RESUMO
Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.
Assuntos
Doença de Crohn , Ustekinumab , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Masculino , Feminino , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Estudos Prospectivos , Seguimentos , Indução de Remissão , HungriaRESUMO
INTRODUCTION: Post-COVID syndrome may affect the gastrointestinal tract. However, risk factors of post-COVID syndrome are still unknown. OBJECTIVE: We aimed to identify the most common gastrointestinal symptoms, abnormal laboratory findings and risk factors relevant to post-COVID syndrome. METHOD: In this retrospective study, we included 79 patients admitted to Semmelweis University Department of Surgery, Transplantation and Gastroenterology between October 2020 and September 2022. We investigated clinical data, laboratory findings and determined the major risk factors. RESULTS: Most of the patients were women (46/79), their mean age was 47.6 years and patients were overweight (BMI: 26.3 kg/m2). The most common comorbidities were cardiovascular diseases (21/79), hypertension (20/79), diabetes (11/79) and malignant diseases (9/79). Typical indications for gastroscopy were dyspepsia (16/79) and epigastric pain (10/79). The most common indications for colonoscopy were diarrhea (29/79) and weight loss (28/79). Among abnormal laboratory findings, liver enzymes levels (GOT: 83.5 U/L, GPT: 85 U/L, GGT: 70 U/L) and ferritin (351.5 ng/mL) were higher in post-COVID patients. Typical conditions diagnosed by gastroscopy, colonoscopy and abdominal ultrasound were gastroesophageal reflux disease (11/26), irritable bowel syndrome (2/19) and diffuse hepatic lesions, respectively. The number of unvaccinated patients was higher compared to those receiving any COVID-19 vaccines (58% vs. 29%). Of the vaccinated patients, 12 patients received mRNA vaccines (10 Pfizer-BioNTech, 2 Moderna) and 6 patients received viral vector vaccines (2 AstraZeneca, 4 Sputnik V). CONCLUSION: We identified female gender, obesity, cardiovascular diseases, cancer, hypertension and diabetes as major risk factors of post-COVID syndrome. Vaccinated status may prevent post-COVID gastrointestinal symptoms. Orv Hetil. 2023; 164(31): 1206-1212.
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COVID-19 , Doenças Cardiovasculares , Hipertensão , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Vacinas contra COVID-19 , Estudos Retrospectivos , COVID-19/complicaçõesRESUMO
BACKGROUND, AIMS: Patients with inflammatory bowel disease (IBD) have a more than twofold higher risk of venous thromboembolic events (VTE) than the general population. The etiology is complex, and the role of medication is not precisely defined.We aimed to assess the effect of anti-tumor necrosis factor alpha (anti-TNFα) drugs and conventional anti-inflammatory therapy, namely corticosteroids (CS), immunomodulators (IM), and 5-aminosalicylates (5-ASA) on VTE in IBD. METHODS: A systematic search was performed in five databases on the 22nd of November 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios (OR) with 95% confidence intervals (CI), using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS: The quantitative analysis included 16 observational studies, with data from 91,322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE (proportion: 0.05, CI: 0.02-0.10), than patients treated with CS (proportion: 0.16, CI: 0.07-0.32), with OR=0.42 (CI: 0.25-0.71). IMs resulted in similar proportions of VTE compared with biologics (0.05, CI: 0.03-0.10), with OR=0.94 (CI: 0.67-1.33). The proportion of patients receiving 5-ASA having VTE was 0.09 (CI: 0.04-0.20), with OR=1.00 (CI: 0.61-1.62). CONCLUSIONS: Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.
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Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.
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COVID-19 , Humanos , Alanina Transaminase , Estudos Retrospectivos , Aspartato Aminotransferases , PrognósticoRESUMO
Retroperitoneal fibrosis is the chronic, nonspecific inflammation of the retroperitoneum. About 75% of the cases are idiopathic. The pathomechanism of the disorder is not clearly defined. Autoimmune inflammation and secondary fibrosis are the main suspected mechanisms against an unknown factor possibly related to atherosclerosis. Symptoms and laboratory parameters are nonspecific which make the diagnosis difficult. At the time of the diagnosis complications are often present. After the urological and surgical management of the complications, the aim of the medical treatment is immunosuppression. Corticosteroids are usually used for treatment, although the optimal dosage and the duration of the treatment are not known. After therapy cessation relapse may occur, requiring repeated steroid therapy or addition of steroid sparing drugs. Predicting factors for treatment response, corticosteroid demand or relapse are not known. Authors review the medical history of two patients with retroperitoneal fibrosis and discuss diagnostic difficulties of this disorder.
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Fibrose Retroperitoneal , Corticosteroides/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva , Fibrose Retroperitoneal/complicações , Fibrose Retroperitoneal/diagnóstico , Fibrose Retroperitoneal/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
Over the past decade, the application of anticoagulant and antiplatelet agents for various cardiovascular and hematologic conditions has become more widespread. These medications can decrease the risk of thromboembolic events, meanwhile may potentiate gastrointestinal bleeding. The decision to reverse anticoagulation, thereby risking thromboembolic complications, must be carefully weighted against the increased risk of bleeding when maintaining anticoagulation. Elective procedures should be delayed in patients on temporary anticoagulation therapy (e.g. those with deep vein thrombosis). For procedures considered to have a low risk of bleeding (e.g. diagnostic endoscopy and biopsy) there is no need to discontinue or adjust anticoagulation. For procedures with a higher risk of bleeding (e.g. polypectomy and biliary sphincterotomy), an individual approach is required. This approach might include stopping oral anticoagulant therapy with or without the administration of unfractionated heparin or low-molecular-weight heparin for the pre-procedure and post-procedure periods, during which the patient's international normalized ratio is in the subtherapeutic range. Antiplatelet drugs (aspirin, clopidogrel, ticlopidine) may also increase the risk of bleeding induced by gastrointestinal endoscopic procedures. There is no indication to stop the therapy before esophagogastroduodenoscopy. Discontinuation of aspirin 4-7 days (according to the cardiovascular risk) before other endoscopic procedures is recommended. When aspirin is indicated for primary prevention, it can be resumed 14 days and 10 days after polypectomy and sphincterotomy, respectively. In cases of secondary prevention, it should be resumed after 1 week.
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Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Tromboembolia/prevenção & controle , Algoritmos , Ampola Hepatopancreática/cirurgia , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Árvores de Decisões , Esquema de Medicação , Hemorragia Gastrointestinal/induzido quimicamente , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Coeficiente Internacional Normatizado , Pólipos Intestinais/cirurgia , Prevenção Primária , Prevenção SecundáriaRESUMO
Whipple's disease is a rare multisystemic infectious disease of bacterial origin characterized by variable clinical manifestations, and an insidious and chronic relapsing course. Untreated disease can be even fatal. The presence of the characteristic (though not specific) triad of weight loss, chronic diarrhea and arthralgias may raise its suspicion. When chronic intermittent fever and lymphadenopathy are associated, the suspicion is substantial. Recognition of the causative agent, Tropheryma whippelii with unique characteristics was essential. Despite the presumed ubiquitous presence of the bacteria the disease probably occurs only in cases of immunological host susceptibility. Presence of the bacteria living and multiplying especially in macrophages has suggested alterations of the mononuclear-phagocytic system. (Whipple's disease is commonly mentioned as a macrophage disorder.) Clinical manifestations are quite diverse. While it has traditionally been regarded as a gastrointestinal disease, currently is considered to be a systemic disorder. In cases of suspected infection the approach of first choice is upper gastrointestinal endoscopy. Small, whitish-yellow diffusely distributed plaques alternating with an erythematous, erosive, friable mucosa in the postbulbar region of the duodenum or in the jejunum can appear. Histological samples indicate tissue infiltration of macrophages with intracellular bacterial invasion. The hallmark of Whipple's disease is the presence of PAS positive macrophages in the lamina propria of duodenal biopsy specimens, still the diagnosis needs to be confirmed with the detection of bacteria by PCR. The selection of antibiotics and duration of treatment still remains largely empiric.
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Doença de Whipple , Diagnóstico Diferencial , Humanos , Prognóstico , Doença de Whipple/diagnóstico , Doença de Whipple/epidemiologia , Doença de Whipple/etiologia , Doença de Whipple/fisiopatologia , Doença de Whipple/terapiaRESUMO
Metabolic syndrome (MetS), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor (IGF1R) signaling pathway. The IGF1R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1R-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from MetS who are at increased risk of colorectal cancer. However, therapeutic responses to targeted therapies are often shortlived, since a signaling crosstalk of IGF1R with other receptor tyrosine kinases or autophagy exists, leading to acquired cellular resistance to therapy. From a pharmacological point of view, it is attractive to speculate that synergistic beneï¬ts could be achieved by inhibition of one of the key effectors of the IGF1R pathway, in parallel with the pharmacological stimulation of the autophagy machinery, but cautiousness is also required, because pharmacologic IGF1R modulation can initiate additional, sometimes unfavorable biologic effects.
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Autofagia , Colite/metabolismo , Neoplasias Colorretais/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptores de Somatomedina/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Colite/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/etiologia , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Receptor IGF Tipo 1 , Receptores de Somatomedina/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
This pilot study was devoted to the effect of static magnetic field (SMF)-exposure on erosive gastritis. The randomized, self- and placebo-controlled, double-blind, pilot study included 16 patients of the 2nd Department of Internal Medicine, Semmelweis University diagnosed with erosive gastritis. The instrumental analysis followed a qualitative (pre-intervention) assessment of the symptoms by the patient: lower heartburn (in the ventricle), upper heartburn (in the oesophagus), epigastric pain, regurgitation, bloating and dry cough. Medical diagnosis included a double-line upper panendoscopy followed by 30 min local inhomogeneous SMF-exposure intervention at the lower sternal region over the stomach with peak-to-peak magnetic induction of 3 mT and 30 mT m(-1) gradient at the target site. A qualitative (post-intervention) assessment of the same symptoms closed the examination. Sham- or SMF-exposure was used in a double-blind manner. The authors succeeded in justifying the clinically and statistically significant beneficial effect of the SMF- over sham-exposure on the symptoms of erosive gastritis, the average effect of inhibition was 56% by p = 0.001, n = 42 + 96. This pilot study was aimed to encourage gastroenterologists to test local, inhomogeneous SMF-exposure on erosive gastritis patients, so this intervention may become an evidence-based alternative or complementary method in the clinical use especially in cases when conventional therapy options are contraindicated.
Assuntos
Gastrite/terapia , Magnetoterapia/métodos , Campos Magnéticos , Adulto , Idoso , Método Duplo-Cego , Feminino , Gastrite/diagnóstico , Azia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
The etiology and pathogenesis of collagenous colitis (CC) is poorly understood and probably multifactorial; many potential pathophysiological mechanisms have been described, although none have been conclusively proved. Circumstantial evidence suggests that CC appears as an autoimmune response to a luminal or epithelial antigen of unknown origin. Infections and certain drugs (e.g. NSAID, lansoprazole) may act as triggers for an immune-mediated process. CC is characterized clinically by chronic watery, nonbloody diarrhea with normal endoscopic appearance and without radiological abnormalities, but specific microscopic changes in the colon. Histopathology is featured by the presence of a thickened subepithelial collagen band adjacent to the basal membrane. Up to 40% of patients with CC have associated diseases of autoimmune or inflammatory origin, such as thyroid disease, coeliac disease, rheumatoid arthritis, diabetes mellitus, Sjögren's syndrome, CREST syndrome, scleroderma, pernicious anemia, and sarcoidosis. Prurigo nodularis is a chronic condition characterized by intensely pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It is assumed to represent a cutaneous reaction pattern to repeated scrubbing or scratching caused by pruritus. We report a case of CC and prurigo nodularis. To our knowledge, this association has not been reported earlier.