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Here, we describe a rare case of acquired von Willebrand syndrome (VWS) associated with intracranial plasmacytoma. The literature includes reports of a few cases of plasmacytoma with central nervous involvement, but none of them with acquired VWS. Diagnosis was made based on a stereotaxic intracerebral biopsy. During this biopsy, a ventriculoperitoneal shunt was established, which was complicated with abnormal bleeding. Subsequent hemostasis assessment related to hemopathy revealed acquired von Willebrand disease. The patient received induction therapy with bortezomib, thalidomide, and dexamethasone (VTD), followed by high-dose melphalan chemotherapy and autologous stem cell transplantation, and then VTD consolidation, and finally maintenance with lenalidomide. Our patient currently remains in very good partial response without neurological symptoms after 4 months of maintenance. The patient is free of progression 14 months after their original presentation. [ABSTRACT FROM AUTHOR]

We describe a rare case of Castleman disease associated de novo with Hodgkin lymphoma. The incidence of Castleman disease is rare; only a few studies have described it in de novo association with Hodgkin lymphoma. The patient described here complained of unique evolutionary axillary adenopathy. A positron-emission tomography/computed tomography scan revealed hypermetabolic activity in this area. Diagnosis was based on a total excision biopsy of the adenopathy. The patient underwent complete remission with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy for treating Hodgkin lymphoma after surgical excision of the unicentric Castleman disease lesion. [ABSTRACT FROM AUTHOR]

Background: Waldenström's macroglobulinemia is a rare B-cell lymphoma. The gold standard treatment for Waldenström's macroglobulinemia is an anti-CD20 antibody (rituximab) in combination with alkylating agents and dexamethasone. Treatment targeting the B-cell receptor such as ibrutinib (but not idelalisib) is currently approved for treatment of patients with relapsed or refractory Waldenström's macroglobulinemia.Case Presentation: We report a case of a 71-year-old white French man with Waldenström's macroglobulinemia who presented with acute renal failure and hyperviscosity syndrome. His Waldenström's macroglobulinemia was refractory to first-line treatment with rituximab, cyclophosphamide, and dexamethasone. Because of his hemorrhagic syndrome and medical history of recent myocardial infarction, we decided to treat him with idelalisib 150 mg twice daily instead of ibrutinib. We observed a very quick improvement in the patient's clinical status without need for dose adjustment.Conclusion: Our patient's case provides the first evidence, to the best of our knowledge, that idelalisib may be an efficient treatment option for patients with Waldenström's macroglobulinemia complicated by anuric renal failure and in whom ibrutinib is contraindicated. [ABSTRACT FROM AUTHOR]

Marfan syndrome is a connective tissue disease that rarely presents first with peripheral aortic aneurysms. We highlight the case of a young man with Marfan syndrome presenting with an abdominal aortic aneurysm due to a heterozygous fibrillin-1 gene mutation., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Histological healing may be the ultimate therapeutic goal in ulcerative colitis [UC]. We investigated, for the first time, the association between vedolizumab trough levels and histological healing in UC., Methods: This is a single-centre retrospective cohort study including all consecutive UC patients on vedolizumab maintenance therapy who had a histological evaluation blindly to clinical data and underwent therapeutic drug monitoring, between June 2014 and March 2018. Per-event analysis was performed. Histological healing was defined as a Nancy histological index ≤1., Results: Thirty-five histological samples were analysed. Median [interquartile range] vedolizumab trough levels were higher in the group with histological healing (31.5 [25-49.1] μg/mL) compared with the group without histological healing (15 [9-26.6] μg/mL, p = 0.02). The higher vedolizumab trough level quartiles tended to be associated with greater rates of histological healing [p = 0.10]. A cut-off vedolizumab trough level of 25 μg/mL predicted histological healing with an accuracy of 74% and an area under the receiver operating curve of 0.62 [95% confidence interval 0.58-0.92, p = 0.004]. Bivariate analysis identified a vedolizumab trough level ≥25 µg/mL [p = 0.006], a partial Mayo score ≤1 [p = 0.008], C-reactive protein level <5 mg/L [p = 0.005] and a Mayo endoscopic subscore ≤1 [p = 0.0004] as factors associated with histological healing., Conclusions: Histological healing was associated with higher vedolizumab trough levels during maintenance therapy in UC. A vedolizumab trough level threshold of 25 μg/mL proved most optimal to predict histological healing according to the Nancy histological index. Confirmation of these data in larger, independent cohorts is needed., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Current histoprognostic parameters and prognostic scores used in paragangliomas and pheochromocytomas do not adequately predict the risk of metastastic progression and survival. Here, using a series of 147 cases of paraganglioma and pheochromocytoma, we designed and evaluated the potential of a new score, the COPPS (COmposite Pheochromocytoma/paraganglioma Prognostic Score), by taking into consideration three clinico-pathological features (including tumor size, necrosis, and vascular invasion), and the losses of PS100 and SDHB immunostain to predict the risk of metastasis. We compared also the performance of the COPPS with several presently used histoprognostic parameters in risk assessment of these tumors. A PASS score (Pheochromocytoma of the Adrenal gland Scaled Score) ≥ 6 was significantly associated with the occurrence of metastases (P < 0.0001) and shorter PFS (P = 0.013). In addition, both MCM6 and Ki-67 LI correlated with worse PFS (P = 0.004 and P < 0.0001, respectively), and MCM6, but not Ki-67, was significantly higher in metastatic group (P = 0.0004). Loss of PS100 staining correlated with the occurrence of metastasis (P < 0.0001) and shorter PFS (P < 0.0001). At a value of greater or equal to 3, the COPPS correlated with shorter PFS (P < 0.0001), and predicted reproducibly (weighted Kappa coefficient, 0.863) the occurrence of metastases with a sensitivity of 100.0% and specificity of 94.7%. It thus surpassed those found for either PASS, SDHB, MCM6, or Ki-67 alone. In conclusion, while validation is still necessary in independent confirmatory cohorts, COPPS could be of great potential for the risk assessment of metastasis and progression in paragangliomas and pheochromocytomas.

Extraintestinal manifestations in inflammatory bowel disease involve most frequently the joints, the skin, the eyes, the liver and the biliary tract. Renal involvement is rare, and manifested as nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis. In patients with inflammatory bowel disease, renal disease is most frequently due to treatment nephrotoxicity and rarely as a guenine extraintestinal manifestation of inflammatory bowel disease. We are reporting a case of tubulointerstitial nephritis as an extraintestinal manifestation of Crohn's disease and we are explaining the diagnostic difficulty to distinguish this from drug-induced nephrotoxicity., (Copyright © 2018. Published by Elsevier Masson SAS.)

Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p = 0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83-0.91) and 0.84 (0.77-0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p = 0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification.

Background and Aims: Triggering receptor expressed on myeloid cells-1 [TREM-1] is known to amplify inflammation in several diseases. Autophagy and endoplasmic reticulum [ER] stress, which activate the unfolded protein response [UPR], are closely linked and defects in these pathways contribute to the pathogenesis of inflammatory bowel disease [IBD]. Both autophagy and UPR are deeply involved in host-microbiota interactions for the clearance of intracellular pathogens, thus contributing to dysbiosis. We investigated whether inhibition of TREM-1 would prevent aberrant inflammation by modulating autophagy and ER stress and preventing dysbiosis., Methods: An experimental mouse model of colitis was established by dextran sulphate sodium treatment. TREM-1 was inhibited, either pharmacologically by LR12 peptide or genetically with Trem-1 knock-out [KO] mice. Colon tissues and faecal pellets of control and colitic mice were used. Levels of macroautophagy, chaperone-mediated autophagy [CMA], and UPR proteins were evaluated by western blotting. The composition of the intestinal microbiota was assessed by MiSeq sequencing in both LR12-treated and KO animals., Results: We confirmed that inhibition of TREM-1 attenuates the severity of colitis clinically, endoscopically and histologically. We observed an increase in macroautophagy [ATG1/ULK-1, ATG13, ATG5, ATG16L1, and MAP1LC3-I/II] and in CMA [HSPA8 and HSP90AA1], whereas there was a decrease in the UPR [PERK, IRE-1α, and ATF-6α] protein expression levels in TREM-1 inhibited colitic mice. TREM-1 inhibition prevented dysbiosis., Conclusions: TREM-1 may represent a novel drug target for the treatment of IBD, by modulating autophagy activity and ER stress., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)