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Journal of Food and Drug Analysis Mar 2015To evaluate the efficacy and safety of TNF-α blockers for ulcerative colitis. A systematic search for randomized controlled trials (RCTs) of TNF-α blockers for... (Review)
Review
To evaluate the efficacy and safety of TNF-α blockers for ulcerative colitis. A systematic search for randomized controlled trials (RCTs) of TNF-α blockers for treatment of ulcerative colitis (UC) were performed in PubMed, Web of Science, Embase and cochrane clinical trial. We estimated Pooled estimates of the odds ratio (OR) and relevant 95% confidence interval (CI) using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. Nine randomized controlled studies met the selection criteria with a total of 2518 patients. Five studies compared Infliximab with placebo. Two studies compared Infliximab to corticosteroids. Two studies compared Adalimumab to placebo. One study compared subcutaneous golimumab to placebo. Short-term response, short-term remission, long-term remission and mucosal healing were better in the TNF-α blocker group than in the control group (p < 0.05). TNF-α blockers decreased the colectomy rate and serious adverse reactions (p < 0.05). The TNF-α blockers were superior to controls in achieving short-term clinical response/remission, long-term remission and mucosal healing and decreased the colectomy rate and serious adverse reactions.
PubMed: 28911431
DOI: 10.1016/j.jfda.2014.06.003 -
Journal of Crohn's & Colitis Jan 2020Ustekinumab is approved for the treatment of Crohn's disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the... (Observational Study)
Observational Study
BACKGROUND AND AIMS
Ustekinumab is approved for the treatment of Crohn's disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice.
METHODS
We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission.
RESULTS
In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3-58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response.
CONCLUSION
Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.
Topics: Adult; Cohort Studies; Crohn Disease; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Netherlands; Registries; Treatment Outcome; Ustekinumab
PubMed: 31219157
DOI: 10.1093/ecco-jcc/jjz119 -
Alimentary Pharmacology & Therapeutics Mar 2014Elderly patients represent an increasing proportion of the inflammatory bowel disease (IBD) population. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Elderly patients represent an increasing proportion of the inflammatory bowel disease (IBD) population.
AIM
To critically review available data regarding the care of elderly IBD patients.
METHODS
Bibliographic searches (MEDLINE) up to June 2013.
RESULTS
Approximately 10-15% of cases of IBD are diagnosed in patients aged >60 years, and 10-30% of the IBD population are aged >60 years. In the elderly, IBD is easily confused with other more common diseases, mainly diverticular disease and ischaemic colitis. The clinical features of IBD in older patients are generally similar to those in younger patients. Crohn's disease (CD) in elderly patients is characterised by its predominantly colonic localisation and uncomplicated course. Proctitis and left-sided ulcerative colitis are more common in patients aged >60 years. Infections are associated with age and account for significant mortality in IBD patients. The treatment of IBD in the elderly is generally similar. However, the therapeutic approach in the elderly should be 'start low-go slow'. The benefit of thiopurines in older CD patients remains debatable. Although the indications for anti-tumour necrosis factors in the elderly are generally similar to those for younger patients, lower response and higher adverse events have been reported in the elderly. Surgery in elderly patients does not generally differ. Ileal pouch-anal anastomosis can be successful, provided the patient retains good anal sphincter function.
CONCLUSIONS
Management of the older IBD patient differs from that of younger patients; therefore, conventional practice algorithms may have to be modified to account for advanced age.
Topics: Aged; Humans; Inflammatory Bowel Diseases; Middle Aged
PubMed: 24405149
DOI: 10.1111/apt.12616 -
Analytical Cellular Pathology... 2019Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hepatectomy and liver transplantation (LT) are regarded as the radical treatment, but... (Review)
Review
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hepatectomy and liver transplantation (LT) are regarded as the radical treatment, but great majority of patients are already in advanced stage on the first diagnosis and lose the surgery opportunity. Multifarious image-guided interventional therapies, termed as locoregional ablations, are recommended by various HCC guidelines for the clinical practice. Transarterial chemoembolization (TACE) is firstly recommended for intermediate-stage (Barcelona Clinic Liver Cancer (BCLC) B class) HCC but has lower necrosis rates. Radiofrequency ablation (RFA) is effective in treating HCCs smaller than 3 cm in size. Microwave ablation (MWA) can ablate larger tumor within a shorter time. Combination of TACE with RFA or MWA is effective and promising in treating larger HCC lesions but needs more clinical data to confirm its long-term outcome. The combination of TACE and RFA or MWA against hepatocellular carcinoma needs more clinical data for a better strategy. The characters and advantages of TACE, RFA, MWA, and TACE combined with RFA or MWA are reviewed to provide physician a better background on decision.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Humans; Liver Neoplasms; Microwaves; Radiofrequency Ablation
PubMed: 31534899
DOI: 10.1155/2019/8619096 -
Analytical Cellular Pathology... 2022Acute kidney injury (AKI) is an important public health concern and characterized as tubular death involved in apoptosis and necrosis. Autophagy is rapidly induced in...
Acute kidney injury (AKI) is an important public health concern and characterized as tubular death involved in apoptosis and necrosis. Autophagy is rapidly induced in tubules and associates with renal tubular cells homeostasis to have a complex link with tubular death in AKI. Numb is a multifunctional protein and exerts protective role in tubular death in AKI induced by Cisplatin. However, the effect of Numb on tubular autophagy remains to be investigated. In the present study, the protein expression of LC3 and Beclin-1 related to autophagy was analyzed in Cisplatin-induced AKI mice with knocking down Numb. In model of tubular injury induced by Cisplatin , downregulation of Numb in NRK-52E cells also inhibited the activation of autophagy accompanied with the decreased protein level of p53. Overexpression of Numb in NRK-52E cells activated autophagy with increased LC3 and Beclin-1 expression accompanied with increased protein level of p53. Moreover, autophagy activation following Numb overexpression was suppressed by p53 inhibitor pifithrin-. These data indicate that Numb promotes p53-mediated activation of tubular autophagy in AKI induced by Cisplatin and therefore may provide important targets for the treatment of AKI.
Topics: Acute Kidney Injury; Animals; Autophagy; Beclin-1; Cisplatin; Membrane Proteins; Mice; Tumor Suppressor Protein p53
PubMed: 35795076
DOI: 10.1155/2022/8213683 -
Turk Patoloji Dergisi 2019< strong > Objective: < /strong > Medication resins such as Kayexalate and Sevelamer used in the setting of chronic kidney disease for the correction of hyperkalemia and... (Review)
Review
< strong > Objective: < /strong > Medication resins such as Kayexalate and Sevelamer used in the setting of chronic kidney disease for the correction of hyperkalemia and hyperphosphatemia are associated with gastrointestinal mucosal injury. In this study we describe the clinico-pathological features of Resin-induced gastrointestinal mucosal injury highlighting the histo-morphological appearances and differential diagnoses. The aim of this study is to increase the awareness of pathologists and clinicians alike to an under-reported etiology and pattern of intestinal mucosal injury related to medical resin therapy which may at times pose a clinical emergency. < strong > Material and Method: < /strong > The archives of the Department of Histopathology, Mubarak Al Kabir hospital were analyzed for cases of resin-induced gastrointestinal mucosal injury between 2013 and 2018. < strong > Results: < /strong > Of the 15 cases, Kayexalate crystals were identified in 7 cases, Sevelamer in 5 cases and both together were seen in 3 cases. Resin crystals were identified in the gastric antrum&duodenum (3 cases), colon (9 cases in the left colon, 2 cases in the right colon) and anal canal (1 case). The histological tissue reactions included mucosal necrosis (1 case), inflammatory polyps (2 cases), mucosal ulcerations with granulation tissue formation (10 cases), perforation (1 case) , and luminal crystals (1 case). < strong > Conclusion: < /strong > Accurate and timely recognition of the resin crystals in biopsy samples with clinical correlation is mandatory to avoid serious complications.
Topics: Adult; Aged; Aged, 80 and over; Cation Exchange Resins; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Polystyrenes; Retrospective Studies; Sevelamer
PubMed: 31026044
DOI: 10.5146/tjpath.2018.01458 -
Clinical Gastroenterology and... Jan 2023Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively...
BACKGROUND & AIMS
Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis in the first 2 years after ileal pouch-anal anastomosis and analyze time trends of the incidence of pouchitis.
METHODS
Using national registries, we established a population-based cohort of all Danish patients undergoing proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after surgery, evaluated by time period. We used Kaplan-Meier and Cox proportional hazard modeling to evaluate the time to development of pouchitis.
RESULTS
Overall, 1664 patients underwent an ileal pouch-anal anastomosis. The cumulative incidence of pouchitis in the 2 years after ileal pouch-anal anastomosis increased throughout the study period, from 40% in the period from 1996 to 2000 (95% CI, 35%-46%) to 55% in the period from 2015 to 2018 (95% CI, 48%-63%). Patients undergoing surgery between 2015 and 2018 also showed an increased risk of pouchitis compared with the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (hazard ratio, 1.57; 95% CI, 1.20-2.05).
CONCLUSIONS
This population-based study showed a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis shown in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.
Topics: Humans; Pouchitis; Colitis, Ulcerative; Incidence; Cohort Studies; Proctocolectomy, Restorative; Denmark; Colonic Pouches
PubMed: 35525393
DOI: 10.1016/j.cgh.2022.04.015 -
BioImpacts : BI 2023The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine...
The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1β, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines.
PubMed: 36817000
DOI: 10.34172/bi.2022.23523 -
Journal of Clinical Laboratory Analysis Jul 2022Myocardial infarction (MI) is a serious cardiovascular disease associated with myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine (Dex), an α2-adrenoceptor...
BACKGROUND
Myocardial infarction (MI) is a serious cardiovascular disease associated with myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine (Dex), an α2-adrenoceptor agonist, has been reported to protect against I/R injury. We examined the cardioprotective effects of Dex on cardiomyocytes under hypoxia/reoxygenation (H/R) conditions and explored the underlying mechanisms.
MATERIALS AND METHODS
A H/R model was established to mimic the MI injury. The CCK-8 assay was performed to measure cell viability. Cellular apoptosis was measured using the Annexin V fluorescein isothiocyanate (FITC)-propidium iodide (PI) staining. The levels of interleukin (IL)-1α and tumor necrosis factor (TNF)-α, and the activity of lactate dehydrogenase (LDH) were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Reactive oxygen species (ROS) were measured using the 2'-7' dichlorofluorescein diacetate (DCFH-DA) staining assay. In addition, the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), catalase (CAT), and caspase-3 were measured using a commercial kit. siRNA was used to silence Bcl-2, catalase, or STAT3. Western blotting was used to measure the change in the levels of proteins.
RESULTS
Dex improved the cell viability and inhibited the inflammatory response in H9c2 cells exposed to H/R treatment. In addition, Dex inhibited apoptosis and alleviated the endoplasmic reticulum (ER) stress and oxidative stress in H9c2 cells under the H/R treatment. Mechanism investigation showed that Dex inhibited the intrinsic pathway of apoptosis. Moreover, Dex enhanced the activation of the JAK2/STAT3 signaling pathway in H/R-treated H9c2 cells.
CONCLUSION
Altogether, our findings suggested Dex as a promising therapeutic agent for myocardial I/R.
Topics: Apoptosis; Catalase; Dexmedetomidine; Humans; Hypoxia; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidative Stress
PubMed: 34882841
DOI: 10.1002/jcla.24119 -
Environmental Analysis, Health and... Dec 2022Cypermethrin and dimethoate are pesticides frequently used in agriculture to eliminate pests. Contemporaneity of these and other pesticides in commercial preparations...
Cypermethrin and dimethoate are pesticides frequently used in agriculture to eliminate pests. Contemporaneity of these and other pesticides in commercial preparations and several aquatic ecosystems is well known, though poorly studied. This study aims to evaluate the effect of sublethal concentrations of combinations of cypermethrin and dimethoate on juvenile catfish, Clarias gariepinus, given that the pesticides concomitantly occur in the floodplains were the fish breed. Behavioral, hematological and histopathological changes in juvenile fish exposed to sublethal concentrations were monitored for 96 hours. Pesticide exposed fish exhibited abnormal behaviors such as erratic swimming, frequent air gulping, sudden jerk movement and rapid opercula movement and these were more pronounced in higher concentrations. Significant reductions in erythrocytes (0.83-20.94%), hemoglobin (4.12-29.23%) and PVC (7.14-28.57%) and increase in leucocytes (4.84-9.32%) were observed (p<0.05). Mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH) and mean cell volume (MCV) reduced significantly in the exposed groups compared to the control. Infiltration of inflammatory cells, distortion of cell architecture, hemorrhage and necrosis were the observed histopathological damages in the heart, brain, gill, liver, kidney and fin of exposed fish. These pathological damages were more severe than previously reported for either chemical. Therefore, the use of these chemicals in agriculture should be regulated, especially near fish breeding sites.
PubMed: 36916041
DOI: 10.5620/eaht.2022028