Summary
Background
Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti‐TNF alpha. Patients with severe skin lesions unresponsive ...to topical therapy need to withdraw from treatment.
Aim
To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti‐TNF alpha and to analyse its clinical correlates.
Methods
A retrospective cohort study on all IBD patients who started anti‐TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time‐dependent predictors were updated at each available time point.
Results
Four hundred and two patients were included. Participants contributed a total of 839 person‐years of follow‐up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person‐years. Cox‐regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36–4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12–0.92; P = 0.03).
Conclusions
Paradoxical psoriasis is a relevant side effect of anti‐TNF alpha therapy, with an incidence rate of five per 100 person‐years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti‐TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of ...comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes.
Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint.
A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint).
Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faecal route.
Abstract Trimethyltin chloride (TMT) is known to produce neuronal damage in the rat hippocampus, especially in the CA1 /CA3 subfields, together with reactive astrogliosis. Previous studies indicate ...that in cultured rat hippocampal neurons the Ca2+ cytosolic increase induced by TMT is correlated with apoptotic cell death, although some molecular aspects of the hippocampal neurodegeneration induced by this neurotoxicant still remain to be clarified. Cathepsin D (Cat D) is a lysosomal aspartic protease involved in some neurodegenerative processes and also seems to play an important role in the processes that regulate apoptosis. We investigated the specific activity and cellular expression of Cat D in the rat hippocampus in vivo and in cultured organotypic rat hippocampal slices. The role of Cat D in cell death processes and the mechanisms controlling Cat D were also investigated. Cat D activity was assayed in hippocampus homogenates of control and TMT-treated rats. In order to visualize the distribution of Cat D immunoreactivity in the hippocampus, double-label immunofluorescence for Cat D and Neu N, GFAP, OX42 was performed. In addition, in order to clarify the possible relationship between Cat D activity, neuronal calcium overload and neuronal death processes, organotypic hippocampal cultures were also treated with a Cat D inhibitor (Pepstatin A) or Calpain inhibitor (Calpeptin) or an intracellular Ca2+ chelator (BAPTA-AM) in the presence of TMT. TMT treatment in rat hippocampus induced high levels of Cat D activity both in vivo and in vitro , in glial cells and in CA3 neurons, where a marked TMT-induced neuronal loss also occurred. Cat D is actively involved in CA3 neuronal death and the protease increase is a calcium-Calpain dependent phenomenon.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Highlights • AQP4 over-expression in perivascular astrocytes of the rat hippocampus and cortex. • IgG leakage in the hippocampal and cortical paravasal parenchyma of TMT-treated rats. • Enhanced ...neuronal VEGF/VEGFR-2 production and VEGFR-2 activation (VEGFR-2P).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Background
Histological involvement of surgical resection margins in Crohn’s Disease (CD) is considered an important risk factor for disease recurrence after surgery. The extent of resection ...is currently left to preoperative investigations and surgeon's experience. Aim of the study is to evaluate usefulness of intra-operative ultrasonography (IOUS) of the small bowel to best identify the surgical site of resection and reduce the risk of histological involvement of resection margins.
Methods
Consecutive patients who underwent surgery for CD (ileocaecal or ileal resections for first or repeated surgery) from April 2022 to April 2023 were prospectively enrolled (IOUS group). All patients underwent to IOUS through a small mini-laparotomy with a linear wireless probe performed by an expert gastroenterologist and the location of the proximal ileal resection was decided considering the absence of intraoperative small bowel ultrasonographic signs of CD (wall thickness, mucosal, submucosal and muscular layer thickness, echogenicity of the wall stratification and mesenteric fat). A control group from the historical cohort of patients undergoing the same surgical procedures was included; for whom the site of the proximal ileal resection was decided only on the basis of the absence of macroscopic signs of disease as usually assessed.
To minimize the selection bias, a propensity score analysis was performed identifying a subgroup of the historical cohort (non-IOUS group) matched for location of disease and repeated surgery.
The primary endpoint was histological involvement of the resection margins, judged positive in case of granulomas or signs of active ulcerative inflammation.
Results
27 patients (59% male, mean age 39.3 y SD 16.5, mean BMI 21.24 SD 2.03) were consecutively enrolled in the IOUS group. A 1:1 propensity score matching analysis was performed identifying 27 patients included in the non-IOUS group .
The two groups were homogeneous in terms of gender, age, smoking, BMI, behavior of disease and surgical technique (laparoscopic or open technique).
IOUS group presented a lower rate of histological positive margins compared to the non-IOUS group (18.5% vs 48.1% p = 0.021).
No significant differences were found in terms of mean duration of surgery between the two groups (254.2 min vs 225 min 49.3-77.8; p = 0.11) or in terms of mean length of surgical specimen (24.1 cm vs 34.1 cm SD 13.5 -23.1; p = 0.058)
Conclusion
IOUS of the small bowel appears to be a useful tool for IBD-surgeon in order to obtain a lower rate of histologically positive margins with a comparable duration of the surgery and no significant difference in length of the intestinal specimen.
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