). Waitlist patients had a significant but small change in Harvey-Bradshaw Index, SIBDQ, and GSI scores, without improvement in fatigue or mindfulness. There were significant correlations (0.02 > P < 0.002) in COBMINDEX patients between baseline SIBDQ, GSI, Freiburg Mindfulness Inventory, and Functional Assessment of Chronic Illness Therapy-Fatigue scores with a relative change (baseline to 3 months) of the SIBDQ score, but none among waitlist patients. Predictors of relative change of the SIBDQ score in COBMINDEX patients included the GSI score (90% quantile; coefficient 0.52; P < 0.001), somatization (90%; 0.20; P = 0.001), depression (75%; 0.16; P = 0.03), and phobic anxiety (75%; 0.31; P = 0.008). CONCLUSIONS: COBMINDEX was effective in increasing patients' quality of life and reducing psychological symptoms and fatigue. Patients with severe baseline psychological symptoms benefited the most from COBMINDEX.

Improved Outcomes of Paediatric and Adult Crohn's Disease and Association With Emerging Use of Biologics-A Nationwide Study From the Epi-IIRN.

BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; p < 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.

Normative data for the Brief Symptom Inventory for patients with Crohn's disease.

OBJECTIVE: The Brief Symptom Inventory (BSI) is a self-report measure of psychological symptoms in clinical and non-clinical populations. However, norms for BSI are lacking for patients with chronic illness, such as Crohn's disease (CD). This study aimed to provide BSI clinical norms using a cohort of CD patients. DESIGN: Adult Israeli CD patients (n = 430) completed questionnaires regarding clinical, demographic and psychological aspects of disease, including BSI. Their BSI data were compared with published norms from adult Israeli population and British psychiatric outpatients. RESULTS: CD patients in active disease state had higher levels of mental health symptoms than those in remission. Interestingly, levels of symptomatology did not differ with respect to disease duration. No significant sex differences in BSI dimensions were found, with the exception of somatization. Being younger than 60 years and having lower economic status were associated with more severe psychological symptoms. Psychological symptom levels in CD patients were high in comparison to the Israeli general population, but low compared to British psychiatric outpatients. CONCLUSION: Results confirm the link between CD and elevated psychological symptoms. The findings highlight the need to use appropriate BSI norms when assessing clinically significant levels of psychological symptoms in non-psychiatric patients with chronic illness.

Less Emergency Department Abdominopelvic Computed Tomography for Patients With Crohn's Disease: A New Scoring System.

BACKGROUND: In recent years, the use of abdominal pelvic computed tomography (APCT) in the emergency department (ED) for patients with Crohn's disease (CD) has risen steadily. Thus, exposing these patients to recurrent radiation, despite studies showing that only 30% to 40% had significant findings in ED APCT. GOAL: Our aim was to find clinical and laboratory variables that can predict substantial findings on ED APCT, which may require invasive intervention. METHODS: We analyzed ED visits of patients with known CD that underwent an emergent APCT for gastrointestinal complaints, over a 10-year period. Patients with positive and negative findings in the APCT were compared in order to evaluate independent effects of different variables, including patients' characteristics, CD history, ED complaints, and laboratory tests. RESULTS: In 44% of 183 ED visits, there were significant findings on ED APCT, however, only 22% of them underwent invasive intervention. Laboratory tests: C-reactive protein >50 mg/L, neutrophil count >75%, platelet count >350×10 9 /L, and ileocolon location at diagnosis were all positive predicting factors. Whereas, smoking or ED complaints of diarrhea/fever reduced the risk for significant findings. CONCLUSIONS: Using the 7 most significant predicting factors, we built an easy to use scoring system-Crohn Assessment Tool for CT upon Hospitalization (CATCH) for ED clinicians. This scoring system could have prevented unnecessary ED APCT from 42% of the patients in our study, without missing those who required invasive intervention.

Colectomy Rates did not Decrease in Paediatric- and Adult-Onset Ulcerative Colitis During the Biologics Era: A Nationwide Study From the epi-IIRN.

BACKGROUND: It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. METHODS: Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan-Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. RESULTS: A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8-9.1] in 2005-2008 vs 0.8 years [0.4-1.5] in 2015-2018; p < 0.001]. Annual rates of surgeries [AAPC -1.3; p = 0.6] and steroid-dependency [AAPC -1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC -1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. CONCLUSION: During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.

Kidney transplant recipients vaccinated before transplantation maintain superior humoral response to SARS-CoV-2 vaccine.

Majority of transplant recipients did not develop an appreciable humoral response following SARS-CoV-2 vaccine, in contrast to dialysis patients and healthy individuals. We analyzed the serologic response to BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of 19 kidney transplant recipients, vaccinated prior to transplantation, compare to 109 recipients vaccinated after transplantation, and to 39 healthcare workers, by determining the level of anti-spike antibodies after transplantation. All controls and 17 of 19 (90%) of recipients vaccinated before transplant were seropositive, while only 49 of 109 (45%) recipients vaccinated post-transplant had positive serology (P < .001). Median anti-spike IgG in the group of kidney transplant recipients vaccinated after transplantation (10.7 AU/ml, [IQR 0-62.5]) was lower than the patients vaccinated before transplantation (66.2 AU/ml [21.6-138]), which was significantly lower than in the controls (156 AU/ml [99.7-215.5]). Negative humoral response was associated with vaccination post transplantation (odds ratio 22.4), older age (OR = 1.04), and longer time on dialysis (OR = 1.02), while higher lymphocyte count at time of vaccination was protective (OR = .52). Our findings of sustained superior humoral response to SARS-CoV-2 vaccine in kidney transplant recipients vaccinated prior to transplantation strongly support the recommendations of SARS-CoV-2 vaccination of transplant candidates, especially those younger than 60 years.