Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.     

Reduced healthcare utilization following successful hepatitis C virus treatment in HIV‐co‐infected patients with mild liver disease

New direct‐acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult‐to‐treat, including those HIV/HCV co‐infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co‐infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV‐co‐infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty‐three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5000 per‐patient) compared to (£10 775 per‐patient) non‐SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co‐infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.     

Medical treatment: does it influence the natural course of inflammatory bowel disease?

It is difficult to predict the clinical course of inflammatory bowel disease (IBD). Moderately sick Crohn's disease (CD) patients and patients with distal ulcerative colitis (UC) may get better even without medical or surgical treatment. Once better, they may continue in remission even without treatment. If they are not treated, there are several factors that predict whether they will maintain remission. Most patients will probably alternate between remission and relapse, with 10% having a relapse-free course after 10 years, and only 1% having a continuously active course. Frequent relapses initially are associated with active disease later on, but the disease activity course is independent of the response to the initial medical treatment. There is a cumulative frequency of operation of 50-80% and of reoperation of 33% in CD, which suggests that CD has a more serious course than UC. In UC, the overall probability of surgery is 33% for pancolitis and 10% for proctitis within 5 years of diagnosis, and the majority of patients are operated on within the first few years. Maintenance treatment with sulphasalazine (SASP) and 5-aminosalicylic acid (5-ASA) in UC has reduced relapse rates to about half over a 1-year follow-up period. The use of 5-ASA for maintenance of CD has been shown to result in only a modest therapeutic gain, while azathioprine and 6-mercaptopurine (6-MP) improve the relapse frequency for at least 3 years whilst on treatment. Changes in disease distribution in UC are part of the natural course of the disease, which should have implications for medical treatment strategies, and affects the risk of colectomy and colonic cancer. Certain enviromental factors are thought to determine disease activity and disease outcome in UC and CD. Patient compliance with prescribed medication and clinical check-ups must be considered another non-specific variable affecting the clinical outcome. IBD frequently requires potent medication with side effects that limit patients' acceptance. Such patients often resort to medicinal herbs, acupuncture, and homeopathy, which may alter the expected course.     

Treatment of spondyloarthropathy with 5-aminosalicylic acid (mesalazine): an open trial

OBJECTIVE: Ankylosing spondylitis (AS) and spondyloarthropathy (SpA) are inflammatory diseases of unknown etiology. Various exogenous and endogenous (inherited) factors play a role in their development. Sulfasalazine (SSZ) is generally accepted as a disease modifying drug in the treatment of AS and SpA. Which part of SSZ, 5-acetylsalicylic acid (5-ASA, mesalazine) or sulfapyridine (SP), is the effective moiety is unknown. As the bowel, colon, and the ileum play an important role in the development of AS and SpA, it may be possible that 5-ASA is the effective moiety, with a similar mode of action as in the treatment of inflammatory bowel disease. To determine the efficacy of 5-ASA an open pilot study was done in 2 groups of patients with SpA. METHODS: Twenty patients with SpA, who were taking SSZ, were switched to 5-ASA (Pentasa), and 19 patients with active SpA were treated with 5-ASA without previous administration of SSZ. RESULTS: In the first group, 17 (85%) patients responded with respect to the physician global clinical assessment compared to the previous SSZ treatment period; whereas in the second patient group a statistically significant improvement was obtained in erythrocyte sedimentation rate. CONCLUSION: The results support our hypothesis that 5-ASA might be the active moiety of SSZ in the treatment of SpA.     

Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort

BACKGROUND AND AIMS: Mucosal healing (MH) in inflammatory bowel disease may be an important sign of efficacy of treatment and a prognostic marker of long-term disease. The aim of the study was to examine both the possible predictors of mucosal healing and the impact of healing on subsequent course of disease. METHODS: In 740 incident patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 1990 and 1994 (before biologic therapy was available), demographics and symptoms were recorded. Clinical and endoscopic evaluations were done at baseline before treatment and repeated after 1 and 5 years in 495 patients. RESULTS: In UC patients, education longer than 12 years and extensive disease at diagnosis were significant predictors of MH after 1 year (adjusted P = .004 and P = .02, respectively). MH was significantly associated with a low risk of future colectomy (P = .02). In patients with CD, fever at diagnosis and medical treatment without steroids were significant predictors for MH (adjusted P = .03 and P = .01, respectively). MH was significantly associated with less inflammation after 5 years (P = .02), decreased future steroid treatment (P = .02). CONCLUSIONS: Several factors predicted subsequent MH. Education as predictor may implicate the importance of coping, compliance, or lifestyle. MH after 1 year of treatment is predictive of reduced subsequent disease activity and decreased need for active treatment. The present results give further strength to the use of mucosal healing as a clinical indicator and treatment goal in inflammatory bowel disease.     

The cost-effectiveness of long-term antiviral therapy in the management of HBeAg-positive and HBeAg-negative chronic hepatitis B in Singapore

The purpose of this study was the economic evaluation of short-duration treatments of chronic hepatitis B (CHB) and longer duration antiviral treatment for up to 5 years. Two 10-health state Markov models were developed for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients respectively. The perspective of this economic evaluation was the Singapore healthcare system and CHB patient. The models followed cohorts of HBeAg-positive and HBeAg-negative CHB patients, respectively, over a period of 40 years, by which time the majority of the cohorts would have died if left untreated. Costs and benefits were discounted at 5% per annum. Annual rates of disease progression and the magnitude of treatment effects were obtained from the literature, with a focus on data obtained in Asian patients and meeting the criteria for therapy as described in internationally recognized management guidelines. Short-course therapy with alpha-interferon, or 1-year treatment with pegylated interferon alpha-2a, lamivudine or adefovir had limited impact on disease progression. In contrast, treatment of CHB with antiviral therapy for 5 years substantially decreased the rate of disease progression. Treatment with lamivudine for 1-year is highly cost-effective compared with no treatment of CHB but has limited effect on reducing the rate of disease progression. Compared with 1-year treatment with lamivudine, sequential antiviral therapies for up to 5 years (i.e. lamivudine plus adefovir on emergence of lamivudine resistance or adefovir plus lamivudine on emergence of adefovir resistance) are highly cost-effective by international standards. These conclusions are robust to uncertainties in model inputs and are consistent with the findings of other recently published studies.     

A case of Crohn's disease successfully treated with infliximab without steroid]

A 39-year-old man diagnosed as Crohn's disease suffered steroid induced psycosis during treatment for Crohn's disease on July 2001. He was admitted on May 2002, because of progressing high fever, abdominal pain and diarrhea. He was treated with infriximab (5mg/kg) together with mesalazine without steroid. The treatment induced rapid improvement of systematic symptoms together with laboratory data and colonoscopic findings. He kept remission for more than 10 months after a single administration of infliximab (5mg/kg). The case is suggestive of wider indication of infliximab for Crohn' s disease.     

Infective endocarditis: analysis of 300 episodes]

PURPOSE: Study of clinical features and etiologic agents, treatment and mortality of patients with infective endocarditis (IE). PATIENTS AND METHODS: 300 episodes of IE occurring in 288 patients, ages ranged between 0.2 and 78 (mean 30.76) years; 185 (62%) episodes occurred in males. RESULTS: a) etiologic agents: viridans group streptococci in 93 (31%) episodes, enterococci en 21 (7%), group D-non enterococci in 19 (6%) (13 S. bovis), other streptococci in 14 (5%), Staphylococcus aureus in 59 (20%), Staphylococcus epidermidis in 14 (5%), gram-negative bacteria in 16 (5%), gram-positive bacteria other than streptococci and staphylococci and staphylococci in 8 (3%), fungi in 4 (1%). The etiologic agents were not identified in 52 (17%) episodes; b) underlying cardiac diseases: valvular heart disease in 119 (40%) episodes, congenital heart disease in 37 (12%), prosthetic heart valves in 69 (23%), other heart diseases in 6 (2%). There was no evidence of previous heart disease in 69 (23%); c) treatment: surgical treatment was undertaken in 102 (34%) episodes. The frequency of surgical treatment in relation to the etiologic agents ranged between 1% (non-group D streptococcus) and 62% (negative blood cultures). The frequency of operation in relation to underlying heart disease ranged between 17% (other heart diseases), 19% (congenital heart disease) and 54% (prosthetic heart valve); d) mortality: 78 (26%) patients died, 56 (28%) of the 198 submitted to medical treatment and 22 (21%) of the 102 submitted also to surgical treatment. The mortality in the different groups of etiologic agents ranged between 5% (non group D streptococcus) and 62% (gram-positive bacteria other than streptococci ans staphylococci); in relation to the underlying with other heart disease, 19% in valvular heart disease patients, 21% in patients with congenital heart disease, 23% in patients without known heart disease and 43% in patients with prosthetic heart valves. CONCLUSION: The mortality associated with IE remains still high in spite of modern treatment; the mortality is different in relation to the cardiac status before the IE.     

Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration

OBJECTIVE: To use individual patient data from rheumatoid arthritis (RA) clinical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvement (the "ACR response"). METHODS: Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of which 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 induction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. RESULTS: A total of 1,435 patients (549 in placebo-controlled trials, 886 in comparative trials) were studied. In both active treatment and placebo groups, disease duration had a strong effect on the likelihood of patient response (e.g., with any active treatment, the response rate was 53% for patients with < or =1 year of disease, 43% for 1-2 years' disease duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for > 10 years; P = 0.001). Decreasing response with greater disease duration was seen during treatment with most of the individual active drugs, as well as with placebo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher disease functional class (according to the Steinbrocker criteria), low disease activity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with long-standing disease. The difference between active treatment and placebo response rates was not affected by disease duration nor by other factors associated with the ACR response. CONCLUSION: RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, prior DMARD use, disease functional class, and disease activity also have effects on the likelihood of patient response to treatment. This has implications for trial interpretation and for the clinical expectations of RA patients.     

Trends in endocrine therapy and chemotherapy for early breast cancer: a focus on the premenopausal patient

Purpose: The majority of breast cancers are diagnosed at an early stage, and treatment is focused on cure and prolonging disease-free survival. Local therapy (surgery and/or radiation treatment) is standard, along with systemic adjuvant therapy that may effectively prevent or delay relapse and death in early-stage disease. In premenopausal women, adjuvant therapeutic approaches include combination cytotoxic chemotherapy and endocrine therapy. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was the established chemotherapy regimen; however, newer regimens have more recently been introduced that may offer some benefit over CMF including anthracycline-containing regimens [e.g. cyclophosphamide, epirubicin and 5-fluorouracil (CEF)], and taxane-containing regimens. For women with oestrogen receptor (ER)-positive disease, a second option is endocrine therapy that aims to suppress mitogenic oestrogen signalling. Until recently, 5 years of tamoxifen was regarded as the standard adjuvant endocrine treatment in ER-positive disease. Ovarian ablation is also effective in premenopausal women, and can be achieved by surgery, radiotherapy, or via the use of a luteinising hormone-releasing hormone analogue such as goserelin. Combining tamoxifen and goserelin treatment provides more effective oestrogen blockade than either drug alone. However, as the third-generation aromatase inhibitors (AIs) have demonstrated improved efficacy over tamoxifen in postmenopausal women with early and advanced disease, combination treatment with goserelin plus an AI may provide optimal oestrogen blockade in premenopausal patients. Conclusions: This review assesses the relative merits of chemotherapeutic and endocrine approaches for the treatment of early breast cancer, and summarises relevant ongoing clinical trials, with an emphasis on the premenopausal setting.     

Oral mesalazine for the treatment of Crohn's disease: clinical efficacy with respect to pharmacokinetic properties

The release of 5-ASA from various preparations depends on the presence of bacterial azoreductases (sulphasalazine, olsalazine, balsalazide) or the pharmacokinetic properties of the mesalazine-containing pharmaceutical preparations. The differences of the 5-ASA release from the various preparations account for the different anatomic sites of actions. In this regard, a close relationship between the regional intraluminal concentrations of 5-ASA and the clinical response can be assumed. The aim of the present paper is to survey clinical trials in Crohn's disease with special respect to the pharmacokinetic properties of the used mesalazine containing preparations. There are clear differences between the different coated 5-ASA formulas in respect to 5-ASA release and in respect to their pharmacokinetic properties leading to a different therapeutic efficacy in Crohn's disease. The detailed analysis indicates that higher doses of 5-ASA (> 3 g/d) are required for the acute phase treatment. 4.5 g Eudragit-L-coated 5-ASA tablets are almost equally as potent as glucocorticosteroids for the treatment of active Crohn's disease. Clinical efficacy has been demonstrated for Eudragit-L-coated tablets even at a low dose of 1-1.5 g 5-ASA/day in the maintenance treatment of remission of Crohn's disease. This has also been shown for Eudragit-S-coated tablets at a dose of 2.4 g 5-ASA/day, while even 3 g 5-ASA of an Eudragit-L/S formula as well as the ethylcellulose-coated formulas up to 4 g 5-ASA/day were ineffective, except for a high risk group. On the basis of the published trials, there is clear evidence that post-operative prophylaxis with 5-ASA requires daily doses higher than 1.5 g. Ethylcellulose-coated 5-ASA has only been effective in Crohn's disease limited to the small bowel and should not be given to patients with ileo-colonic or colonic disease. Moreover, Eudragit-L-coated 5-ASA preparations have shown to be effective in both ileal and colonic disease concerning their clinical efficacy in post-operative prophylaxis. In contrast, endoscopic efficacy has been demonstrated for ethylcellulose as well as Eudragit-S-coated formulas. Treatment of Crohn's disease with orally administered 5-ASA can generally be regarded as an effective and well-tolerated therapy. However, the distinct therapeutic goal (acute phase treatment, maintenance therapy or post-operative prophylaxis), the involved areas of the gut and the specific release of the drug administered have to be considered.     

Non-small cell lung cancer with chest wall invasion: evolution of surgical treatment and prognosis in the last 3 decades

STUDY OBJECTIVES: The treatment of patients with non-small cell lung cancer (NSCLC) that is invading the chest wall is still debated. We aim to illustrate the improvements in treatment results that have occurred over last decade. DESIGN: Retrospective analysis of our experience and an overview of the literature. SETTING: Department of Surgery, San Giuseppe Hospital, University of Milan. PATIENTS: From January 1970 to December 1999, of 2,738 patients with NSCLC, we operated on 146 patients (5.4%) with chest wall invasion by NSCLC. Superior sulcus tumors and tumors invading the diaphragm or mediastinum were excluded. We reclassified all cases according to the current TNM classification. RESULTS: We registered one postoperative death (0.69%) and five major complications (3.4%). From 1970 to 1979, of 32 patients, 10 underwent an exploratory thoracotomy (ET) and 22 underwent a radical resection (stage IIB disease, 17 patients; stage IIIA disease, 5 patients). The 5-year survival rate was 22.7% (25% for stage IIB disease). From 1980 to 1989, of 67 patients, 11 underwent an ET and 56 underwent a radical resection (stage IIB disease, 34 patients; stage IIIA disease, 12 patients; stage IIIB disease, 5 patients; and stage IV disease, 5 patients). The survival rate following radical resection was 14.1%, ranging between 23.5% for patients with stage IIB disease and 0% (3 years, 14%) for those with stage IIIA disease. From 1990 to 1999, of 47 patients, 2 underwent an ET, 2 underwent an exploratory thoracoscopy, and 43 underwent a radical resection (stage IIB disease, 23 patients; stage IIIA disease, 20 patients). The survival rate was 42.7% (stage IIB disease, 78.5%; stage IIIA disease, 7.2%). CONCLUSIONS: Considering the low morbidity, mortality, and significant improvement in survival during the last decade, we advocate the performance of radical en bloc resection for the treatment of chest wall invasive NSCLC.     

Optimizing anti-TNF treatment in inflammatory bowel disease

Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor necrosis factor (TNF) has changed our therapy of Crohn's disease. Infliximab is indicated in refractory luminal and fistulizing Crohn's disease. In patients with luminal disease, a single intravenous (i.v.) dose of 5 mg/kg is efficacious; in fistulizing disease, an i.v. loading therapy of 5 mg/kg at weeks 0, 2, and 6 is advocated. Because the majority of patients will relapse if not re-treated, a long-term strategy is necessary. The optimal long-term approach is systematic re-treatment with 5 mg/kg every 8 weeks. Episodic therapy on relapse also is possible but is less efficacious and frequently is associated with problems resulting from the formation of antibodies to infliximab (ATI). If treatment is episodic, maintenance therapy with immunosuppression (azathioprine [AZA]/6-mercaptopurine [6-MP] or methotrexate) is mandatory. Trial data suggest that systematic maintenance with 8 weekly doses of infliximab decreases the rate of complications, hospitalizations, and surgeries. These effects probably are achieved thanks to thorough healing of the bowel. Infliximab also is indicated in treating corticosteroid-dependent Crohn's disease and extraintestinal manifestations of Crohn's disease. There are no data yet that support its use as first-line therapy. The data in ulcerative colitis (UC) are conflicting and we should await the results of 2 large controlled trials (ACT1 and ACT2) to position infliximab in the treatment of UC. Other anti-TNF strategies have been less effective than infliximab in the treatment of IBD until now. The results with thalidomide are promising but much more research into small molecules inhibiting TNF and other proinflammatory cytokines is necessary. Safety problems with antibody treatment mainly concern immunogenicity leading to infusion reactions, loss of response, and serum sickness-like delayed infusion reactions. The rate of opportunistic infections is increased mainly in patients treated concomitantly with immunosuppression. Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased.     

Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept

BACKGROUND: Antisecretory factor (AF), a 41 kDa cloned and sequenced protein, suppresses intestinal inflammation and hypersecretion in animals. Endogenous AF production can be induced by dietary modifications in several animal species, and this feed has been shown to reduce the incidence of diarrhoeal disease in weaning piglets. The role of AF in intestinal disease in humans is not known. AIMS: To study the effects of hydrothermally processed cereals, optimised for AF induction in animals, added to the diet of patients with longstanding symptoms of inflammatory bowel disease (IBD). PATIENTS: Fifty three patients with IBD (ulcerative colitis and Crohn's disease) were entered into the study, and 50 completed follow up. The experimental group consisted of 16 females (mean age 50 (SEM 5) years) and 10 males (41 (4) years) and the placebo group of 12 women (41 (4) years old) and 12 men (51 (5) years). METHODS: Patients were randomised to receive either hydrothermally processed cereals (active treatment) or the same amount of ordinary cereals (placebo treatment) for four weeks in a double blind study design. Baseline diet and medications remained unchanged. Bowel symptoms, plasma levels of AF, and colonic biopsies were evaluated before and after treatment. RESULTS: The active treatment significantly improved subjective ratings of clinical symptoms and increased plasma AF levels compared with placebo. Plasma lipid levels were unaffected. CONCLUSION: Hydrothermally processed cereals can induce AF production in human IBD. This increase in endogenous AF activity is associated with clinical improvement. Further studies are warranted to clarify the exact role of AF in human intestinal disease.     

Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity.

Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease.     

Short course intravenous benzylpenicillin treatment of adults with meningococcal disease

BACKGROUND: Short-course treatment of meningococcal disease (including meningitis) with 4-5 days of an i.v. beta-lactam is of proven efficacy. Since April 1998, all adult patients with meningococcal disease admitted to Auckland Hospital were prospectively treated with 3 days of i.v. benzylpenicillin. AIMS: To assess the clinical features, laboratory findings, disease complications and outcome of patients with meningococcal disease prospectively treated with 3 days of i.v. benzylpenicillin. METHODS: A retrospective chart review of all adult patients with meningococcal disease admitted to Auckland Hospital from April 1998 to December 2002 was conducted. RESULTS: Ninety patients with definite (n = 72) or -probable (n = 16) meningococcal disease were admitted during the study period. Two were excluded on the basis of treatment duration. The remaining 88 patients received a mean +/- standard deviation duration of treatment of 3.1 +/- 0.5 days (excluding those who died while receiving treatment). Six patients (7%) died, four of whom while on treatment. There were no relapses. CONCLUSION: Three days of i.v. benzylpenicillin for the treatment of adults with meningococcal disease is effective.     

5-Aminosalicylates and renal function in inflammatory bowel disease: a systematic review

Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.     

MDA5抗体阳性皮肌炎合并快速进展性肺间质病变的诊治进展

抗黑色素瘤分化相关基因5(MDA5)抗体阳性的皮肌炎（DM）是炎性肌病的特殊亚型，较易合并快速进展的肺间质病变(RPILD)，死亡率高。遗传和环境因素可能共同参与了该病的致病过程；临床表现、呼吸生理参数、影像学特征及血清学标记物可用来判断RPILD发生风险及评估预后。对于MDA5+DM-RPILD目前尚缺乏基于高质量循证医学证据的治疗策略，主流治疗方法是激素+钙调神经磷酸酶抑制剂+环磷酰胺的“三联疗法”和基于JAK抑制剂的方案，早期诊断、准确分层以及个体化治疗是获得良好预后的关键。     

Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression

OBJECTIVE: To study serum levels of citrullinated protein/peptide antibodies (anti-CP) during up to 5 years' follow up of patients with early rheumatoid arthritis (RA), and to relate serum levels to disease course and to treatments in clinical practice. METHODS: 279 patients with early RA were followed up with clinical investigations, radiographs, and measurement of anti-CP at baseline and after 3 months, 1, 2, 3, and 5 years. RESULTS: 160/279 (57.3%) patients were anti-CP positive at the first visit (mean 5 months after first symptoms). During follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti-CP levels fell significantly during the first year, and this drop correlated with the extent of sulfasalazine treatment but not with other drugs or clinical indices. Anti-CP positive and negative patients had similar disease activities at baseline, but during follow up the anti-CP positive patients had worse clinical disease and greater radiological progression, despite at least equally intensive antirheumatic treatment. CONCLUSIONS: Anti-CP are stable during the first 5 years of RA, suggesting that events before rather than after onset of clinical manifestations of disease determine this phenotype. The presence of anti-CP at diagnosis predicts a less favourable disease course and greater radiological progression despite antirheumatic treatment, but subsequent changes in antibody levels do not reflect changes in disease activity. Taken together, these observations suggest that anti-CP positive RA is a distinct clinical and pathophysiological entity.     

126例急性心肌梗死患者院外救治分析

目的分析比较接受院前救治的急性心肌梗死(AMI)患者不同结局的影响因素及其原因。方法回顾性分析126例2008年10月—2011年10月我站收治的AMI患者的临床特征及治疗效果,将126例患者分为治疗无效组(包括死亡、病情恶化)和治疗有效组(包括病情稳定、症状缓解)进行分析,比较各组中性别组成、年龄结构、基础疾病(3个以上)、有无并发症、发病致救治时间。结果治疗有效组97例(其中病情稳定82例,病情缓解15例),治疗无效组29例(其中死亡5例、病情恶化24例),两组男女比例分别为74/23和22/7(P=0.84),中青年和老年人比例分别为治疗有效组为26/71,治疗无效组为2/27(P=0.04),合并有基础疾病者和无基础疾病者比例分别为25/72和23/6(P<0.01),存在并发症者和无并发症者分别为17/80和24/5(P<0.01),发病致救治的时间分别为(82.3±8.1)min和(172.5±32.6)min(P<0.01)。我站AMI抢救成功率为76.98%。结论高龄、存在基础疾病、早期出现并发症及就诊时间长短是AMI院外急救的成功危险因素,如能控制以上各因素,可提高AMI患者的抢救成功率。