Intestinal complications in Brazilian patients with ulcerative colitis treated with conventional therapy between 2011 and 2020

BACKGROUND This was an observational, descriptive, and retrospective study from 2011 to 2020 from the Department of Informatics of the Brazilian Healthcare System database.AIM To describe the intestinal complications(IC) of patients with ulcerative colitis(UC) who started conventional therapies in Brazil’s public Healthcare system.METHODS Patients ≥ 18 years of age who had at least one claim related to UC 10th revision of the International Statistical Classification of Diseases and Related Health Problems(ICD-10) code and at least 2 claims for conventional therapies were included. IC was defined as at least one claim of: UC-related hospitalization, procedures code for rectum or intestinal surgeries, and/or associated disease defined by ICD-10 codes(malignant neoplasia of colon, stenosis, hemorrhage, ulcer and other rectum or anus disease, megacolon, functional diarrhea volvulus, intussusception and erythema nodosum). Descriptive statistics, annual incidence, and incidence rate(IR) [per 100 patient-years(PY)] over the available follow-up period were calculated.RESULTS In total, 41229 UC patients were included(median age, 48 years;65% women) and the median(interquartile range) follow-up period was 3.3(1.8-5.3) years. Conventional therapy used during follow-up period included: mesalazine(87%), sulfasalazine(15%), azathioprine(16%) or methotrexate(1%) with a median duration of 1.9(0.8-4.0) years. Overall IR of IC was 3.2 cases per 100 PY. Among the IC claims, 54% were related to associated diseases, 20% to procedures and 26% to hospitalizations. The overall annual incidence of IC was 2.9%, 2.6% and 2.5% in the first, second and third year after the first claim for therapy(index date), respectively. Over the first 3 years, the annual IR of UC-related hospitalizations ranged from 0.8% to 1.1%;associated diseases from 0.9% to 1.2%-in which anus or rectum disease, and malignant neoplasia of colon were the most frequently reported;and procedure events from 0.6% to 0.7%, being intestinal resection and polyp removal the most frequent ones.CONCLUSION Study shows that UC patients under conventional therapy seem to present progression of disease developing some IC, which may have a negative impact on patients and the burden on the health system.

Effectiveness of topical oxygen therapy in wound healing for patients with diabetic foot ulcer

Objectives:Non-healing wounds have been one of the major challenges in health care because of increased morbidity,especially for those who have diabetes mellitus.Numerous regimens are being innovated to produce an evidence-based practice that would minimize complications and promote healing.Topical oxygen therapy is an innovation in wound care that has been considered influential in the wound healing process.This intervention aims to increase the oxygen concentration in the affected limb to promote wound healing.Methods:This research applied an experimental design that targeted a total of 60 adult patients aged 45–64 years with diabetic foot ulcers.A randomized systematic sampling technique was used to allow equal chances and prevent bias.In total,30 patients in the control group received usual care for diabetic foot ulcers,and the remaining 30 patients in the experimental group received topical oxygen therapy together with standard care for diabetic foot ulcers.Subjects were assessed using the Wagner-Meggitt Wound Classification System.Results:The result proved that there was a significant difference in the wound grade of patients in the experimental group after the application of the usual wound care plus the topical oxygen therapy using Friedman's test.The control and experimental groups were compared using Mann–Whitney statistical analyses,and the results showed that there was a significant difference between the control and experimental groups after the application of topical oxygen therapy.Conclusions:Topical oxygen therapy was demonstrated to be effective to aid in the wound healing process of patients with diabetic foot ulcers.Fur ther research was recommended to improve the application of topical oxygen therapy to patients with chronic wounds and promote the wound healing process.

Discontinuation of therapy in inflammatory bowel disease: Current views

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.

Clinical effects of psychological intervention and drug therapy against peptic ulcer

Objective:To evaluate the clinical effects of psychological interventions and drug therapy against peptic ulcer.Methods:96 patients with peptic ulcer were divided into control group with Tagamet 800 mg per evening p.o.and trial group with psychological intervention on the basis of drug treatment.Results:There were significant differences between the two groups(P【0.05), the trial group showed that the anxiety and depression cases declined obviously and effective rate of ulcer therapy was much higlier than control group.Conclusions:In sum,psychological intervention combined with drug therapy provides an effective method for ulcer treatment.

Current medical therapy for ulcerative colitis

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Promising biological therapies for ulcerative colitis: A review of the literature

Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.

Does physical therapy and rehabilitation improve outcomes for diabetic foot ulcers?

One of the most common and serious complications of diabetes mellitus is ulceration of the foot. Among persons with diabetes, 12%-25% will present to a healthcare institution for a foot disorder during their lifespan. Despite currently available medical and surgical treatments, these are still the most common diabetes-related cause of hospitalization and of lower extremity amputations. Thus, many adjunctive and complementary treatments have been developed in an attempt to improve outcomes. We herein review the available literature on the effectiveness of several treatments, including superficial and deep heaters, electro-therapy procedures, prophylactic methods, exercise and shoe modifications, on diabetic foot wounds. Overall, although physical therapy modalities seem to be useful in the treatment of diabetic foot wounds, further randomized clinical studies are required.

Epinephrine injection therapy versus a combination of epinepnrine injection and endoscopic hemoclip in the treatment of bleeding ulcers

AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone.METHODS: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied.RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different.CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.

Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.

Treatment of diabetic foot ulcer with medicinal leech therapy and honey curcumin dressing: a case report

Background:Diabetic foot ulcers(DFUs)are common in patients with diabetes.The mortality rate of DFUs is ranked the highest after cancer.With advancements in modern medicine,leech therapy,a traditional treatment method for chronic wounds in Iranian medicine,has proven effective in relieving venous congestion.Herein,we aimed to observe the curative effects of leech therapy in combination with honey and curcumin dressing in a 77-year-old patient with a diabetic foot ulcer(UFC).Methods:Two medium-sized medicinal leeches were placed surrounding a grade 2 wound,based on Wagner’s classification system,located on the right first toe.The patient reported a visual analogue scale(VAS)score of 8.After leech therapy,the wound was covered with honey and curcumin,followed by oral administration of ciprofloxacin for 10 days.Results:Pain increased immediately after leech therapy(VAS:9-10)but decreased significantly(VAS:6)2 days after the therapy.At the end of the 2nd day,pain completely disappeared.After 3 weeks,there was no wound on the toe.After 12 weeks,there were no traces of the wound.Conclusion:Leech therapy in combination with honey and curcumin dressing is effective against disease progression in patients with DFUs.

Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer?

AIM:To investigate the effects of Helicobacter pylori (H pylori)eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer. METHODS:A multicenter prospective cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture,Japan.The study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication(eradication group)or conventional antacid therapy(non-eradication group).Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and questionnaire surveys,as well as Yamagata Prefectural Cancer Registry data,and was compared between the two groups and by results of H pylori therapy.RESULTS:A total of 4133 patients aged between 13 and 91 years(mean 52.9 years)were registered,and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 years.The sex-and age-adjusted incidence ratio of gastric cancer in the eradication group, as compared with the non-eradication group,was 0.58 (95%CI:0.28-1.19)and ratios by follow-up period(<1 year,1-3 years,>3 years)were 1.16(0.27-5.00),0.50 (0.17-1.49),and 0.34(0.09-1.28),respectively.Longer follow-up tended to be associated with better prevention of gastric cancer,although not to a significant extent.No significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy(32/2451 patients,1.31%)and those with treatment failure(11/639 patients,1.72%).Among patients with duodenal ulcer,which is known to be more prevalent in younger individuals,the incidence of gastric cancer was significantly less in those with successful eradication therapy(2/845 patients,0.24%)than in those with treatment failure(3/216 patients,1.39%). CONCLUSION:H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer.

Early aggressive therapy for severe extensive ulcerative colitis

The current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using in· iximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with in· iximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.

Effects of killing Helicobacter pylori quadruple therapy on peptic ulcer: A randomized double-blind clinical trial

AIM: To study the therapeutic efficacy of a Chinese and Western integrated regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated peptic ulcers(PU).METHODS: With prospective and double-blind controlled method, seventy-five active PU patients with H pylori infection were randomized to receive one of the following three regimens: (1) new triple therapy (group A:lansoprazole 30 mg qd, plus clarithromycin 250 mg bid,plus amoxycillin 500 mg tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3)placebo(group C: gastropine 3 tablets bid for 4 wk).H pylori eradication and ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The patients were followed up for 5 years.RESULTS: Both the healing rate of PU and H pylori eradication rate in group B were significantly higher than those in group C (100% and 96.4% vs 20% and 0%,respectively, P＜0.005), but there was no significant difference compared to those in group A (88% and92%, P＞0.05). The healing quality of ulcer in group B was superior to that in groups C and A (P＜0.05). The recurrence rate of PU in group B (4%) was lower than that in group A (10%) and group C (100%, P＜0.01).CONCLUSION: Killing Helicobacter pylori quadruple therapy can not only promote the eradication of H pylori and healing quality of ulcer but also reduce recurrence rate of ulcer.

Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy

AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.

Biological therapy for ulcerative colitis:An update

Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-αagents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab,oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM:To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease(CD)and ulcerative colitis(UC).METHODS:The data from 41 patients with CD and 22 patients with UC were assessed.Twenty-four CD patients received infliximab,and 17 received adalimumab.The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.RESULTS:Mucosal healing was achieved in 23 CD and7 UC patients.Biological therapy had to be restarted in78%of patients achieving complete mucosal healing with CD and in 100%of patients with UC.Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.CONCLUSION:Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.

Observation of the Effect of Triple Therapy on Duodenal Ulcer with HP Posity

Thirty-foar cases of duodenal ulcer with Hp osity weve treated with Ompeperazole, Amoxi-cillin and Tindazole, which were compared with 34 cases of Hp positive duodenal ulcer treated with omeperazole only. The duration of treatment were both one week and all the patients were re-examed at one month after treatment. The result showed that the huring rate of ulcers (HRU) in triple therapy group was 88. 2%, uhile that of the contr group was 82. 3%. No significant difference was observed in the two groups (p>0.05). Hp eradication rate (HER) in triple therapy group was 91. 7%, while that of the control group was 41. 1 %. There was significant difference between the HERs of the two gronps (p<0.01 ). In the 45 cases with Hp eradication, ulcers in 44 cases hared, with huring rate of 97. 8%. In the 23cases without Hp eradication, ulcers in 14 cases hured, with huring rate of 60. 9%. There was significant difference between these two gronps (p<0.05), which suggested the significant improvement of HRU of-ter Hp eradication. The triple therapy has the advantages such as high HRU, high rate of tolerance and no severe side effects. The therapy deserve recomrnendation clinically.

Diabetic foot ulcer:A comprehensive review of pathophysiology and management modalities

Diabetic foot ulcer (DFU) is a debilitating and severe manifestation ofuncontrolled and prolonged diabetes that presents as ulceration, usually locatedon the plantar aspect of the foot. Approximately 15% of individuals with diabeteswill eventually develop DFU, and 14%-24% of them will require amputation ofthe ulcerated foot due to bone infection or other ulcer-related complications. Thepathologic mechanisms underlying DFU are comprise a triad: Neuropathy,vascular insufficiency, and secondary infection due to trauma of the foot.Standard local and invasive care along with novel approaches like stem celltherapy pave the way to reduce morbidity, decrease amputations, and preventmortality from DFU. In this manuscript, we review the current literature withfocus on the pathophysiology, preventive options, and definitive management ofDFU.

Emerging role of dual biologic therapy for the treatment of inflammatory bowel disease

Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well established guidelines and recommendations for both single agent biologic treatments,and with combination therapy of a biologic agent with a small molecule agent in maintenance therapy.In recent times,there has been increasing interest and experience using dual biologic therapy(DBT)in IBD,primarily in difficult to treat and refractory cases with high disease burden.However,published data on use,experience and safety profiles is limited and large-scale studies remain low in number in this developing area.We therefore aim to present a summary and review of the available published data in this area to help us better understand the emerging role of DBT in IBD.

Effect of Carbon Dioxide Therapy on Diabetic Foot Ulcer

Ulceration of diabetic foot represents one of the most concerning complications associated with uncontrolled blood sugar in diabetes mellitus. The aim of this study is to evaluate the condition of twenty-two diabetic patients with different degrees of ulceration in their feet after daily secessions of carbon dioxide therapy. Blood flow to the affected foot was measured by Doppler;also the size, color, degree of ulceration and sensation of the ulcerative area were all evaluated. Results showed improvement of blood flow to the affected foot as well as improvement in the sensation and color of the ulcerative area. It was concluded that carbon dioxide therapy of diabetic foot was promising and needed thorough investigation to be brought widely into application.