Consistent efficacy outcomes between phase 2 and phase 3 trials in Crohn's disease or ulcerative colitis in adults: a meta-analysis.

INTRODUCTION: The approval of novel biologic agents and small molecules for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) is dependent on phase 3 randomized controlled trials (RCTs). However, these trials sometimes fail to achieve the expected efficacy outcomes observed in phase 2 trials. METHODS: We conducted a systematic review of RCTs that evaluated biologic agents and small molecules using paired regimens in both phase 2 and phase 3. We searched Medline, EMBASE, and Cochrane databases up until February 13, 2024. The revised Cochrane tool was utilized to assess the risk of bias. A generalized linear mixed-effects model (GLMM) was employed to estimate the odds ratios (ORs) for efficacy outcomes in phase 2 trials compared to phase 3. RESULTS: We identified a total of 23 trials with 10 paired regimens for CD and 30 trials with 11 paired regimens for UC. The GLMM analysis revealed that phase 2 CD trials had higher outcomes measured by the Crohn's Disease Activity Index (CDAI) by 9-13% without statistical significance: CDAI-150: OR, 1.12 (95% CI 0.83-1.51, p = 0.41); CDAI-100: OR, 1.09 (95% CI 0.88-1.35, p = 0.40); or CDAI-70: OR, 1.13 (95% CI 0.61-2.08, p = 0.66). For UC, two efficacy outcomes were estimated to be equally reported in phase 2/phase 3 pairs: clinical remission: OR, 1.00 (95% CI 0.83-1.20, p = 0.96); endoscopic improvement: OR, 0.98 (95% CI 0.83-1.15, p = 0.79). However, the rate of clinical response was underestimated in phase 2 by 19%: OR, 0.81 (95% CI 0.70-0.95, p = 0.03). The inclusion criterion for the type of Mayo score for UC had a significant interaction with the study phase to influence the difference in clinical response (p = 0.002). CONCLUSIONS: Our findings suggest that the main efficacy outcomes for CD and UC remain consistent between phase 2 and phase 3 trials, except for UC response rates. The efficacy data obtained from phase 2 trials can be considered reliable for the design of subsequent phase 3 trials. REGISTRATION: PROSPERO (CRD42023407947).

Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses.

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

Fragility index analysis for randomized controlled trials of approved biologicals and small molecule drugs in inflammatory bowel diseases.

INTRODUCTION: Biologics and small molecules have been increasingly applied in Crohn's disease (CD) and ulcerative colitis (UC). But the robustness of their trials has not been evaluated. METHODS: We initially collected all the approved biologics or small molecules for CD or UC up to December 1, 2022. Databases were then queried by keywords in chemical name and CD or UC. Randomized controlled trials (RCTs) in the two-arm, 1:1 design were included. Fragility index (FI) and fragility quotient (FQ) were subsequently calculated. RESULTS: We included twenty-eight RCTs, including nine pivotal trials listed in approval labels, nineteen non-pivotal trials not included in the labels. The median sample size was 99 [IQR, 60-262] and the median number of loss-of-follow-up (LFU) was 14 [IQR, 8-43]. Pivotal trials in the labels had the median FI of 8 [IQR, 4-14, n = 6] that was marginally higher than non-pivotal trials (3 [IQR, 2-4], p = 0.08). The median FQ was 0.0330 [IQR, 0.1220-0.0466] and 0.0310 [IQR, 0.0129-0.0540] for pivotal and non-pivotal trials, respectively (p = 1.0). The sample size and FI were significantly correlated (Spearman correlation coefficient [r] = 0.56, 95 %CI 0.21-0.78, p = 0.003). The number of total events was also significantly correlated with FI (r = 0.53, 95 %CI 0.17-0.77, p = 0.006). Study p-values were significantly associated with FI (p = 0.01): trials with p-values < 0.001 had the highest median FI of 10 [IQR, 6-17]. No factor was found strongly correlated with FQ. CONCLUSION: Results from trials assessing administration-approved biologics or small molecules for treating CD or UC were vulnerable to small changes by measuring FI or FQ. Pivotal studies contributing to regulatory approvals exhibited a relatively higher degree of resilience compared to non-pivotal trials.

Comparative effectiveness and safety of ustekinumab at different intervals of maintenance phase in inflammatory bowel disease: a systematic review and meta-analysis.

Ustekinumab has two alternative drug maintenance intervals for inflammatory bowel disease (IBD), every 8 weeks (Q8W) and every 12 weeks (Q12W). The current study aimed at evaluating the comparative efficacy and safety of the two maintenance intervals in patients with IBD. A systematic search on PubMed, Web of Science, Cochrane Library, and EMBASE was carried out. The relative risk (RR) was pooled for efficacy and safety outcomes between the two intervals at various follow-up time points, categorized as short term (less than 44 weeks), medium term (about 92 weeks), and long term (about 152 weeks). A total of 14 studies with 1448 patients were included. Q8W didn't result in a remarkably higher proportion of clinical remission compared to Q12W at short term (RR, 0.99; 95% CI, 0.83-1.16), medium term (RR, 1.05; 95% CI, 0.91-1.20), and long term (RR, 1.07; 95% CI, 0.91-1.26). Similarly, no substantial differences exist at short term in clinical response (RR, 1.00; 95% CI, 0.85-1.17), endoscopic remission (RR, 0.97; 95% CI, 0.26-3.69), and histologic improvement (RR, 1.13; 95% CI, 0.93-1.36) between the two intervals. For safety outcomes, the RR values for any adverse events in the short, medium, and long term were 1.10 (95% CI, 1.00-1.21), 1.14 (95% CI, 1.08-1.20), and 1.12 (95% CI, 1.07-1.17) for Q8W versus Q12W. Finally, we conclude that ustekinumab maintenance therapy administered every 8 and 12 weeks showed similar effectiveness in achieving efficacy outcomes in IBD patients, and most safety outcomes were significantly better for Q12W during the maintenance phase.

The influence of sleep factors and dietary habits on the disease pattern of ulcerative colitis patients with long and short disease courses - a multicentre cross-sectional analysis.

BACKGROUND: Ulcerative colitis (UC) is a disease characterized by chronic relapsing-remitting inflammatory disorders and is associated with environmental changes. AIM: To explore the disease patterns of Chinese UC patients and to determine controllable related environmental factors. METHODS: This multicentre cross-sectional study was performed using a questionnaire survey. Data on clinical characteristics and environmental factors were collected. Patients with a disease course ≥5 years were defined as the long course group, and those with a disease course < 5 years were defined as the short course group. RESULTS: A total of 588 effective questionnaires were collected. The proportion of the chronic continuous pattern was the highest among patients with a long disease course (46.8%), and in patients with a short disease course, the proportion of the active to remission pattern was the highest (53.3%). In patients with a long disease course, a higher proportion of patients with adequate sleep was found in the active to remission pattern than in the chronic intermittent (72.1% vs. 43.3%, p = 0.008) and chronic continuous (72.1% vs. 52.4%, p = 0.016) patterns. In patients with a short disease course, the frequency of shellfish and shrimp was higher in the chronic continuous pattern group than in the active to remission pattern group (P = 0.001 and 0.017 respectively). CONCLUSIONS: For early diagnosis patients, dietary guidance should be actively carried out. With the prolongation of the disease course, attention should be given to the sleep quality of patients.

1.UC exhibits various disease patterns, which may be associated with differences in patient prognosis and treatment response.2.Environmental factors, especially sleep and dietary factors, correlated strongly with disease patterns, which varied in different disease courses.3.Early diagnosis patients should receive active dietary guidance, while patients with a prolonged disease course require attention to their sleep quality and appropriate drug interventions when necessary.

A Shortened Diagnostic Interval and Its Associated Clinical Factors and Related Outcomes in Inflammatory Bowel Disease Patients from a Cohort Study in China.

Aim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined. Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval. Results: A total of 516 and 848 patients were confirmed to have Crohn's disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P<0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51-60 years and 12.5 months in UC patients at the age of 41-50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay. Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.

Burnout among radiology residents: a systematic review and meta-analysis.

OBJECTIVE: To analyze the prevalence of burnout among radiology residents. METHOD: Five databases (PubMed, Web of Science, Embase, PsycINFO, and Scopus) were searched for studies reporting burnout in radiology residents for the period up to November 7, 2022. RESULTS: A total of 423 studies were identified, and eventually, 16 studies were selected for the qualitative analysis, of which 11 studies were used in the meta-analysis. There was a total of 2164 radiology residents. Six studies reported the prevalence of burnout but the data could not be pooled due to their inconsistent definitions of burnout. The mean scores of three burnout subscales indicated a moderate to high degree of severity: emotional exhaustion = 25.2 (95% CI, 22.1-28.3; I2 = 94.4%), depersonalization = 10.2 (95% CI, 8.5-11.9; I2 = 93.0%), and low perception of personal accomplishment = 32.9 (95% CI, 30.5-35.4; I2 = 94.4%). The pooled prevalence of high-degree emotional exhaustion was 49.9% (95% CI, 43.6-56.1%; I2 = 55.7%), high-degree depersonalization was 45.1% (95% CI, 38.3-52.0%; I2 = 63.2%), and high-degree diminished personal accomplishment was 58.2% (95% CI, 36.0-77.6%; I2 = 84.9%). The impact of the COVID-19 pandemic on radiology residents was not investigated. In addition, there are inconsistent findings on the effects of female sex, seniority, and social support on burnout. CONCLUSIONS: About half of the radiology residents showed at least one of the three burnout manifestations (emotional exhaustion, depersonalization, and personal accomplishment), with a moderate to high degree of severity. CLINICAL RELEVANCE STATEMENT: Such a high prevalence and severity of burnout among radiology residents warrant the attention of residency program directors. KEY POINTS: • Burnout, not uncommon among radiology residents, has not been effectively analyzed. • Nearly half of the radiology residents experience at least one of the three manifestations of burnout to a moderate to high degree. • The high prevalence and severe degree of burnout among radiology residents warrant the attention of residency program directors.

Differences in the incidence and mortality of digestive cancer between Global Cancer Observatory 2020 and Global Burden of Disease 2019.

The burden of digestive cancers is increasing worldwide. The Global Cancer Observatory (GLOBOCAN) 2020 and the Global Burden of Disease (GBD) 2019 are two primary cancer databases, which have a significant impact on policy formulation and resource allocation. We aim to compare the incidence and mortality of digestive cancers between them. Digestive cancer (esophageal, stomach, colorectal, liver, gallbladder and pancreatic cancer) incidence was obtained from the Cancer Today and GBD 2019 result tool. The top five countries with the most or minor difference between GLOBOCAN 2020 and GBD 2019 in age-standardized incidence rates (ASIRs) of digestive cancers were identified. A systematic search on the incidence of specific digestive cancer in selected countries from PubMed and Embase was conducted, and 20 of 281 publications were included. The most significant differences in digestive cancers incidence were commonly found in Asian countries (70%), particularly Indonesia, Vietnam and Myanmar, located in Southeast Asia. The ASIRs for most digestive cancers, except liver cancer, in GLOBOCAN 2020 were higher than those in GBD 2019. Gallbladder cancer had the highest average ratio, followed by liver cancer. The most commonly used standard population was Segi's standard population, followed by the World Health Organization standard population. The data sources nor the processing methods of GLOBOCAN 2020 and GBD 2019 were not similar. Low- and middle-income countries without population-based cancer registries were more likely to have selection bias in data collection and amplify regional variations of etiological factors. Better judgments on the quality of cancer data can be made.

A Study on the Applicability of Aromatic Parameters in the Maturity Evaluation of Lacustrine Source Rocks and Oils Based on Pyrolysis Simulation Experiments.

Aromatic maturity parameters were evaluated via closed-system pyrolysis experiments using a Mesozoic lacustrine source rock from the Yingen-Ejinaqi Basin, thereby ensuring a uniform source. Pulverized rock aliquots (200 mg) were reacted with water at temperatures ranging from 250 to 550 °C at 5 °C/min, and the aromatic fractions of expelled oil and extracts of the solid residue were analyzed by GC-MS. The experiments showed that the relative abundance of aromatic hydrocarbons in the oil and extractable organic matter (EOM) of source rock had different evolutionary characteristics. With the increase in the thermal evolution degree, the relative abundance of aromatic hydrocarbons in the EOM showed the characteristics of ″increased early (Ro < 0.80), unchanged middle (Ro = 0.80-2.00%), decreased lately (Ro > 2.00%)″. While the relative abundance of aromatic hydrocarbons in the expelled oils continuously increased, as the Ro values increased from 0.62 to 2.39%, the relative abundance of aromatic hydrocarbons gradually increased from 8 to 46%. With increased maturity, the relative abundance of 1-3-ring aromatic hydrocarbons continuously decreased, as observed in the phenanthrene homologs. Meanwhile, the relative abundance of 4+-ring aromatic hydrocarbons continuously increased, as seen in chrysene homologs. It was suggested that the effects of maturity on the composition of aromatic hydrocarbons might not be sufficiently obvious. The effective application range of the alkylnaphthalene-related maturity parameters (2-/1-methylnaphthalenes, (2,6- + 2,7-)/1,5-dimethylnaphthalenes, 2,3,6-/(1,4,6- + 1,3,5-) trimethylnaphthalenes, and (2,3,6- + 1,3,7-)/(1,4,6- + 1,3,5- + 1,3,6-) trimethylnaphthalenes) and the alkyldibenzothiophene maturity parameters (4-/1-methyldibenzothiophenes, 4,6-/(1,4- + 1,6-) dimethyldibenzothiophenes, and (2,6- + 3,6-)/(1,4- + 1,6-) dimethyldibenzothiophenes) was 0.84-2.06% Ro. The alkylphenanthrene-related maturity parameters had a wide application range for lacustrine source rocks with an Ro < 2.06%. These parameters included 1.5 × (2- + 3-)/(phenanthrene +1- + 9-) methylphenanthrenes, 3 × 2-/(phenanthrene + 1- + 9-) methylphenanthrenes, (2- + 3-)/(1- + 9-) methylphenanthrenes, 2-/1-methylphenanthrenes, (3- + 2-)/(1- + 2- + 3- + 9-) methylphenanthrenes, 2-/(1- + 2- + 3- + 9-) methylphenanthrenes, and 2,7-/1,8-dimethylphenanthrenes. In addition, the effective applicable range of the methylnaphthalene-related maturity parameter 3-/1-methylchrysenes was an Ro value less than 1.79%. The results clarified the validity scope of some aromatics' maturity parameters and provided a theoretical basis for the scientific application of these parameters.

Malnutrition Defined by the Global Leadership Initiative on Malnutrition (GLIM) Criteria in Hospitalized Patients with Ulcerative Colitis and Its Association with Clinical Outcomes.

(1) Background: The Global Leadership Initiative on Malnutrition (GLIM) was published in 2019, and its application has been explored in several diseases. However, the data on malnutrition based on the GLIM in ulcerative colitis (UC) patients are sparse. (2) Methods: This single-center, retrospective cohort study included 605 hospitalized UC patients. Demographics and clinical data were collected from electronic medical records. Nutritional Risk Screening 2002 (NRS 2002) was used as a screening tool, and malnutrition was diagnosed according to the GLIM criteria. The skeletal muscle area of the third lumber cross-section in abdominal computed tomography was used to evaluate muscle mass within one week before or after admission. (3) Results: The prevalence of malnutrition was 64.1% in this cohort, and the prevalences were 34.2, 57.7, and 86.7% in UC patients with mild, moderate, and severe disease activity, respectively. Malnourished patients tended to need surgical treatment (p = 0.080) and had a 2.4 times greater risk of opportunistic infection. The multivariate logistic regression analysis showed that UC patients with malnutrition had a 1.7-fold increased risk of readmission. (4) Conclusions: Nutritional problems deserve more attention in hospitalized UC patients. Malnutrition identified through the GLIM criteria was associated with opportunistic infection, tended to be associated with surgical treatment, and showed a prognosis value for readmission.

The prevalence of burnout among pulmonologists or respiratory therapists pre- and post-COVID-19: a systematic review and meta-analysis.

OBJECTIVES: The coronavirus disease-19 (COVID-19) increased the already heavy workload in the pulmonary and respiratory departments, which therefore possibly increased the prevalence of burnout among pulmonologists or respiratory therapists. We aimed to compare the differences in burnout among pulmonologists or respiratory therapists pre- and post-COVID-19 by doing a systematic review with meta-analysis. METHODS: We searched pulmonologist, or pulmonary, or respiratory, and burnout up to 29 January 2023 in six databases. We included studies investigating pulmonologists or respiratory therapists and reporting the prevalence of burnout among them. The risk of bias was assessed by a tool for prevalence studies. The overall prevalence of burnout was pooled. RESULTS: A total of 2859 records were identified and 16 studies were included in the final analysis. The included studies reported 3610 responding individuals and 2336 burnouts. The pooled prevalence of burnout was 61.7% (95% confidence interval (CI), 48.6-73.2%; I2 = 96.3%). The pooled prevalence of burnout during COVID-19 was significantly higher than it was prior to the outbreak (68.4% vs. 41.6%, p = .01). The result of the meta-regression revealed that COVID-19 coverage was significantly associated with the prevalence of burnout (p = .04). CONCLUSIONS: Burnout was widely prevalent among pulmonologists or respiratory therapists and increasingly perceived during COVID-19. Therefore, interventions were needed to reduce burnout in this specialty.KEY MESSASGESThe coronavirus disease-19 increased the already heavy workload in the pulmonary and respiratory departments.Burnout was widely prevalent among pulmonologists or respiratory therapists and increasingly perceived during COVID-19.

Distinct lipid profile in haemolytic anaemia-related gallstones compared with the general gallstone.

BACKGROUND: Pigment gallstones are not uncommon among patients with chronic haemolytic anaemia. But their clinical characteristics have not been described in detail and not been directly compared with the general gallstone population. METHODS: Patients at Peking Union Medical College Hospital with haemolytic anaemia and subsequent gallstones from January 2012 to December 2022 were included. Cases were matched (1:2) based on age, sex and location of stones to randomly select non-anaemia patients with gallstones (controls). RESULTS: Screening 899 cases of gallstones, we finally included 76 cases and 152 controls. Total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) for cases were 3.02 ± 0.98 mmol/L, 0.89 ± 0.30 mmol/L and 1.58 ± 0.70 mmol/L, respectively, significantly lower than those in the control group (all p < 0.001). TC and HDL were both lower than the normal range, but triglyceride and LDL were within the normal range. Multiple stones were significantly more common for cases (n = 59, 78%) than for controls (n = 44, 29%, p < 0.001). The mean diameter of the maximal gallstone was 1.2 ± 0.6 cm and 1.5 ± 1.0 cm for cases and controls (p = 0.120), respectively. Stones in the elderly (p = 0.002 for univariate analysis, and 0.001 for multivariate analysis) and stones in the bile duct (p = 0.005 for univariate analysis, and 0.009 for multivariate analysis) were found to occur in a shorter period after anaemia. CONCLUSION: The lipid profile of haemolytic anaemia with gallstones was distinct, low TC, low HDL, and increased-to-normal LDL, compared with the general gallstone population. Patients with haemolytic anaemia were recommended an abdominal ultrasound if aged older than 50 years, with more frequent follow-up visits.KEY MESSAGESClinical characteristics of gallstones following chronic haemolytic anaemia were described and compared with the general gallstone population.The lipid profiles were distinctly different between the patients with gallstones following chronic haemolytic anaemia and the general gallstone population.Elder patients were complicated with gallstones in a shorter period after anaemia and thus were recommended an abdominal ultrasound if aged older than 50 years, with more frequent follow-up visits.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy.

BACKGROUND: A high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. METHODS: Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as 'improvement' and 'non-improvement' (including 'no change' and 'exacerbation'). RESULTS: Among 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. CONCLUSIONS: Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Neostigmine for non-mild acute pancreatitis: A systematic review and meta-analysis of randomized controlled trials.

Background: The therapeutic value of neostigmine as a prokinetic drug in acute pancreatitis (AP), especially in non-mild AP, including moderately severe and severe AP remains controversial. This meta-analysis aimed to investigate the efficacy of neostigmine treatment in patients with non-mild AP. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases up to 24 December 2022 for RCTs comparing neostigmine plus conventional treatment versus the conventional treatment alone in patients with non-mild AP. Trial sequential analyses (TSA) were used to assess the risk of random errors and the results. Results: Six RCTs with 318 participants were included. Compared with conventional treatment, patients who received neostigmine plus conventional treatment had a shorter time duration for their first defecation (MD: -1.74; 95% CI: -2.10 to -1.38; p < 0.00001; n = 205; RCTs = 4; low quality of evidence) and better relief time of abdominal symptoms (MD: -1.59, 95% CI: -2.07 to -1.11; p < 0.00001; n = 155; RCTs = 3; low quality of evidence) as primary outcomes, and a faster percentage decrease of IAP at 24 h (p = 0.0005; moderate quality of evidence) and a shorter length of ICU stay (p < 0.00001; moderate quality of evidence) as partial secondary outcomes. TSA suggested the sample size was limited, but the cumulative Z curves of the primary outcomes crossed the conventional boundary and the trial sequential monitoring boundary. Conclusion: For patients with non-mild AP, neostigmine promotes the recovery of gastrointestinal motility and may have positive effects on the improvement of a clinical prognosis. Further large-sample studies are needed for a definite conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/; Identifier: CRD 42022381417.

Elderly Patients with Moderate-To-Severe Ulcerative Colitis Are More Likely to Have Treatment Failure and Adverse Outcome.

BACKGROUND AND AIM: The aim of this study was to compare therapeutic responses and prognosis between elderly and nonelderly ulcerative colitis (UC) patients with moderate-to-severe activity. METHODS: 148 UC patients with moderate-to-severe activity hospitalized between 2000 and 2019 were enrolled consecutively, including 74 patients with the age of diagnosis over 60 years and 74 patients diagnosed less than 60 years. Patients were matched by gender, duration (±15%), disease activity, and admission time (±1 year). They were followed up until the latest medical record or December 2019. The primary outcome was UC-related colectomy or death. RESULTS: 148 patients were followed over median 37.5 months. For steroid use, 76.8% of elderly UC patients were responsive, lower than that in adult group (85.7%). A decreased level of clinical activity index (2.0 [-1.5 to 4.00] vs. 6.0 [3.0-8.0], p < 0.001), reduction of C-reactive protein (23.9 [3.5-65.5] vs. 27.8 [9.7-58.1] mg/L), and erythrocyte sedimentation rate (9.0 [-1.3 to 30.5] vs. 15.5 [3.8-36.5] mm/h) at 4 weeks after steroid induction was less obvious in the elderly. More elderly patients manifested steroid dependence and resistance. 28.4% of elderly UC patients took colectomy, remarkably more than adult patients (12.2%), which also occurred earlier (8.0 [0.5-44.75] vs. 39.5 [12-57.38] months, p = 0.001). Aging (hazard ratio [HR] 2.868, 95% confidence interval [CI]: 1.290-6.375, p = 0.01), male, steroid resistance, and occurrence of complications were independently related to colectomy. The rate of serious infections was significantly higher in the elderly (55.4% vs. 35.1%, p = 0.013), mainly including cytomegalovirus infection, bacterial infection, and extraintestinal infection. Aging (odds ratio [OR] 2.774, 95% CI: 1.355-5.675, p = 0.015), extensive colonic involvement, steroid resistance, and biologics usage were independently associated with a high risk of concomitant infections. CONCLUSION: Elderly patients with moderate-to-severe UC experienced more treatment failure and increased risk of UC-related colectomy, mortality, and severe infections, predicting demand for more strict and individualized management.

ST2 and CSF-1 as potential druggable targets of inflammatory bowel diseases: Results from two-sample Mendelian randomization study.

Novel druggable targets are warranted for inflammatory bowel disease (IBD) treatment. We aimed to identify novel circulating proteins with causal associations with the risk of IBDs and provide potential therapeutic targets for IBD treatment. We performed a two-sample Mendelian randomization (MR) study to explore the associations of 55 circulating biomarkers on the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC) by leveraging the summary statistics from large genomewide association studies and protein quantitative trait loci studies. The individual estimate was pooled together by meta-analyses to estimate the causal effects of each outcome. In univariable MR, we identified several circulating proteins showed potential correlation with IBD, UC, and CD. Of note, we observed that a genetically proxied increased level of suppression of tumorigenicity 2 (ST2) was associated with an elevated risk of IBD (odds ratios [ORs] 1.133, 95% confidence interval [CI] 1.091-1.176, p < 0.0001), CD (ORs 1.188, 95% CI 1.103-1.281, p < 0.0001), and UC cohorts (ORs 1.087, 95% CI 1.050-1.125, p < 0.0001). Additionally, we observed a consistent positive correlation between the level of CSF-1 and the increased risk of IBD in individual MR, with statistically significant causal associations in the meta-analyses with ORs equal to 1.217 (IBD, 95% CI 1.115-1.328, p < 0.0001), 1.223 (CD, 95% CI 1.082-1.382, p = 0.0013), and 1.179 (UC, 95% CI 1.055-1.317, p = 0.0037). This study provided evidence for potential casual associations between circulating ST2 and CSF-1 levels, and increased risks of IBD, UC, and CD, implicating potential treatment targets for IBD and subtypes.