Immunosuppressive therapies for inflammatory bowel disease

Inflammatory bowel disease (IBD) is comprised of Crohn’s disease and ulcerative colitis, both chronic inflammatory intestinal disorders of unknown etiology characterized by a waxing and waning clinical course. For many years, the drug therapy was limited to sulfasalazine and related aminosalicylates, corticosteroids and antibiotics. Studies suggesting that the pathophysiology of these disorders relates to a disregulated, over-active immune response to indigenous bacteria have led to the increasing importance of immunosuppressive drugs for the therapy of IBD. This review details the mechanisms of action, clinical efficacy, and adverse effects of these agents.

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk(± 5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments(antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections(type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year(± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance(MR) score ≥ MR1.RESULTS:Twenty-nine patients(55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76(range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29(13.7%) developed clinical recurrence,6/29(20.7%) endoscopic recurrence and 7/19(36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance was found between clinical-endoscopic recurrence(k = 0.76,P < 0.001) and clinical-morphological recurrence(k = 0.63,P = 0.003).Correlation between endoscopic and radiological findings was good(comparing the 5-point Rutgeerts score with the 4-point MR score,a score of i4 was classified as MR3,i3 as MR2,and i2-i1 as MR1)(P < 0.001,r s = 0.825).During follow-up,five(17.2%) patients needed adalimumab dose intensification(40 mg/wk);Mean time to intensification after the introduction of adalimumab treatment was 8 mo(range:5 to 11 mo).In three cases(10.3%),a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk.One patient suffered an adverse event.CONCLUSION:Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

脑血管病患者血清肿瘤坏死因子变化的研究

观察１１１例脑血管病患者血清ＴＮＦ水平的变化。结果表明：脑血管病患者血清ＴＮＦ水平较正常对照组显著升高（Ｐ＜０．００１），且急性期患者血清ＴＮＦ水平亦较恢复期患者显著升高（Ｐ＜０．００１），表明测定脑血管病患者血清ＴＮＦ有助于临床上观察病情发展、治疗效果及对预后的判断。

Longest survival with primary intracranial malignant melanoma:A case report and literature review

BACKGROUND Primary intracranial malignant melanoma(PIMM)is rare,and its prognosis is very poor.It is not clear what systematic treatment strategy can achieve long-term survival.This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature.CASE SUMMARY The patient is a 47-year-old Chinese man who suffered from dizziness and gait disturbance.He underwent surgery for right cerebellum melanoma and was subsequently diagnosed by pathology in June 2000.After the surgery,the patient received three cycles of chemotherapy but relapsed locally within 4 mo.Following the second surgery for total tumor resection,the patient received an injection of Newcastle disease virus-modified tumor vaccine,interferon,andβ-elemene treatment.The patient was tumor-free with a normal life for 21 years before the onset of the recurrence of melanoma without any symptoms in July 2021.A third gross-total resection with adjuvant radiotherapy and temozolomide therapy was performed.Brain magnetic resonance imaging showed no residual tumor or recurrence 3 mo after the 3rd operation,and the patient recovered well without neurological dysfunction until the last follow-up in June 2022,which was 22 years following the initial treatment.CONCLUSION It is important for patients with PIMM to receive comprehensive treatment to enable the application of the most appropriate treatment strategies.Long-term survival is not impossible in patients with these malignancies.

Silencing the gene encoding C/EBP homologous protein lessens acute brain injury following ischemia/reperfusion

C/EBP homologous protein, an important transcription factor during endoplasmic reticulum stress, participates in cell apoptosis mediated by endoplasmic reticulum stress. Previous studies have shown that C/EBP homologous protein mediates nerve injury during Alzheimer＇s disease, subarachnoid hemorrhage and spinal cord trauma. In this study, we introduced C/EBP homologous protein short hairpin RNA into the brains of ischemia/reperfusion rat models via injection of lentiviral vector through the left lateral ventricle. Silencing C/EBP homologous protein gene expression significantly reduced cerebral infarction volume, decreased water content and tumor necrosis factor-α and interleukin-1β mRNA expression in brain tissues following infarction, diminished the number of TUNEL-positive cells in the infarct region, decreased caspase-3 protein content and increased Bcl-2 protein content. These results suggest that silencing C/EBP homologous protein lessens cell apoptosis and inflammatory reactions, thereby protecting nerves.