Relationship between Ustekinumab trough concentrations and clinical, biochemical and endoscopic outcomes in Crohn's disease: A multi-center nationwide retrospective study (TARGET STUDY).

Ustekinumab has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real-life. We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6 mg/kg intravenous induction followed by 90 mg every 4-, 8-, or 12-weeks during maintenance were included. We assessed clinical, biochemical, and endoscopic outcomes. Trough concentrations of ustekinumab that were taken from week 42 to week 52 were measured. Primary outcome was to evaluate the relationship between ustekinumab trough concentrations and clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes. A total of 137 patients with CD, median age of 32 years and 83 (60.6%) males. The median serum levels of ustekinumab measured was 7.2 mcg/mL (interquartile range [IQR] 3.1-9.6). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and simple endoscopic score (SES-CD) (r = -0.464, P < .001). Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by Harvey-Bradshaw index (HBI) score (r = -0.582, P < .001), C-Reactive Protein (CRP) levels (r = -0.598, P < .001) and fecal calprotectin (FC) levels (r = -0.529, P < .001). A multivariable analysis adjusted for age, sex and body mass index (BMI) showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/mL was associated with 24% increase in the likelihood of having an SES-CD score <3 (OR 1.24, confidence interval [CI] 1.12-1.37, P value < .001), 44% more likely to achieve HBI score <5 (OR 1.44, CI 1.26-1.65, P value < .001), 52% higher likelihood of CRP more than 10 (OR 1.52, CI 1.31-1.77, P < .001), and 42% increased likelihood of FC more than 250 (OR 1.42, CI 1.24-1.62, P < .001). Ustekinumab trough concentrations above 4.5 mcg/mL were associated with clinical, biochemical and endoscopic remission in CD. Prospective data is warranted to confirm these findings.

The potential for medical therapies to address fistulizing Crohn's disease: a state-of-the-art review.

INTRODUCTION: Crohn's disease (CD) is a chronic, relapsing immune mediated disease, which is one of the two major types of inflammatory bowel disease (IBD). Fistulizing CD poses a significant clinical challenge for physicians. Effective management of CD requires a multidisciplinary approach, involving a gastroenterologist and a GI surgeon while tailoring treatment to each patient's unique risk factors, clinical representations, and preferences. AREAS COVERED: This comprehensive review explores the intricacies of fistulizing CD including its manifestations, types, impact on quality of life, management strategies, and novel therapies under investigation. EXPERT OPINION: Antibiotics are often used as first-line therapy to treat symptoms. Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials. However, more than 50% of patients lose response to IFX, prompting them to explore alternative strategies. Current options include adalimumab and certolizumab pegol combination therapies, as well as small-molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas is mesenchymal stem cells such as Darvadstrocel (Alofisel), an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options.

High-Performance Porous Organic Polymers for Environmental Remediation of Toxic Gases.

Sulfur dioxide (SO2) is a harmful acidic gas generated from power plants and fossil fuel combustion and represents a significant health risk and threat to the environment. Benzimidazole-linked polymers (BILPs) have emerged as a promising class of porous solid adsorbents for toxic gases because of their chemical and thermal stability as well as the chemical nature of the imidazole moiety. The performance of BILPs in SO2 capture was examined by synergistic experimental and theoretical studies. BILPs exhibit a significantly high SO2 uptake of up to 8.5 mmol g-1 at 298 K and 1.0 bar. The density functional theory (DFT) calculations predict that this high SO2 uptake is due to the dipole-dipole interactions between SO2 and the functionalized polymer frames through O2S(δ+)···N(δ-)-imine and O═S═O(δ-)···H(δ+)-aryl and intermolecular attraction between SO2 molecules (O═S═O(δ-)···S(δ+)O2). Moderate isosteric heats of adsorption (Qst ≈ 38 kJ mol-1) obtained from experimental SO2 uptake studies are well supported by the DFT calculations (≈40 kJ mol-1), which suggests physisorption processes enabling rapid adsorbent regeneration for reuse. Repeated adsorption experiments with almost identical SO2 uptake confirm the easy regeneration and robustness of BILPs. Moreover, BILPs possess very high SO2 adsorption selectivity at low concentration over carbon dioxide (CO2), methane (CH4), and nitrogen (N2): SO2/CO2, 19-24; SO2/CH4, 118-113; SO2/N2, 600-674. This study highlights the potential of BILPs in the desulfurization of flue gas or other gas mixtures through capturing trace levels of SO2.

Immunogenicity of Hepatitis B Vaccination in Patients with Ulcerative Colitis on Infliximab Is Attenuated Compared to Those on 5-Aminosalicylic Acid Therapies: A Prospective Observational Study.

INTRODUCTION: Hepatitis B virus (HBV) infection has been associated with chronic hepatitis and cirrhosis. Patients with inflammatory bowel disease (IBD) may be at a higher risk of HBV infection reactivation, especially those on biologic therapies. This study intends to compare the effectiveness of the HBV vaccine in patients with ulcerative colitis (UC) on infliximab (IFX) compared to those on 5-aminosalicylic acid (5-ASA). METHODS: Patients with UC aged >18 years old were prospectively enrolled in the study. The patients were divided into two groups: patients treated with 5-ASA (control group) and patients treated with IFX (study group). HBV vaccination was administered (20 mcg) following the standard regimen, and Hepatitis B serum antibody (HbsAb) titers were assessed three months after the final dose. The response to HBV vaccines was categorized as an 'adequate' immune response (≥10 IU/L) and 'effective' immune response (≥100 IU/L). RESULTS: In our final analysis of 118 patients with UC, 54.2% were male and 52.5% had extensive colitis. HBsAb titer levels were significantly higher in the 5-ASA group (126.7 ± 37.5) compared to the IFX group (55.5 ± 29.4). Stratifying HBsAb levels into two categories (≥10-99 IU/L and ≥100 IU/L) revealed a significantly greater proportion of subjects in the 5-ASA group with levels ≥100 IU/L compared to the IFX group (76.7% vs. 12.1%, p < 0.001). Logistic regression analysis demonstrated that patients with UC receiving 5-ASA were 23.94 times more likely to exhibit HBsAb levels ≥ 100 compared to those treated with IFX (OR = 23.94, 95% CI 8.89-64.49). CONCLUSION: The immune response to hepatitis B vaccination in patients with ulcerative colitis treated with IFX is attenuated compared to those treated with 5-ASA. Therefore, emphasizing the importance of HBV vaccination for patients with IBD before starting anti-TNF therapy, especially IFX, and advocating for screening is imperative in high-risk countries. Determining what levels of HBsAb provide protection and what happens to the levels over time after a booster dose are important clinical questions to be answered by follow-up studies.

Accuracy and Feasibility of Using a Smartphone Application for Carbohydrate Counting Versus Traditional Carbohydrate Counting for Adults With Insulin-Treated Diabetes.

BACKGROUND: Patients with insulin-treated diabetes struggle with performing accurate carbohydrate counting for proper blood glucose control. Little is known about the comparative accuracy and feasibility of carbohydrate counting methods. PURPOSE: The purpose of this study was to determine whether carbohydrate counting using a smartphone application is more accurate and feasible than a traditional method. THEORETICAL/CONCEPTUAL FRAMEWORK: Based on a conceptual model derived from the Technology Acceptance Model, feasibility was defined as usefulness, ease of use, and behavioral intention to use each method. METHODS: A standardized meal was presented to 20 adults with insulin-treated diabetes who counted carbohydrates using traditional and smartphone methods. Accuracy was measured by comparing carbohydrate counting estimates with the standardized meal values. Perceived feasibility (usefulness, ease of use, behavioral intention) was measured using rating forms derived from the Technology Acceptance Model. RESULTS: The number of training and estimation minutes were significantly higher for the traditional method than the smartphone method (Z = -3.83, P < .05; Z = -2.30, P < .05). The traditional method took an additional 1.4 minutes for estimation and 12.5 minutes for training. There were no significant differences in accuracy between traditional and smartphone methods for carbohydrate counting (Wilcoxon signed-rank test, Z = -1.10, P = .28). There were no significant differences between traditional and smartphone methods for feasibility (usefulness, Z = -.10, P = .95; ease of use, Z = -.36, P = .72; or behavioral intention, Z = -.94, P = .35). CONCLUSION: While both traditional and smartphone methods were found to be similar in terms of accuracy and feasibility, the smartphone method took less time for training and for carbohydrate estimation.

High Sodium Ion Storage by Multifunctional Covalent Organic Frameworks for Sustainable Sodium Batteries.

Rechargeable sodium batteries hold great promise for circumventing the increasing demand for lithium-ion batteries (LIBs) and the limited supply of lithium. However, efficient sodium ion storage remains a great impediment in this field. In this study, we report the designed synthesis of a multifunctional two-dimensional covalent organic framework featuring hexaazatrinaphthalene cores linked by imidazole moieties and demonstrate its effective performance in sodium ion storage. Benzimidazole-linked covalent organic framework (BCOF-1) was synthesized by a condensation reaction between hexaazatrinaphthalenehexamine (HATNHA) and terephthalaldehyde (TA) and exhibited a high theoretical specific capacity of 392 mA h g-1. BCOF-1 crystallizes, forming eclipsed AA stacking and mesoporous hexagonal one-dimensional channels with high surface area (840 m2 g-1), facilitating fast ionic mobility and charge transfer and enabling high-rate capability at high current rates. BCOF-1 exhibits pseudocapacitive-like behavior with a high specific capacity of 387 mA h g-1, an energy density of 302 W h kg-1 at 0.1 C, and a power density of 682 W kg-1 at 5 C. Our results demonstrate that redox-active COFs have the desired structural and electronic merits to advance the use of organic electrodes in sodium-ion storage toward sustainable and efficient batteries.

Selective Reduction of Multivariate Metal-Organic Frameworks for Advanced Electrocatalytic Cathodes in High Areal Capacity and Long-Life Lithium-Sulfur Batteries.

Lithium-sulfur batteries hold great promise as next-generation high-energy-density batteries. However, their performance has been limited by the low cycling stability and sulfur utilization. Herein, we demonstrate that a selective reduction of the multivariate metal-organic framework, MTV-MOF-74 (Co, Ni, Fe), transforms the framework into a porous carbon decorated with bimetallic CoNi alloy and Fe3O4 nanoparticles capable of entrapping soluble lithium polysulfides while synergistically facilitating their rapid conversion into Li2S. Electrochemical studies on coin cells containing 89 wt % sulfur loading revealed a reversible capacity of 1439.8 mA h g-1 at 0.05 C and prolonged cycling stability for 1000 cycles at 1 C/1060.2 mA h g-1 with a decay rate of 0.018% per cycle. At a high areal sulfur loading of 6.9 mg cm-2 and lean electrolyte/sulfur ratio (4.5 µL:1.0 mg), the battery based on the 89S@CoNiFe3O4/PC cathode provides a high areal capacity of 6.7 mA h cm-2. The battery exhibits an outstanding power density of 849 W kg-1 at 5 C and delivers a specific energy of 216 W h kg-1 at 2 C, corresponding to a specific power of 433 W kg-1. Density functional theory shows that the observed results are due to the strong interaction between the CoNi alloy and Fe3O4, facilitated by charge transfer between the polysulfides and the substrate.

Histological Disease Activity as Predictor of Clinical Relapse, Hospitalization, and Surgery in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND: The clinical impact of histological remission on short- and long-term clinical outcomes in patients with inflammatory bowel disease (IBD) is not well established. We assessed risk of clinical relapse, hospitalization, and need for surgery in patients achieving histological remission in comparison with active histological disease. METHODS: A systematic review was conducted using MEDLINE, Scopus, Cochrane CENTRAL, EMBASE, and conference abstracts from inception to November 2022. Our main outcome was the rate of clinical relapse in patients with IBD who reached histological remission vs patients with active histological disease. Secondary outcomes were clinical complications of IBD such as hospitalization and need for surgery. The endpoints were investigated at 2 time points, 6 to 12 months (short term) and >12 months (long term). RESULTS: Short-term outcome analysis showed that the risk of clinical relapse was significantly higher in ulcerative colitis patients with active histological disease in comparison with patients at histological remission (risk ratio [RR], 2.41; 95% confidence interval [CI], 1.69-3.44; P < .01). The risk of hospitalization in ulcerative colitis patients was not significant among the 2 groups (RR, 4.22; 95% CI, 0.91-19.62; P = .07). Long-term outcome analysis demonstrated that the risk of clinical relapse (RR, 2.07; 95% CI, 1.55-2.76; P < .01), need for surgery (RR, 3.14; 95% CI, 1.53-6.45; P < .01), and hospitalization (RR, 2.52; 95% CI, 1.59-4.00; P < .01) was significantly higher in patients with active histological disease. CONCLUSIONS: Histological remission in IBD represents an important therapeutic goal that is not yet routinely pursued in clinical practice. In our study, patients who achieved histological remission have more favorable outcomes than those with active histological disease in ulcerative colitis.

Upadacitinib as a Rescue Therapy in Acute Severe Ulcerative Colitis: A Case Report and Review of the Literature.

BACKGROUND Ulcerative colitis (UC) is a chronic immune-mediated disease of the colon. The mainstay of treatment to achieve and maintain remission is 5-aminosalicylic acid (5-ASA). At least 20% of patients with UC experience an acute severe ulcerative colitis (ASUC) flare, requiring aggressive early intervention to prevent complications. The first-line treatment of ASUC is intravenous steroids followed by infliximab or cyclosporin in patients for whom steroids fail. Refractory disease failing medical therapy and warranting surgery is common. Lately, Janus kinase (JAK) inhibitors, such as tofacitinib, filgotinib, and upadacitinib, have been licensed for moderate-to-severe UC in adults. Nevertheless, the safety and efficacy of upadacitinib in ASUC has not yet been established. CASE REPORT We report a case of an 18-year-old woman with 4-year history of severe UC. Both infliximab and adalimumab treatments failed, despite the concurrent use of azathioprine, and she was reliant on steroids. Moreover, tofacitinib failed after 1 year of therapy. She was admitted as a case of ASUC. Flexible sigmoidoscopy confirmed severe pancolitis. Finally, she was treated effectively with oral upadacitinib 45 mg given once daily. She went into full clinical, biochemical, and steroid-free remission in 60 days and endoscopic remission at 180 days. CONCLUSIONS This case report features the potential safety and efficacy of upadacitinib in adults with ASUC. Larger trials are required to confirm the efficacy and safety in patients admitted with ASUC.

The Proinflammatory Role of ANGPTL8 R59W Variant in Modulating Inflammation through NF-κB Signaling Pathway under TNFα Stimulation.

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is known to regulate lipid metabolism and inflammation. It interacts with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity and with IKK to modulate NF-κB activity. Further, a single nucleotide polymorphism (SNP) leading to the ANGPTL8 R59W variant associates with reduced low-density lipoprotein/high-density lipoprotein (LDL/HDL) and increased fasting blood glucose (FBG) in Hispanic and Arab individuals, respectively. In this study, we investigate the impact of the R59W variant on the inflammatory activity of ANGPTL8. METHODS: The ANGPTL8 R59W variant was genotyped in a discovery cohort of 867 Arab individuals from Kuwait. Plasma levels of ANGPTL8 and inflammatory markers were measured and tested for associations with the genotype; the associations were tested for replication in an independent cohort of 278 Arab individuals. Impact of the ANGPTL8 R59W variant on NF-κB activity was examined using approaches including overexpression, luciferase assay, and structural modeling of binding dynamics. RESULTS: The ANGPTL8 R59W variant was associated with increased circulatory levels of tumor necrosis factor alpha (TNFα) and interleukin 7 (IL7). Our in vitro studies using HepG2 cells revealed an increased phosphorylation of key inflammatory proteins of the NF-κB pathway in individuals with the R59W variant as compared to those with the wild type, and TNFα stimulation further elevated it. This finding was substantiated by increased luciferase activity of NF-κB p65 with the R59W variant. Modeled structural and binding variation due to R59W change in ANGPTL8 agreed with the observed increase in NF-κB activity. CONCLUSION: ANGPTL8 R59W is associated with increased circulatory TNFα, IL7, and NF-κB p65 activity. Weak transient binding of the ANGPTL8 R59W variant explains its regulatory role on the NF-κB pathway and inflammation.

Effectiveness of vedolizumab and ustekinumab as second biologic agent in achieving target outcomes in tumor necrosis factor antagonists experienced patients with inflammatory bowel disease (enroll-ex study).

Background: About a third of patients with inflammatory bowel disease (IBD) do not respond to anti-tumor necrosis factor (anti-TNF) therapy. In our study, we evaluated the effectiveness of vedolizumab and ustekinumab in achieving clinical and endoscopic outcomes in anti-TNF-experienced patients with IBD. Methods: We conducted a retrospective cohort study. Electronic medical records of patients with moderate to severe IBD, who were previously received anti-TNF therapies, were reviewed and evaluated retrospectively in a gastroenterology center. Outcomes of patients treated with ustekinumab or vedolizumab after failing one anti-TNF agent were evaluated. The primary outcomes were the percentage of hospitalization, surgery, mucosal healing and steroid-free remission. Mucosal healing was defined as a Mayo endoscopic score of 0 or 1 in ulcerative colitis (UC) and an SES-CD score of less than 3 in Crohn's disease (CD). Outcomes were quantified using descriptive analysis. Results: A total of 207 (130 CD: 77 UC) patients with IBD who had previously received one anti-TNF agent were included in the study. Of the total cohort, 62 (30.0%) patients were receiving vedolizumab, and 145 (70.0%) patients were on ustekinumab. 101 (77.6%) patients with CD who failed one anti-TNF therapy were on ustekinumab. Of these patients, 26 (19.7%) patients were hospitalized, and 12 (11.9%) patients had IBD-related surgery. 16 (16.1%) patients had at least one corticosteroid course. 60 (59.0%) patients with CD on ustekinumab achieved mucosal healing. 29 (22.3%) patients with CD who failed one anti-TNF therapy were receiving vedolizumab. Of those, 7 (25%) patients were hospitalized, and 11 (37.9%) patients had IBD-related surgery. 15 (51.0%) patients achieved mucosal healing. 44 (57.1%) patients with UC who failed one anti-TNF therapy were on ustekinumab. Of these 6 (14.1%) patients were hospitalized, 3 (7.0%) patients had IBD-related surgery and 13 (30%) patients had at least 1 corticosteroid course. 25 (57.0%) patients achieved mucosal healing. 33 (42.8%) patients with UC who failed one anti-TNF therapy were receiving vedolizumab. Of those, 6 (18.6%) patients were hospitalized, and 16 (49.6%) patients had at least 1 corticosteroid course. 17 (53.2%) patients achieved mucosal healing. Conclusion: Ustekinumab and vedolizumab were both effective in achieving clinical outcomes in patients with IBD after failing an anti-TNF agent. However, patients receiving ustekinumab had numerically higher percentages of reaching target outcomes than patients receiving vedolizumab. A prospective head-to-head trial is warranted to confirm these findings.

Postsynthetic Modification of Core-Shell Magnetic Covalent Organic Frameworks for the Selective Removal of Mercury.

Core-shell magnetic covalent organic framework (COF) materials were prepared, followed by shell material functionalization with different organic ligands, including thiosemicarbazide, through a postsynthetic modification approach. The structures of the prepared samples were characterized with various techniques, including powder X-ray diffraction (PXRD), Brunauer-Emmett-Teller (BET) method, thermogravimetric analysis (TGA), photoinduced force microscopy (PiFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and solid 13C NMR. PXRD and BET studies revealed that the crystalline and porous nature of the functionalized COFs was well maintained after three steps of postsynthetic modification. On the other hand, solid 13C NMR, TGA, and PiFM analyses confirmed the successful functionalization of COF materials with good covalent linkage connectivity. The use of the resulting functionalized magnetic COF for selective and ultrafast adsorption of Hg(II) has been investigated. The observations displayed rapid kinetics with adsorption dynamics conforming to the quasi-second-order kinetic model and the Langmuir adsorption model. Furthermore, this prepared crystalline magnetic material demonstrated a high Langmuir Hg(II) uptake capacity, reaching equilibrium in only 5 min. Thermodynamic calculations proved that the adsorption process is endothermic and spontaneous.

Exploring the Pipeline of Novel Therapies for Inflammatory Bowel Disease; State of the Art Review.

Crohn's disease (CD) and ulcerative colitis (UC), known as inflammatory bowel diseases (IBD), are characterized by chronic inflammation of the gastrointestinal tract. Over the last two decades, numerous medications have been developed and repurposed to induce and maintain remission in IBD patients. Despite the approval of multiple drugs, the major recurring issues continue to be primary non-response and secondary loss of response, as well as short- and long-term adverse events. Most clinical trials show percentages of response under 60%, possibly as a consequence of strict inclusion criteria and definitions of response. That is why these percentages appear to be more optimistic in real-life studies. A therapeutic ceiling has been used as a term to define this invisible bar that has not been crossed by any drug yet. This review highlights novel therapeutic target agents in phases II and III of development, such as sphingosine-1-phosphate receptor modulators, selective Janus kinase inhibitors, anti-interleukins, and other small molecules that are currently under research until 1 January 2023. Emerging treatments for CD and UC that have just received approval or are undergoing phase III clinical trials are also discussed in this review.

Impact of biologic therapies and small molecules on the risk of major adverse cardiovascular events in patients with inflammatory bowel diseases: systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The aim of this study is to estimate the risk of major adverse cardiovascular events (MACEs) in adult patients with inflammatory bowel disease (IBD) treated with biologic therapies and small molecules. METHODS: Databases were searched up to July 2022 to identify eligible studies that assessed the risk of MACEs in patients (age≥18 years) with IBD treated with biologic therapies and small molecules. Primary outcome was the rate of MACEs observed in patients receiving biologic or small molecules therapies during induction and maintenance phases of RCTs. RESULTS: In total 64 studies were included in the analysis. 22 RCTs involving 12,196 patients with Crohn's disease (CD) were included and 32 RCTs involving 22,007 patients with ulcerative colitis (UC). In patients with CD, risk of MACE was not higher than placebo during induction or maintenance phases, infliximab (OR 0.63, 95% CI 0.07-6.14) and ustekinumab (OR 0.50, 95% CI 0.03-8.04). In patients with UC, risk of MACE was not higher than placebo, tofacitinib (OR 1.30, 95% CI 0.15-11.21) and upadcitinib (OR 0.50, 95% CI 0.03-7.97) during induction or maintenance. CONCLUSION: The use of biologic therapies and small molecules among adult patients with IBD had no significant impact on the risk of MACEs during induction and maintenance period of RCTs. Real world data is warranted to assess long-term risks.

Biologic and new small molecule therapies have been shown to be effective in treating patients with moderate to severe inflammatory bowel disease (IBD), both Crohn's disease and ulcerative colitis. The risk of major adverse cardiovascular events (MACE), such as heart attack or heart failure, due to taking these medications in patients with IBD is not well established. The aim of this systematic review and meta-analysis is to estimate the risk of MACE in patients with IBD on biologic or small molecule therapies during induction and maintenance phases of randomized controlled trials. [Figure: see text].

Gradient-Based Optimizer (GBO): A Review, Theory, Variants, and Applications.

This paper introduces a comprehensive survey of a new population-based algorithm so-called gradient-based optimizer (GBO) and analyzes its major features. GBO considers as one of the most effective optimization algorithm where it was utilized in different problems and domains, successfully. This review introduces set of related works of GBO where distributed into; GBO variants, GBO applications, and evaluate the efficiency of GBO compared with other metaheuristic algorithms. Finally, the conclusions concentrate on the existing work on GBO, showing its disadvantages, and propose future works. The review paper will be helpful for the researchers and practitioners of GBO belonging to a wide range of audiences from the domains of optimization, engineering, medical, data mining and clustering. As well, it is wealthy in research on health, environment and public safety. Also, it will aid those who are interested by providing them with potential future research.

Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn's Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD. METHODS: We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55). CONCLUSIONS: Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.

Despite the era of biologic therapies, the management of fistulizing Crohn's disease remains challenging. This is the first systematic review and network meta-analysis to compare the efficacy of biologic therapies in inducing response and remission in patients with fistulizing Crohn's disease. We found that anti-tumor necrosis factor agents are effective in inducing response and remission. Infliximab was superior to adalimumab for inducing response but not for inducing remission.

A Comprehensive Review of Bat Inspired Algorithm: Variants, Applications, and Hybridization.

Bat algorithm (BA) is one of the promising metaheuristic algorithms. It proved its efficiency in dealing with various optimization problems in diverse fields, such as power and energy systems, economic load dispatch problems, engineering design, image processing and medical applications. Thus, this review introduces a comprehensive and exhaustive review of the BA, as well as evaluates its main characteristics by comparing it with other optimization algorithms. The review paper highlights the performance of BA in different applications and the modifications that have been conducted by researchers (i.e., variants of BA). At the end, the conclusions focus on the current work on BA, highlighting its weaknesses, and suggest possible future research directions. The review paper will be helpful for the researchers and practitioners of BA belonging to a wide range of audiences from the domains of optimization, engineering, medical, data mining and clustering. As well, it is wealthy in research on health, environment and public safety. Also, it will aid those who are interested by providing them with potential future research.

Templated Synthesis of 2D Polyimide Covalent Organic Framework for Rechargeable Sodium-Ion Batteries.

Covalent organic frameworks (COFs) hold great promise for electrochemical energy storage because of their high surface area, readily accessible redox-active sites, and environment-friendly chemical composition. In this study, the synthesis of a redox-active pyrene-containing polyimide COF (PICOF-1) by linker exchange using an imine-linked COF as a template is reported and its performance in sodium-ion batteries (SIBs) is demonstrated. The reported synthetic route based on linker exchange mitigates the challenges typically encountered with crystallizing chemically stable polyimide COFs from typical condensation reactions; thus, facilitating their rapid synthesis and purification. Using this approach, PICOF-1 exhibits high crystallinity with very low refinement parameters RP and RWP of 0.415% and 0.326%, respectively. PICOF-1 has a high Brunauer-Emmette-Teller (BET) surface area of 924 m2  g-1 and well-defined one-dimentional (1D) channels of 2.46 × 1.90 nm, which enable fast ion transport and charge transfer, reaching a capacity at 0.1 C of almost nearly as its theoretical capacity and maintaining 99% Coulombic efficiency over 175 cycles at 0.3 C. The study demonstrates that imine-linked COFs are effective templates for integrating carbonyl-rich polyimide moieties into high-surface COFs to advance electrochemical energy storage applications.

Biologic Therapies for the Treatment of Post-ileal Pouch Anal Anastomosis Surgery Chronic Inflammatory Disorders: Systematic Review and Meta-analysis.

Background: Chronic inflammatory disorders after ileal pouch-anal anastomosis (IPAA) surgery are common. These include chronic pouchitis (CP), Crohn's disease (CD) of the pouch, prepouch ileitis (PI) and rectal cuff inflammation (cuffitis). The aim of this study was to evaluate the efficacy of biologic therapies in treating these disorders. Method: Systematic review of all published studies from inception to August 1, 2021 was performed to investigate the efficacy of biologic therapies for post-IPAA chronic inflammatory disorders. The primary outcome was the efficacy of biologic therapies in achieving complete clinical response in patients with IPAA. Results: A total of 26 studies were identified including 741 patients. Using a random-effect model, the efficacy of infliximab in achieving complete clinical response in patients with CP was 51% (95% CI, 36 to 66), whereas the efficacy of adalimumab was 47% (95% CI, 31 to 64). The efficacies of ustekinumab and vedolizumab were 41% (95% CI, 06 to 88) and 63% (95% CI, 35 to 84), respectively. In patients with CD/PI, the efficacy of infliximab in achieving complete clinical response was 52% (95% CI, 33 to 71), whereas the efficacy of adalimumab was 51% (95% CI, 40 to 61). The efficacies of ustekinumab and vedolizumab were 42% (95% CI, 06 to 90) and 67% (95% CI, 38 to 87), respectively. Only one study involved patients with cuffitis. Conclusion: Ustekinumab, infliximab, vedolizumab and adalimumab are effective in achieving complete clinical response in post-IPAA surgery chronic inflammatory disorders. More studies are needed to determine the efficacy of biologics in cuffitis.

Effectiveness of Dual Biologic or Small Molecule Therapy for Achieving Endoscopic Remission in Refractory Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic autoimmune disease with relapse-remission courses. A number of patients may present with a refractory disease with partial or no response to treatment. Others may present with extra-intestinal manifestations that makes the treatment with one biologic challenging. Dual target therapy (DTT), combining biologics and/or small molecule drugs, may offer a chance to achieve remission in these cases and improve patients' quality of life despite the limited evidence regarding this approach. We present a case series of refractory inflammatory bowel disease cases managed with DTT. Seven patients with refractory IBD achieved steroid free, clinical, and endoscopic remission by using DTT. These results support that DTT could be an effective approach in selected patients with refractory IBD or with concomitant extra-intestinal manifestations (EIM). Larger studies, ideally randomized controlled trials, are needed to further support the evidence and confirm the efficacy and safety of DTT for IBD.