Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI

Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-α-enolase/low anti-annexin AI IgG2 and patients with low anti-α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum

A cross-sectional study evaluating hospitalization rates for chronic limb-threatening ischemia during the COVID-19 outbreak in Campania, Italy

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 +/- 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32-0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Surgical rescue of guidewire in-stent entrapment during coronary angioplasty

During a percutaneous coronary procedure, the device may become stuck and break in the coronary circulation. This complication occurs in 0.1% of all procedures. Even with technological improvements, this event still happens because percutaneous coronary interventions are frequently used to treat complex lesions. We report a case of a patient undergoing a percutaneous stenting procedure in which the 0.014″ guidewire was caught in the right coronary artery. Removal of the guidewire was impossible, and it broke in the brachiocephalic artery. Emergency coronary artery bypass grafting was performed

Rhabdomyolysis after bariatric surgery: A multicenter, prospective study on incidence, risk factors, and therapeutic strategy in a cohort from South Italy

Background At present, prospectively collected data on rhabdomyolysis (RML) after bariatric surgery are limited. Objectives To evaluate the incidence, risk factors, and therapeutic strategy of RML in different bariatric procedures. Setting University hospitals, Italy. Methods Obese patients were prospectively enrolled. Preoperative demographic characteristics and clinical data, as well as type of anesthesia and type and total duration of surgery, were recorded as potential risk factors for RML. RML was defined as postoperative creatine kinase (CK)>1000 U/L. Incidence, possible risk factors, and therapeutic outcome of RML were assessed and compared with comparative groups. Results Four hundred eighty obese patients were included in the study. After surgery, RML was diagnosed in 62 (12.9%) patients. Muscular pain was present in 12 patients (19.3%). In RML patients, mean CK value was 1346±2132.5 U/L (range 1191-37,400). Only duration of surgery was identified as an independent risk factor for RML (P230 minutes. CK testing should be performed in all patients after bariatric surgery to make an early diagnosis and properly start fluids and diuretics

Coexistence of Different Circulating Anti-PodocyteAntibodies in Membranous Nephropathy

19openopenCorrado Murtas; Maurizio Bruschi; Giovanni Candiano; Gabriella Moroni; Riccardo Magistroni; Andrea Magnano; Francesca Bruno; Antonella Radice; Luciana Furci; Lucia Argentiero;| Maria Luisa Carnevali;| Piergiorgio Messa; Francesco Scolari; Renato Alberto Sinico; Loreto Gesualdo; Fernando C. Fervenza; Landino Allegri; Pietro Ravani; Gian Marco GhiggeriCorrado, Murtas; Maurizio, Bruschi; Giovanni, Candiano; Gabriella, Moroni; Riccardo, Magistroni; Andrea, Magnano; Francesca, Bruno; Antonella, Radice; Luciana, Furci; Lucia, Argentiero; | Maria Luisa, Carnevali; | Piergiorgio, Messa; Scolari, Francesco; Renato Alberto, Sinico; Loreto, Gesualdo; Fernando C., Fervenza; Landino, Allegri; Pietro, Ravani; Gian Marco, Ghigger

Does helicobacter pylori infection have influence on outcome of laparoscopic sleeve gastrectomy for morbid obesity?

AbstractIntroductionAmong the surgical procedures for treatment of morbid obesity, laparoscopic sleeve gastrectomy has known widespread diffusion in the last years, although it is not free from significant morbidity rates. Aim of this work is to evaluate the incidence of Helicobacter pylori (HP) infection on the postoperative outcome of patients undergoing laparoscopic sleeve gastrectomy.MethodsBetween January 2008 and December 2013, 184 patients (65 males, 119 females), mean age 35.8 ± 5.7 years, affected with morbid obesity, mean BMI 46.6 ± 6.7, underwent laparoscopic sleeve gastrectomy. All the specimens at the end of the operation were analysed by the same pathologist. Histological grading was based on the Sidney classification.ResultsSeventy-two of the patients (39.1%) were HP positive, while 112 (60.9%) were negative. No significant differences were observed between the HP+ and HP− group in terms of age, sex, weight, BMI, incidence of comorbidities and duration of follow-up. All the operations were completed via laparoscopic approach. No mortality was observed. Postoperative complications occurred in 5 patients (2.7%): three leaks (1.6%), all in the HP- group and two bleedings (1.1%), one in the HP+ and one in the HP− group. In two cases a reintervention was necessary. No significant differences were observed in the morbidity rates between the two groups. Overall mean excess weight loss at 6 months, 12 months and 24 months was respectively 47.4 ± 11.3%, 61.1 ± 12.4% and 68.4 ± 13.5%, with no significant differences between the HP+ and HP− groups.ConclusionsHP infection seems not to influence postoperative outcome of patients operated of laparoscopic sleeve gastrectomy

Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

Background and objectives: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS