ANCA and anti-glomerular basement membrane double-positive patients: A systematic review of the literature

IntroductionDouble-positive patients (DPP) exhibiting anti-glomerular basement membrane (GBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) belong to an entity that is newly and poorly described, mainly in short series. We aimed to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review.MethodsWe performed a systematic review of English-, German-, Spanish- and French-written publications from February 1987 to March 2020 reporting cases of DPP using the following databases: PubMed, Scielo, ScienceDirect, Google Scholar, The Cochrane Library, Open Grey, The Grey Literature Report, Clinicaltrials.gov and International Clinical Trial Registry Platform of the World Health Organization.ResultsIn total, 538 DPP were identified from 90 articles. Their clinical presentations were often severe, and the majority exhibited acute kidney failure (91.8%) with a median initial serum creatinine level of 873 μmol/L; 50.7% had alveolar haemorrhage. Other manifestations were present in 30.3% of DPP, mainly ear, nose, throat and articular manifestations. ANCAs were predominantly directed against MPO (n = 377/523; 72.1%) compared to PR3 (n = 107/523; 20.5%), with rare cases of triple positivity (n = 15/538; 2.9%). Although most patients received initial immunosuppressive therapy (n = 285/317; 89.9%), the one-year overall, renal and relapse-free survival rates were 64.8%, 38.7% and 71.1%, respectively.ConclusionDPP are associated with the characteristics of two eponymous vasculitis types, responsible for a poor overall and renal prognosis. Thus, simultaneous testing of both antibodies and systematic renal biopsy should be recommended in every patient with rapidly progressive glomerulonephritis to recognize this difficult-to-treat and rare disease.     

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

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Laparoscopic Ileocolic Resection for Crohn's Disease Associated With Midgut Malrotation

Midgut malrotation is an anomaly of fetal intestinal rotation. Its incidence in adults is rare. A case of midgut malrotation in a 51-year-old man with complicated Crohn''s disease of the terminal ileum is presented. Symptoms, diagnosis, and treatment are reviewed. Preoperative workup led to correct surgical planning that ultimately allowed a successful laparoscopic resection.     

Accuracy of computerized tomography for the evaluation of mandibular sites prior to implant placement

The objective of the present study was to observe the effect of positioning of the mandible on the accuracy of cross-sectional images obtained by reformatting computerized tomographic (CT) scans. An additional aim was to evaluate the ability of a software program (DentalVox, Era Scientific) to reconstruct these measurements on the reformatted images, regardless of the positioning of the mandible, accurately and without distortion. The test was carried out by examining a partially edentulous dry human mandible with an acrylic radiologic template. Through the use of an acrylic glass support, the mandible was positioned at angles of 0, 10, 15, 20, and 30 degrees relative to the scanning gantry, and a series of CT scans was performed that provided five sets of axial images. Each set of original axial images was reformatted by the DentalVox software, used first in its basic function, which is typical of all software for axial CT measurement (control group), and again in its function of site-specific multiplanar reconstruction (test group). The results showed that the position of the mandible in relation to the CT gantry can influence the precision of the linear measurements. The error ranged from 2% to 51%. The DentalVox software allowed the reconstruction of cross-sectional images with very little distortion regardless of the mandibular position.     

Therapeutic profile of manidipine and lercanidipine in hypertensive patients

Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo runin period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator. Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion, manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems to have a more favorable tolerability profile than the latter.     

Soluble interleukin-2 receptor in hairy-cell leukemia: a reliable marker of disease

Summary The CD25 molecule, which corresponds to the p55 α chain of the interleukin-2 receptors, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-α therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722±27,001 vs. 331±145 units/ml in controls (mean±SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-α discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r=0.84,P<0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia.     

Effects of calpain inhibitor I on multiple organ failure induced by zymosan in the rat

OBJECTIVE: Zymosan enhances the formation of reactive oxygen species, which contributes to the pathophysiology of multiple organ failure. We investigated the effects of calpain inhibitor I (5, 10, or 20 mg/kg) on the multiple organ failure caused by zymosan (500 mg/kg, administered intraperitoneally as a suspension in saline) in rats. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats.INTERVENTIONS Multiple organ failure in rats was assessed 18 hrs after administration of zymosan and/or calpain inhibitor I and was monitored for 12 days (for loss of body weight and mortality rate). MEASUREMENT AND MAIN RESULTS: Treatment of rats with calpain inhibitor I (5, 10, or 20 mg/kg intraperitoneally, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Calpain inhibitor I also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in myeloperoxidase activity and malondialdehyde concentrations caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine and for poly(adenosine-disphosphate-ribose) revealed positive staining in lung, liver, and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine and poly(adenosine-disphosphate-ribose) was reduced markedly in tissue sections obtained from zymosan-treated rats administered calpain inhibitor I (20 mg/kg intraperitoneally). Furthermore, treatment of rats with calpain inhibitor I significantly reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lung, liver, and intestine. CONCLUSION: This study provides the first evidence that calpain inhibitor I attenuates the degree of zymosan-induced multiple organ failure in the rat.