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Introduction: Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways., Methods: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators., Results: In the presence of tetrodotoxin (TTX), HBB and atropine 1 μM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses., Conclusions: This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin., Competing Interests: Declaration of competing interest Sara Traserra received salary from the Universitat Autònoma de Barcelona, which is funded by a Sanofi grant. Luis Gerardo Alcalá-González, Claudia Barber, Stefania Landolfi and Carolina Malagelada declared no conflict of interest. Maura Corsetti is a consultant for Sanofi and co-chief investigator of a Sanofi-sponsored research grant. Marcel Jimenez received a research grant from Sanofi. Robert Lange is currently a Sanofi employee and may hold shares and/or stock options in the company. Sylvie Forestier is a former employee at Sanofi., (Copyright © 2024. Published by Elsevier B.V.)

Novel coronavirus disease infection (coronavirus disease 2019, COVID-19) was declared a global pandemic in March 2020 and since then has become a major public health problem. The prevalence of COVID-19 infection and acute kidney injury (AKI) is variable depending on several factors such as race/ethnicity and severity of illness. The pathophysiology of renal involvement in COVID-19 infection is not entirely clear, but it could be in part explained by the viral tropism in the kidney parenchyma. AKI in COVID-19 infection can be either by direct invasion of the virus or as a consequence of immunologic response. Diverse studies have focused on the effect of COVID-19 on glomerulonephritis (GN) patients or the 'novo' GN; however, the effect of COVID-19 in acute tubulointerstitial nephritis (ATIN) has been scarcely studied. In this article, we present five cases with different spectrums of COVID-19 infection and ATIN that may suggest that recent diagnosis of ATIN is accompanied by a worse clinical prognosis in comparison with long-term diagnosed ATIN., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background and Study Aims: Serrated polyposis syndrome (SPS) is a condition with high risk for colorectal cancer. The Endocuff device has been shown to increase adenoma detection in the general and screening population. We aimed to ascertain whether Endocuff-assisted colonoscopy increases detection of serrated lesions in comparison with standard colonoscopy during the surveillance of patients with SPS.  METHODS:  In a multicenter randomized controlled study, patients who met SPS criteria I and/or III under surveillance (previous resection of all serrated lesions ≥ 4 mm) were consecutively randomly allocated 1:1 to Endocuff-assisted colonoscopy or standard colonoscopy, performed by expert endoscopists. The main outcome was the mean number of serrated lesions detected per patient., Results: 122 patients (standard colonoscopy n = 60; Endocuff-assisted colonoscopy n = 62; 59 % men; mean age 60.6 (standard deviation [SD] 7.5) were included at 4 centers. Baseline variables (demographic data, SPS phenotype, colorectal cancer [CRC] history, cumulative polyps, and follow-up), cecal intubation rate, and withdrawal time were similar between groups. There was no statistically significant difference between Endocuff-assisted colonoscopy and standard colonoscopy for the mean number of serrated lesions detected per patient: 5.8 (95 % confidence interval [95 %CI] 4.4 - 7.2) and 5.0 (3.9 - 6.1), respectively ( P  = 0.36). There were also no differences between Endocuff-assisted and standard colonoscopy for detection of sessile serrated lesions (mean number per patient 2.5 [1.3 - 3.6] vs. 2.0 [1.1 - 3.0], P  = 0.54) and adenomas (0.9 [0.5 - 1.3] vs. 0.5 [0.3 - 0.7], P  = 0.12)., Conclusion: Use of Endocuff-assisted colonoscopy did not significantly increase the number of serrated lesion detected per patient during surveillance of SPS., Competing Interests: M. Pellisé is a consultant for Norgine Iberia; has received fees for conferences from Norgine, Olympus, and Casen Recordati; and receives an editorial fee from Thieme. Other authors do not have any conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Cutaneous lesions of sarcoidosis can allow physicians to establish the diagnosis of a systemic disease, but the need of monitoring patients presenting skin limited sarcoidosis in order to detect further extracutaneous involvement has rarely been evaluated., Objectives: To review clinical and histological features of patients with cutaneous sarcoidosis and the risk of progression to systemic disease. To characterize the phenotype of patients with isolated cutaneous sarcoidosis and to assess the temporal relationship between cutaneous and systemic disease., Methods: Retrospective review of a series of patients with cutaneous sarcoidosis. Clinical, histopathological, and evolutive features were reviewed., Results: Forty patients were included in the study. Systemic disease was present in 82.5% of patients. Previous or concurrent cutaneous involvement occurred in 81.8% of them. Seven out of 14 patients with cutaneous lesions evolved to a systemic sarcoidosis in a mean time of 6 years, with a range between 4 and 9 years. No clinical or histological differences were found between patients with systemic sarcoidosis and those who showed persistent isolated cutaneous lesions., Conclusions: Sarcoidosis may be manifested as an isolated cutaneous disorder. No clinical or histopathological features seem to be helpful to discriminate cases of a persistent isolated cutaneous disease from those that will develop systemic involvement. Since the development of systemic involvement in cases of isolated cutaneous sarcoidosis can occur many years afterward, careful monitoring seems advisable, and a long follow-up is recommended., (© 2018 The International Society of Dermatology.)

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Background: Proliferative inflammatory atrophy (PIA) has been involved in prostatic carcinogenesis. However, little is known about the clinical significance of a PIA finding in prostatic biopsies (PBs). The aim of this study is to determine the incidence of prostate inflammatory atrophy (PIA) in prostate biopsies (PBs), its association to high-grade prostatic intraepithelial neoplasia (HGPIN), prostate cancer (PCa), and tumor aggressiveness., Methods: Prospective and observational study of PIA lesion in 528 extended PBs and 200 radical prostatectomy specimens (RPS)., Outcome Measurements: PIA, HGPIN, PCa incidence, Gleason score, clinical and pathologic tumor stage and insignificant tumor rate. Univariate and multivariate analysis., Results: Overall incidence of PIA and HGPIN was 30.3% and 54%. In RPS, the incidence was 30.5% and 72%, respectively. No significant association was found between PIA and HGPIN. Overall PCa detection rate in PBs was 38.1%. PCa was found in 27.5% PBs with PIA and 42.7% of those without PIA, P < 0.001. In contrast, PCa was detected in 50.9% of PBs with HGPIN and 23% of those without HGPIN, P = 0.001. Multivariate analysis revealed that PIA decreased the risk of PCa, OR:0.59 (95%CI:0.37-0.95), P = 0.029, while HGPIN increased OR:3.16 (95%CI:2.04-4.90), P = 0.001. PIA was not related to Gleason grade and clinical stage, however it was associated to an insignificant tumors increase, OR:3.08 (95%CI:1.09-8.7), P = 0.033. The information in RPS suggests that PIA is associated with less aggressive tumors and a higher probability of insignificant tumors., Conclusions: PIA is present in one third of PBs, HGPIN in one half of them, and no association exists between both lesions. Contrary to HGPIN, PIA finding is associated to lower risk of PCa detection. Tumors accompanying PIA seem to be less aggressive and have a greater probability of being insignificant., (© 2015 Wiley Periodicals, Inc.)

We aimed to compare immunoreactivity patterns of four different anti-α-syn antibodies in surgical specimens of the gastrointestinal tract of Parkinson disease and control cases. Surgical specimens from stomach, small and large bowel of 6 PD cases and 12 controls were studied. Primary antibodies: anti-α-syn clone KM51, anti-phosphorylated α-syn Ser129, anti-α-syn clone 15G7 and anti-nitrated α-syn505. We found different immunoreactivity patterns: (a) coarse, Lewy-body-like aggregates labelled by the 4 antibodies and detected in 4/6 PD cases and in 1/12 controls; (b) distinct punctate cytoplasmic staining of ganglion cells labelled by anti-phosphorylated-α-syn and detected in 3/6 PD cases and 3/12 controls; (c) fine diffuse, synaptic-type staining of neural structures labelled by anti-α-syn-15G7 and anti-nitrated-α-syn505 and detected in all subjects. We conclude that different specific and non-specific immunoreactivity patterns are detected in surgical specimens of gastrointestinal tract when using different anti-α-syn antibodies, as they recognize different epitopes and states of alpha-synuclein protein. Coarse aggregates in neural structures seem to be the most promising marker for the diagnosis of Lewy-body parkinsonism when evaluating abnormal α-syn in the gastrointestinal tract., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Inhibition of tumor necrosis fact (TNFalpha) is of potential benefit in the treatment of chronic inflammatory conditions. However, TNFalpha plays an important role in host defenses against infection, and blocking TNFalpha production may also have adverse effects. We tested the efficacy and safety of anti-TNFalpha therapy in experimental colitis induced by trinitrobenzenesulfonic acid. We cultured colonic wall specimens for bacterial growth and measured native TNFalpha protein synthesis in colonic tissue at days 0, 1, 4, 10 and 18 after induction of colitis. Anti-TNFalpha therapy (monoclonal g1 immunoglobulin, 15 mg/kg i.p., every third day) was started on either day 4 or day 10 after induction of colitis. On day 18, we measured the release of inflammatory mediators and scored colonic lesions. In acute lesions, several species of the common flora were grown, including Streptococcus, Staphylococcus, Bacteroides, clostridia and enterobacteria. In chronic lesions, only enterobacteria, clostridia and lactobacilli were isolated. TNFalpha production by inflamed colonic tissue was increased in both acute and chronic lesions. Anti-TNFalpha therapy induced a significant decrease in the release of inflammatory mediators and histopathological remission when treatment started on day 10. However, anti-TNFalpha therapy increased eicosanoid release and lesion scores when treatment started on day 4. In conclusion, acute colonic lesions showed polymicrobial infection. Anti-TNFalpha therapy induced remission of chronic intestinal inflammation, but early treatment did not prove effective.