Nalmefene, an opioid receptor modulator, aggravates atherosclerotic plaque formation in apolipoprotein E knockout mice by enhancing oxidized low-density lipoprotein uptake in macrophages.

Nalmefene, an antagonist of mu- and delta-opioid receptors and a partial agonist of kappa-opioid receptors, has shown promise in reducing alcohol consumption among patients with alcohol dependence. Opioid receptors play pivotal roles in various physiological processes, including those related to peripheral inflammatory diseases such as colitis and arthritis, as well as functions in the immune system and phagocytosis. Atherosclerosis, a chronic inflammatory disease, progresses through the phagocytosis and uptake of oxidized low-density lipoprotein (oxLDL) by macrophages in atherosclerotic plaques. Despite this knowledge, it remains unclear whether nalmefene influences the formation of atherosclerotic plaques and increases the risk of serious cardiovascular events. This study aims to elucidate the impact of nalmefene on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and peritoneal macrophages in vitro. In this experiment, 8-week-old male ApoE KO mice were fed a high-fat diet intraperitoneally administered either vehicle (saline) or nalmefene (1 mg and 3 mg kg-1 day-1) for 21 days. Oil red O-staining and immunohistochemistry with an anti-MOMA2 (monocyte/macrophage) antibody showed that a dose-dependent increase in atherosclerotic plaque formation and augmentation of macrophage-rich plaque formation in ApoE-KO mice. Further investigations focused on the effects of nalmefene on the expression of scavenger receptor CD36 in RAW264.7 cells, conducted through western blotting analysis. Nalmefene demonstrated a significant increase in CD36 protein expression in RAW264.7 cells. To explore the impact on oxidized LDL uptake in peritoneal macrophages, cells were treated with nalmefene (300 µg/mL) for 24 h, followed by the addition of DiI-labeled oxLDL (DiI-oxLDL) for 4 h. Nalmefene significantly enhanced DiI-oxLDL uptake in macrophages. Additionally, treatment with nalmefene (300 µg/mL) for 24 h decreased the mRNA expression of mu-, delta-, and kappa-opioid receptors in RAW264.7 cells. In conclusion, nalmefene may augment oxLDL uptake by macrophages through increased CD36 expression and decreased opioid receptor, thereby contributing to atherosclerotic plaque formation and vulnerability. Consequently, the use of nalmefene may be associated with an elevated risk of cardiovascular events.

A novel prediction tool for mortality in patients with acute lower gastrointestinal bleeding requiring emergency hospitalization: a large multicenter study.

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.

High risk stigmata and treatment strategy for acute lower gastrointestinal bleeding: a nationwide study in Japan.

BACKGROUND: The rebleeding risks and outcomes of endoscopic treatment for acute lower gastrointestinal bleeding (ALGIB) may differ depending on the bleeding location, type, and etiology of stigmata of recent hemorrhage (SRH) but have yet to be fully investigated. We aimed to identify high risk endoscopic SRH and to propose an optimal endoscopic treatment strategy. METHODS: We retrospectively analyzed 2699 ALGIB patients with SRH at 49 hospitals (CODE BLUE-J Study), of whom 88.6 % received endoscopic treatment. RESULTS: 30-day rebleeding rates of untreated SRH significantly differed among locations (left colon 15.5 % vs. right colon 28.6 %) and etiologies (diverticular bleeding 27.5 % vs. others [e. g. ulcerative lesions or angioectasia] 8.9 %), but not among bleeding types. Endoscopic treatment reduced the overall rebleeding rate (adjusted odds ratio [AOR] 0.69; 95 %CI 0.49-0.98), and the treatment effect was significant in right-colon SRH (AOR 0.46; 95 %CI 0.29-0.72) but not in left-colon SRH. The effect was observed in both active and nonactive types, but was not statistically significant. Moreover, the effect was significant for diverticular bleeding (AOR 0.60; 95 %CI 0.41-0.88) but not for other diseases. When focusing on treatment type, the effectiveness was not significantly different between clipping and other modalities for most SRH, whereas ligation was significantly more effective than clipping in right-colon diverticular bleeding. CONCLUSIONS: A population-level endoscopy dataset allowed us to identify high risk endoscopic SRH and propose a simple endoscopic treatment strategy for ALGIB. Unlike upper gastrointestinal bleeding, the rebleeding risks for ALGIB depend on colonic location, bleeding etiology, and treatment modality.

Evolution of sensitivity to warning cues from kin in plants with a structured population.

Plants exchange a variety of information intra- and interspecifically by using various mediating cues. For example, plant individuals that are injured by herbivores release volatile chemicals, which induce receiver plants to express anti-herbivore resistance. Remarkably, some plant species were known to represent kin specificity in the response, where cues from a damaged individual induce a higher level of resistance in a kin receiver than in a non-kin receiver. Such higher sensitivity to warning cues from kin could be advantageous via two mechanisms. If each herbivore tends to attack plants with a certain genotype, plants should be more sensitive to warning cues from kin that share genetic properties. In addition, if herbivores successively attack the neighboring plant with a high probability, and if related plants tend to grow in close proximity, plants may be more sensitive to warning cues from neighboring kin under the presence of a trade-off between sensitivity to kin and non-kin. In the present study, we constructed a mathematical model including those mechanisms to investigate the evolutionary process of the higher sensitivity to warning cues from kin than sensitivities to cues from non-kin. According to the analysis of evolutionary dynamics, we revealed that both mechanisms could contribute, although higher sensitivity to cues from kin is more likely to evolve when the spatial range of competition is greater than the range of effective alarm cues. This result highlights the importance of the competition regime in the evolution of signaling among kin.

Effect of Dapagliflozin on Serum Uric Acid Levels in Patients with Advanced Chronic Kidney Disease.

Objective Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are hypoglycemic agents, have been shown to be cardioprotective through a variety of mechanisms, and the effect of lowering uric acid (UA) levels may be one of the mechanisms. In the present retrospective study, we investigated the changes in serum UA levels in patients with chronic kidney disease (CKD) treated with SGLT2 inhibitors. Methods We included 31 patients with CKD who were newly started on dapagliflozin for renal protection and evaluated trends in various parameters, including serum UA levels and UA excretion from urine. Results The patients' median age was 71 years old, 20 patients were men, 7 patients had diabetes, and the median estimated glomerular filtration rate was 33.9 mL/min/1.73 m2 (CKD stage 3: 21 cases, stage 4: 10 cases). The differences in UA and fractional excretion of UA after three weeks and three months of prescription showed significantly decreased UA values and an increased fractional excretion of UA. Conclusion Our findings suggest that dapagliflozin can lower serum UA levels via increased UA excretion, even in patients with advanced CKD.

Characteristics, outcomes, and risk factors of surgery for acute lower gastrointestinal bleeding: nationwide cohort study of 10,342 hematochezia cases.

BACKGROUND: Current evidence on the surgical rate, indication, procedure, risk factors, mortality, and postoperative rebleeding for acute lower gastrointestinal bleeding (ALGIB) is limited. METHODS: We constructed a retrospective cohort of 10,342 patients admitted for acute hematochezia at 49 hospitals (CODE BLUE J-Study) and evaluated clinical data on the surgeries performed. RESULTS: Surgery was performed in 1.3% (136/10342) of the cohort with high rates of colonoscopy (87.7%) and endoscopic hemostasis (26.7%). Indications for surgery included colonic diverticular bleeding (24%), colorectal cancer (22%), and small bowel bleeding (16%). Sixty-four percent of surgeries were for hemostasis for severe refractory bleeding. Postoperative rebleeding rates were 22% in patients with presumptive or obscure preoperative identification of the bleeding source and 12% in those with definitive identification. Thirty-day mortality rates were 1.5% and 0.8% in patients with and without surgery, respectively. Multivariate analysis showed that surgery-related risk factors were transfusion need ≥ 6 units (P < 0.001), in-hospital rebleeding (P < 0.001), small bowel bleeding (P < 0.001), colorectal cancer (P < 0.001), and hemorrhoids (P < 0.001). Endoscopic hemostasis was negatively associated with surgery (P = 0.003). For small bowel bleeding, the surgery rate was significantly lower in patients with endoscopic hemostasis as 2% compared to 12% without endoscopic hemostasis. CONCLUSIONS: Our cohort study elucidated the outcomes and risks of the surgery. Extensive exploration including the small bowel to identify the source of bleeding and endoscopic hemostasis may reduce unnecessary surgery and improve the management of ALGIB.

Association of direct oral anticoagulant and delayed bleeding with pharmacokinetics after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Pharmacokinetic parameters, such as drug plasma level at trough and time to maximum plasma concentration (Tmax), and coagulation factor Xa (FXa) activity, generally predict factors for the anti-coagulant effects of direct oral anticoagulants (DOACs). Although gastrointestinal bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacological parameters. This study aimed to evaluate pharmacological risk factors for post-ESD bleeding in patients taking DOAC. METHODS: We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions, and investigated the association with post-ESD bleeding and pharmacological factors, including plasma concentration and FXa activity at trough and Tmax. RESULTS: The incidence of post-ESD bleeding was 12.8% (95% confidence interval [CI]: 7.2%-20.6%, 14/109). Although plasma DOAC concentration and plasma level/dose ratio at trough and Tmax varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893, p <0.001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR]: 1.192, 95% CI: 1.020-1.392, p=0.027) and high anti-coagulant ability analyzed by FXa activity at trough and Tmax (OR: 6.056, 95% CI: 1.094-33.529, p=0.039). CONCLUSIONS: The incidence of post-ESD bleeding taking DOAC was high, especially in aged patients and with high anti-coagulant effects. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding.

Early feeding reduces length of hospital stay in patients with acute lower gastrointestinal bleeding: A large multicentre cohort study.

AIM: No studies have compared the clinical outcomes of early and delayed feeding in patients with acute lower gastrointestinal bleeding (ALGIB). This study aimed to evaluate the benefits and risks of early feeding in a nationwide cohort of patients with ALGIB in whom haemostasis was achieved. METHODS: We reviewed data for 5910 patients with ALGIB in whom haemostasis was achieved and feeding was resumed within 3 days after colonoscopy at 49 hospitals across Japan (CODE BLUE-J Study). Patients were divided into an early feeding group (≤1 day, n = 3324) and a delayed feeding group (2-3 days, n = 2586). Clinical outcomes were compared between the groups by propensity matching analysis of 1508 pairs. RESULTS: There was no significant difference between the early and delayed feeding groups in the rebleeding rate within 7 days after colonoscopy (9.4% vs. 8.0%; p = 0.196) or in the rebleeding rate within 30 days (11.4% vs. 11.5%; p = 0.909). There was also no significant between-group difference in the need for interventional radiology or surgery or in mortality. However, the median length of hospital stay after colonoscopy was significantly shorter in the early feeding group (5 vs. 7 days; p < 0.001). These results were unchanged when subgroups of presumptive and definitive colonic diverticular bleeding were compared. CONCLUSION: The findings of this nationwide study suggest that early feeding after haemostasis can shorten the hospital stay in patients with ALGIB without increasing the risk of rebleeding.

Weekend Effect on Clinical Outcomes of Acute Lower Gastrointestinal Bleeding: A Large Multicenter Cohort Study in Japan.

INTRODUCTION: Weekend admissions showed increased mortality in several medical conditions. This study aimed to examine the weekend effect on acute lower gastrointestinal bleeding (ALGIB) and its mortality and other outcomes. METHODS: This retrospective cohort study (CODE BLUE-J Study) was conducted at 49 Japanese hospitals between January 2010 and December 2019. In total, 8,120 outpatients with acute hematochezia were enrolled and divided into weekend admissions and weekday admissions groups. Multiple imputation (MI) was used to handle missing values, followed by propensity score matching (PSM) to compare outcomes. The primary outcome was mortality; the secondary outcomes were rebleeding, length of stay (LOS), blood transfusion, thromboembolism, endoscopic treatment, the need for interventional radiology, and the need for surgery. Colonoscopy and computed tomography (CT) management were also evaluated. RESULTS: Before PSM, there was no significant difference in mortality (1.3% vs. 0.9%, p = 0.133) between weekend and weekday admissions. After PSM with MI, 1,976 cases were matched for each admission. Mortality was not significantly different for weekend admissions compared with weekday admissions (odds ratio [OR] 1.437, 95% confidence interval [CI] 0.785-2.630; p = 0.340). No significant difference was found with other secondary outcomes in weekend admissions except for blood transfusion (OR 1.239, 95% CI 1.084-1.417; p = 0.006). Weekend admission had a negative effect on early colonoscopy (OR 0.536, 95% CI 0.471-0.609; p < 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295-1.660; p < 0.001). CONCLUSION: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding - A Multicenter Nationwide Study.

INTRODUCTION: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). METHODS: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. RESULTS: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. CONCLUSIONS: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Bortezomib Increased Vascular Permeability by Decreasing Cell-Cell Junction Molecules in Human Pulmonary Microvascular Endothelial Cells.

Bortezomib (BTZ), a chemotherapeutic drug used to treat multiple myeloma, induces life-threatening side effects, including severe pulmonary toxicity. However, the mechanisms underlying these effects remain unclear. The objectives of this study were to (1) investigate whether BTZ influences vascular permeability and (2) clarify the effect of BTZ on the expression of molecules associated with cell-cell junctions using human pulmonary microvascular endothelial cells in vitro. Clinically relevant concentrations of BTZ induced limited cytotoxicity and increased the permeability of human pulmonary microvascular endothelial cell monolayers. BTZ decreased the protein expression of claudin-5, occludin, and VE-cadherin but not that of ZO-1 and ß-catenin. Additionally, BTZ decreased the mRNA expression of claudin-5, occludin, ZO-1, VE-cadherin, and ß-catenin. Our results suggest that BTZ increases the vascular permeability of the pulmonary microvascular endothelium by downregulating cell-cell junction molecules, particularly claudin-5, occludin, and VE-cadherin.

Multicenter propensity score-matched analysis comparing short versus long cap-assisted colonoscopy for acute hematochezia.

Background and Aim: While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes. Methods: We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE-J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy. Results: A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users (P = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users (P < 0.001). The rate of SRH with active bleeding was significantly higher in long cap users (P < 0.001). Other clinical outcomes did not differ significantly. Conclusion: Compared to that with short caps, long cap-assisted colonoscopy is superior for the diagnosis of acute hematochezia, especially CDB, and the identification of active bleeding.

Long-term Risks of Recurrence After Hospital Discharge for Acute Lower Gastrointestinal Bleeding: A Large Nationwide Cohort Study.

BACKGROUND & AIMS: Currently, large, nationwide, long-term follow-up data on acute lower gastrointestinal bleeding (ALGIB) are scarce. We investigated long-term risks of recurrence after hospital discharge for ALGIB using a large multicenter dataset. METHODS: We retrospectively analyzed 5048 patients who were urgently hospitalized for ALGIB at 49 hospitals across Japan (CODE BLUE-J study). Risk factors for the long-term recurrence of ALGIB were analyzed by using competing risk analysis, treating death without rebleeding as a competing risk. RESULTS: Rebleeding occurred in 1304 patients (25.8%) during a mean follow-up period of 31 months. The cumulative incidences of rebleeding at 1 and 5 years were 15.1% and 25.1%, respectively. The mortality risk was significantly higher in patients with out-of-hospital rebleeding episodes than in those without (hazard ratio, 1.42). Of the 30 factors, multivariate analysis showed that shock index ≥1 (subdistribution hazard ratio [SHR], 1.25), blood transfusion (SHR, 1.26), in-hospital rebleeding (SHR, 1.26), colonic diverticular bleeding (SHR, 2.38), and thienopyridine use (SHR, 1.24) were significantly associated with increased rebleeding risk. Multivariate analysis of colonic diverticular bleeding patients showed that blood transfusion (SHR, 1.20), in-hospital rebleeding (SHR, 1.30), and thienopyridine use (SHR, 1.32) were significantly associated with increased rebleeding risk, whereas endoscopic hemostasis (SHR, 0.83) significantly decreased the risk. CONCLUSIONS: These large, nationwide follow-up data highlighted the importance of endoscopic diagnosis and treatment during hospitalization and the assessment of the need for ongoing thienopyridine use to reduce the risk of out-of-hospital rebleeding. This information also aids in the identification of patients at high risk of rebleeding.

Association of T cell infiltration and morphological change of thymus gland with the aggravation of pulmonary emphysema in testosterone deficiency.

Chronic obstructive pulmonary disease is an inflammatory lung disease characterized by chronic bronchitis and emphysema. Our previous study revealed that testosterone depletion induced T cell infiltration in the lungs and aggravated pulmonary emphysema in orchiectomized (ORX) mice exposed to porcine pancreatic elastase (PPE). However, the association between T cell infiltration and emphysema remains unclear. The aim of this study was to determine whether thymus and T cells are involved in the exacerbation of PPE-induced emphysema in ORX mice. The weight of thymus gland in ORX mice was significantly greater than that of sham mice. The pretreatment of anti-CD3 antibody suppressed PPE-induced thymic enlargement and T cell infiltration in the lungs in ORX mice, resulting in improved expansion of the alveolar diameter, a marker of emphysema exacerbation. These results suggest that increased thymic function due to testosterone deficiency and the associated increased pulmonary infiltration of T cells may trigger the development of emphysema.

Prognostic Implications of Urinary Potassium to Creatinine Ratio in Patients With Predialysis Chronic Kidney Disease: A Cohort Study.

OBJECTIVES: Although a low or high serum potassium level in chronic kidney disease (CKD) is associated with worsening renal function and increased cardiovascular disease (CVD) events, urinary potassium excretion has been found to predict adverse health outcomes with conflicting results. We conducted a cohort study to determine whether urinary potassium to creatinine (K/Cr) ratio is an independent risk for further deterioration in renal function or increased CVD events. METHODS: We identified 650 predialysis patients with CKD hospitalized for an educational program regarding CKD between January 2010 and December 2018. The study outcomes were CKD progression and incident CVD events, with baseline urinary K/Cr ratio categorized into quartiles-Q1, < 19.8; Q2, 19.9-27.7; Q3, 27.8-37.9; and Q4, > 38.0. RESULTS: During follow-up (median, 35 months), 509 CKD progressions and 129 incident CVD events were identified. Sixty two patients died during follow-up. Multivariate Cox proportional hazard model showed that after adjustment for demographic factors and laboratory data, patients in Q1 had a 2.02-fold higher risk of worsening renal function than those in Q4 (95% confidence interval, 1.50-2.71; P < .001), whereas urinary K/Cr ratio had no association with the incidence of CVD events. Similarly, inverse probability weighting analysis showed an increased risk of CKD progression in the lowest quartile. Furthermore, the association between low fractional excretion of potassium and worsening renal function was confirmed. CONCLUSION: A low urinary K/Cr ratio is independently associated with worsening renal function but not with a risk of incident CVD event in predialysis patients with CKD.

Outcomes and recurrent bleeding risks of detachable snare and band ligation for colonic diverticular bleeding: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Ligation therapy, including endoscopic detachable snare ligation (EDSL) and endoscopic band ligation (EBL), has emerged as an endoscopic treatment for colonic diverticular bleeding (CDB); its comparative effectiveness and risk of recurrent bleeding remain unclear, however. Our goal was to compare the outcomes of EDSL and EBL in treating CDB and identify risk factors for recurrent bleeding after ligation therapy. METHODS: We reviewed data of 518 patients with CDB who underwent EDSL (n = 77) or EBL (n = 441) in a multicenter cohort study named the Colonic Diverticular Bleeding Leaders Update Evidence From Multicenter Japanese Study (CODE BLUE-J Study). Outcomes were compared by using propensity score matching. Logistic and Cox regression analyses were performed for recurrent bleeding risk, and a competing risk analysis was used to treat death without recurrent bleeding as a competing risk. RESULTS: No significant differences were found between the 2 groups in terms of initial hemostasis, 30-day recurrent bleeding, interventional radiology or surgery requirements, 30-day mortality, blood transfusion volume, length of hospital stay, and adverse events. Sigmoid colon involvement was an independent risk factor for 30-day recurrent bleeding (odds ratio, 1.87; 95% confidence interval, 1.02-3.40; P = .042). History of acute lower GI bleeding (ALGIB) was a significant long-term recurrent bleeding risk factor on Cox regression analysis. A performance status score of 3/4 and history of ALGIB were long-term recurrent bleeding factors on competing risk regression analysis. CONCLUSIONS: There were no significant differences in outcomes between EDSL and EBL for CDB. After ligation therapy, careful follow-up is required, especially in the treatment of sigmoid diverticular bleeding during admission. History of ALGIB and performance status at admission are important risk factors for long-term recurrent bleeding after discharge.

Competition model explains trends of long-term fertilization in plant communities.

Over 40 years ago, Kempton (Biometrics, 35, 1979, 307) reported significant modification to plant community structure following a long-term fertilization experiment. Many researchers have investigated this phenomenon in the years since. Collectively, these studies have shown consistent shifts in rank abundance relationships among species in communities following fertilization. The previous studies indicated that fertilization affects community structure through several critical processes, including trait-based functional response, reordering of species in rank abundance diagram (RAD), and niche dimensionality, although some questions have remained. How does the species reordering driven by the plant responses cause characteristic trends in temporal changes of RAD? Why are those trends ubiquitous in various systems? To answer those questions, we theoretically investigated the effects of fertilization on community structure based on a colonization model (or Levins model) with competition-fecundity trade-offs, which can result in the coexistence of multiple species under competition. The model represents characteristic RAD, which can be an adequate tool to study community composition. Our theoretical model comprehensively represents observed trends in rank abundance relationships following long-term fertilization and suggests that competitive interactions among species are a critical factor in structuring species diversity in plant communities.

Development and validation of a novel model for predicting stigmata of recent hemorrhage in acute lower gastrointestinal bleeding: Multicenter nationwide study.

OBJECTIVES: Stigmata of recent hemorrhage (SRH) directly indicate a need for endoscopic therapy in acute lower gastrointestinal bleeding (LGIB). Colonoscopy would be prioritized for patients with highly suspected SRH, but the predictors of colonic SRH remain unclear. We aimed to construct a predictive model for the efficient detection of SRH using a nationwide cohort. METHODS: We retrospectively analyzed 8360 patients admitted through hospital emergency departments for acute LGIB in the CODE BLUE-J Study (49 hospitals throughout Japan). All patients underwent inpatient colonoscopy. To develop an SRH predictive model, 4863 patients were analyzed. Baseline characteristics, colonoscopic factors (timing, preparation, and devices), and computed tomography (CT) extravasation were extensively assessed. The performance of the model was externally validated in 3497 patients. RESULTS: Colonic SRH was detected in 28% of patients. A novel predictive model for detecting SRH (CS-NEED score: ColonoScopic factors, No abdominal pain, Elevated PT-INR, Extravasation on CT, and DOAC use) showed high performance (area under the receiver operating characteristic curve [AUC] 0.74 for derivation and 0.73 for external validation). This score was also highly predictive of active bleeding (AUC 0.73 for derivation and 0.76 for external validation). Patients with low (0-6), intermediate (7-8), and high (9-12) scores in the external validation cohort had SRH identification rates of 20%, 31%, and 64%, respectively (P < 0.001 for trend). CONCLUSIONS: A novel predictive model for colonic SRH identification (CS-NEED score) can specify colonoscopies likely to achieve endoscopic therapy in acute LGIB. Using the model during initial management would contribute to finding and treating SRH efficiently.

Continuous irregular dynamics with multiple neutral trajectories permit species coexistence in competitive communities.

The colonization model formulates competition among propagules for habitable sites to colonize, which serves as a mechanism enabling coexistence of multiple species. This model traditionally assumes that encounters between propagules and sites occur as mass action events, under which species distribution can eventually reach an equilibrium state with multiple species in a constant environment. To investigate the effects of encounter mode on species diversity, we analyzed community dynamics in the colonization model by varying encounter processes. The analysis indicated that equilibrium is approximately neutrally-stable under perfect ratio-dependent encounter, resulting in temporally continuous variation of species' frequencies with irregular trajectories even under a constant environment. Although the trajectories significantly depend on initial conditions, they are considered to be "strange nonchaotic attractors" (SNAs) rather than chaos from the asymptotic growth rates of displacement. In addition, trajectories with different initial conditions remain different through time, indicating that the system involves an infinite number of SNAs. This analysis presents a novel mechanism for transient dynamics under competition.