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Significance Statement Approximately 20% of patients with lupus nephritis, the most common renal manifestation of systemic lupus erythematosus, show membranous lupus nephritis on kidney biopsy, and nearly 10% eventually develop ESKD. Recently, two proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), were shown to be present in a subset of membranous lupus nephritis kidney biopsy specimens. In an examination of 374 membranous lupus nephritis kidney biopsy specimens, the authors found 32.6% to be EXT1/EXT2-positive. Kidney biopsy specimens from patients with EXT1/EXT2-positive membranous lupus nephritis showed less chronicity features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) compared with those from EXT1/EXT2-negative patients. EXT1/EXT2-negative patients were also more likely to reach ESKD than EXT1/EXT2-positive patients. These findings suggest that the presence of EXT1/EXT2 is favorable, and that EXT1/EXT2-positive patients have better renal outcomes compared with EXT1/EXT2-negative patients. Background In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis. Methods We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared. Results Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger ( P =0.01), had significantly lower serum creatinine levels ( P =0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h ( P =0.009), and had significantly less chronicity features (glomerulosclerosis, P =0.001 or interstitial fibrosis and tubular atrophy, P <0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P= 0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P =0.003). Conclusions The prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.

BACKGROUND: Surgical treatment for transverse colon cancer involves either extended colectomy or segmental resection, depending on the location of the tumor and surgeon perspective. However, the oncological safety of segmental resection has not yet been established in large cohort studies. OBJECTIVE: This study aims to compare segmental resection versus extended colectomy for transverse colon cancer in terms of oncological outcomes. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted using a nationwide cohort. PATIENTS: A total of 66,062 patients who underwent colectomy with curative intent for transverse stage I to III adenocarcinoma were identified in the National Cancer Database (2004–2015). MAIN OUTCOME MEASURES: Patients were divided in 2 groups based on the type of surgery received (extended versus segmental resection). The primary outcome was overall survival. Secondary outcomes were 30- and 90-day mortality, length of hospital stay, and readmission rate within 30 days of surgical discharge. RESULTS: Extended colectomy was performed in 44,417 (67.2%) patients, whereas 21,645 (32.8%) patients underwent segmental resection. Extended colectomy was associated with lower survival at multivariate analysis (HR, 1.07; 95% CI, 1.04–1.10; p < 0.001). The subgroup analysis showed that extended resection was independently associated with poorer survival in mid transverse colon cancers (HR, 1.08; 95% CI, 1.04–1.12; p < 0.001) and in stage III tumors (HR, 1.11; 95% CI, 1.04–1.18; p < 0.001). The number of at least 12 harvested lymph nodes was an independent predictor of improved survival in both overall and subgroup analyses. LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Extended colectomy was not associated with a survival advantage compared with segmental resection. On the contrary, extended colectomy was associated with slightly poorer survival in mid transverse cancers and locally advanced tumors. Segmental resection was found to be safe when appropriate margins and adequate lymph node harvest were achieved. See Video Abstract at http://links.lww.com/DCR/B454. ABORDAJE QUIRÚRGICO DEL CÁNCER DE COLON TRANSVERSO: ANÁLISIS DE LA PRÁCTICA ACTUAL Y LOS RESULTADOS ONCOLÓGICOS UTILIZANDO LA BASE DE DATOS NACIONAL DE CÁNCER ANTECEDENTES: El tratamiento quirúrgico para el cáncer de colon transverso implica colectomía extendida o resección segmentaria, según la ubicación del tumor y la perspectiva del cirujano. Sin embargo, la seguridad oncológica de la resección segmentaria aún no se ha establecido en estudios de cohortes grandes. OBJETIVO: Este estudio tiene como objetivo comparar la resección segmentaria versus la colectomía extendida para el cáncer de colon transverso en términos de resultados oncológicos. DISEÑO: Este fue un estudio de cohorte retrospectivo. ESCENARIO: Este estudio se realizó utilizando una cohorte a nivel nacional. PACIENTES: Un total de 66,062 pacientes que se sometieron a colectomía con intención curativa por adenocarcinoma de colon transverso en estadio I-III fueron identificados en la Base de Datos Nacional del Cáncer (2004-2015). PRINCIPALES MEDIDAS DE RESULTADO: Los pacientes se dividieron en dos grupos según el tipo de cirugía recibida (resección extendida versus resección segmentaria). El resultado primario fue la supervivencia global. Los resultados secundarios fueron la mortalidad a los 30 y 90 días, la duración de la estancia hospitalaria y la tasa de reingreso dentro de los 30 días posteriores al alta quirúrgica. RESULTADOS: Se realizó colectomía extendida en 44,417 (67.2%) casos, mientras que 21,645 (32.8%) pacientes fueron sometidos a resección segmentaria. La colectomía extendida se asoció con una menor supervivencia en el análisis multivariado (HR 1.07 IC 95% 1.04-1.10; p <0.001). El análisis de subgrupos mostró que la resección extendida se asoció de forma independiente con una menor supervivencia en los cánceres de colon transverso medio (HR 1.08 IC 95% 1.04-1.12; p <0.001) y en tumores en estadio III (HR 1.11 IC 95% 1.04-1.18; p <0.001). Un número de al menos 12 ganglios linfáticos cosechados fue un predictor independiente de una mejor supervivencia en los análisis general y de subgrupos. LIMITACIONES: Este estudio estuvo limitado por su diseño retrospectivo. CONCLUSIÓN: La colectomía extendida no se asoció con una ventaja de supervivencia en comparación con la resección segmentaria. Por el contrario, la colectomía extendida se asoció con una supervivencia levemente menor en cánceres de colon transverso medio y tumores localmente avanzados. Se encontró que la resección segmentaria es segura cuando se logran los márgenes apropiados y la cosecha adecuada de ganglios linfáticos. Consulte Video Resumen en http://links.lww.com/DCR/B454.

Abstract A 40-yr-old male with no significant past medical history presented with sudden onset right-sided retro-orbital headache associated with vision loss after a session of strenuous exercise. Initial assessment with noncontrast head computed tomography at the local emergency department revealed a right sided occipital intracranial hemorrhage (ICH). On arrival the patient ad a left quadrantopsia with Glasgow Coma Scale of 15 and an ICH score of 0. A computed tomographic angiography showed a high density 6 × 9 mm vascular lesion associated with 2 tortuous vessels. Cerebral angiography revealed a right sided dural arteriovenous fistula, Cognard Type IV, with arterial feeders arising from dural branches of the right vertebral artery, the posterior division of the right middle meningeal artery and meningeal branches distal to the neuromeningeal trunk of the left ascending pharyngeal artery. 1 Four days after the ICH event the patient was treated with endovascular Onyx embolization of the fistula, through a transradial approach. Immediate angiographic assessment showed complete obliteration of the dAVF. The patient was discharged home and recovered his visual field deficit over 3 mo. The following operative video includes a discussion of the endovascular technique and treatment nuances associated with the transarterial management of a dural arteriovenous fistula. Patient consent was given prior to the procedure and consent and approval for this operative video was waived due to the retrospective nature of this manuscript and the anonymized video material.

Abstract Wide-necked aneurysms often pose challenges for distal access to the distal vasculature. This 64-yr-old woman without neurological deficits presented with atypical headaches of gradual onset. MRI revealed a large, symptomatic, unruptured carotid terminus aneurysm incorporating the origin of both the middle (MCA) and anterior cerebral arteries (ACA). Its wide neck created significant risks to coil prolapse and parent vessel compromise, risking stroke. With other options of higher risks, we recommended an around-the-world technique. Standard transfemoral access was used to the right internal carotid artery (ICA) with a 6F-Shuttle sheath and intracranial carotid with a 6F-Sofia distal access catheter. With dual-microcatheter access, 1 catheter was placed in the aneurysm dome, a second in the MCA for stent placement. Advancing the wire around the aneurysm first formed a loop from the lateral to medial wall for access to the MCA. The microcatheter was then advanced around the wire into the MCA, keeping the loop within the dome. With the loop's distal tip anchored, the distal end of the stent was deployed and anchored into the MCA. Both pitfalls (ie, lack of sufficient distal access, collapse of stent device during deployment) were resolved using a balloon catheter. With the balloon positioned and inflated as the anchor, the wire and catheter were pulled together. The loop in the aneurysm's dome straightened out across the neck, the stent was advanced into the MCA, and coiling proceeded. A large neck remnant had partially closed on 6-mo follow-up angiogram. Patient consented to undergo the procedure. Illustrations in video published/printed with permission from Mayfield Clinic.

Abstract Sidewall aneurysm treatment often requires complex management strategies. These can include advanced clipping techniques or stent-assisted coiling techniques. Endovascular coiling alone has been associated with high recurrence rates and is often not feasible. 1-4 Flow-diversion embolization has recently become a standard of care for many aneurysms, demonstrating high occlusion rates. 4,5 However, the third generation of coil-assist stents can be delivered with 0.0165” microcatheters, being an ideal adjunct to manage this group of aneurysms in more distal locations. In this video, a 16-yr-old teenager with Parry-Romberg syndrome and congenital adrenal hyperplasia had an incidental finding of a 6.5-mm sidewall aneurysm arising off the angular branch of the left middle cerebral artery, found during the work-up of complex partial seizures. The patient consented to the procedure. Due to his young age and aneurysm size, a decision was made to treat the aneurysm through an endovascular approach. Under general anesthesia, a transfemoral approach was carried out using a 6-French short sheath. A 6-French guiding catheter was left in the distal cervical left internal carotid artery; a 0.0165” microcatheter was used to first deploy a 3.0 × 15 mm Neuroform Atlas stent, completely covering the length of the aneurysm. Then, the stent was traversed with the microcatheter to coil the aneurysm. Follow-up cerebral angiogram confirmed complete occlusion of the aneurysm.

Background. Glomerular size in renal allografts is impacted by donor–recipient factors and response to injury. In serial biopsies of patients with well-functioning grafts, increased glomerular size correlates with better survival. However, no previous study has addressed the association of glomerular size at the time of a for-cause biopsy and clinical/histopathologic markers of injury, or effect on long-term graft outcome. Methods. Two cohorts of kidney transplant recipients enrolled in the Deterioration of Kidney Allograft Function study were evaluated. The prospective cohort (PC, n = 581): patients undergoing first for-cause kidney biopsy 1.7 ± 1.4 (mean ± SD) y posttransplant; and the cross-sectional cohort (CSC, n = 446): patients developing new-onset renal function deterioration 7.7 ± 5.6 y posttransplant. Glomerular planar surface area and diameter were measured on all glomeruli containing a vascular pole. Kidney biopsy was read centrally in a blinded fashion according to the Banff criteria. Results. Glomerular area was significantly higher in the CSC than the PC; time from transplant to indication biopsy was associated with glomerular area in both cohorts (P values ≤ 0.001). Glomerular area was associated with indices of microvascular inflammation (glomerulitis, peritubular capillary infiltrates; P values ≤ 0.001) and segmental glomerulosclerosis (P value < 0.0001). In the CSC, higher glomerular area was associated with higher estimated glomerular filtration rate (P value ≤ 0.001) and increased graft survival after accounting for microvascular inflammation (adjusted hazard ratio = 0.967; 95% confidence interval: 0.948-0.986; hazard ratio in biopsies without evidence of diabetes or antibody mediated rejection = 0.919, 95% confidence interval: 0.856-0.987). Conclusions. Glomerular size is associated with histopathologic features present at the time of indication biopsy and with increased graft survival in the CSC.

Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.