Effectiveness of first and second-line empirical treatment in Italy: Results of the European registry on Helicobacter pylori management.

Background and aims: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg). Methods: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance. Results: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events. Conclusions: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment

HCV+ Hepatocytes Induce Human Regulatory CD4+ T Cells through the Production of TGF-β

Background: Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4 + regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. Methodology/Principal Findings: HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4 + T cells. The production of IFN-c was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4 + T cells in contact with Huh7.5-FL expressed an increased level of the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV + hepatocytes upregulated the production of TGF-b and blockade of TGF-b abrogated Treg phenotype and function. Conclusions/Significance: These results demonstrate that HCV infected hepatocytes are capable of directly inducing Tregs development and may contribute to impaired host T cell responses

Adults with autism overestimate the volatility of the sensory environment.

Insistence on sameness and intolerance of change are among the diagnostic criteria for autism spectrum disorder (ASD), but little research has addressed how people with ASD represent and respond to environmental change. Here, behavioral and pupillometric measurements indicated that adults with ASD are less surprised than neurotypical adults when their expectations are violated, and decreased surprise is predictive of greater symptom severity. A hierarchical Bayesian model of learning suggested that in ASD, a tendency to overlearn about volatility in the face of environmental change drives a corresponding reduction in learning about probabilistically aberrant events, thus putatively rendering these events less surprising. Participant-specific modeled estimates of surprise about environmental conditions were linked to pupil size in the ASD group, thus suggesting heightened noradrenergic responsivity in line with compromised neural gain. This study offers insights into the behavioral, algorithmic and physiological mechanisms underlying responses to environmental volatility in ASD

Year in review in Intensive Care Medicine 2009: II. Neurology, cardiovascular, experimental, pharmacology and sedation, communication and teaching

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Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Non-linear dynamics and stability of circular cylindrical shells containing flowing fluid, part II: Large-amplitude vibrations without flow

The non-linear response of empty and fluid-filled circular cylindrical shells to harmonic excitations is investigated. Both modal and point excitations have been considered. The model is suitable to study simply supported shells with and without axial constraints. Donnell´s non-linear shallow-shell theory is used. The boundary conditions on radial displacement and the continuity of circumferential displacement are exactly satisfied. The radial deflection of the shell is expanded by using a basis of seven linear modes. The effect of internal quiescent, incompressible and inviscid fluid is investigated. The equations of motion, obtained in Part I of this study, are studied by using a code based on the collocation method. The validation of the present model is obtained by comparison with other authoritative results. The effect of the number of axisymmetric modes used in the expansion on the response of the shell is investigated, clarifying questions open for a long time. The results show the occurrence of travelling wave response in the proximity of the resonance frequency, the fundamental role of the first and third axisymmetric modes in the expansion of the radial deflection with one longitudinal half-wave, and limit cycle responses. Modes with two longitudinal half-waves are also investigated

Non-linear dynamics and stability of circular cylindrical shells conveying flowing fluid

The non-linear dynamics and stability of simply supported, circular cylindrical shells containing inviscid, incompressible fluid flow is analyzed. Geometric non-linearities of the shell are considered by using the Donnell's non-linear shallow shell theory. A viscous damping mechanism is considered in order to take into account structural and fluid dissipation. Linear potential flow theory is applied to describe the fluid-structure interaction. The system is discretized by Galerkin's method and is investigated by using two models: (i) a simpler model obtained by using a base of seven modes for the shell deflection, and (ii) a relatively high-dimensional dynamic model with IS modes. Both models allow travelling-wave response of the shell and shell axisymmetric contraction. Boundary conditions on radial displacement and the continuity of circumferential displacement are exactly satisfied. Stability, bifurcation and periodic responses are analyzed by means of the computer code AUTO for the continuation of the solution of ordinary differential equations. Non-stationary motions are analyzed with direct integration techniques. An accurate analysis of the shell response is performed by means of phase space representation, Fourier spectra, Poincare sections and their bifurcation diagrams. A complex dynamical behaviour has been found. The shell bifurcates statically (divergence) in absence of external dynamic loads by using the flow velocity as bifurcation parameter. Under harmonic load a shell conveying flow can give rise to periodic, quasi-periodic and chaotic responses, depending on flow velocity, amplitude and frequency of harmonic excitation. (C) 2002 Elsevier Science Ltd. All rights reserved

Nonlinear stability of circular cylindrical shells in annular and unbounded axial flow

The stability of circular cylindrical shells with supported ends in compressible, inviscid axial flow is investigated. Nonlinearities due to finite-amplitude shell motion are considered by using Donnell's nonlinear shallow-shell theory; the effect of viscous structural damping is taken into account. Two different in-plane constraints are applied at the shell edges: zero a-vial force and Zero axial displacement; the other boundary conditions are those for simply supported shells. Linear potential flow theory, is applied to describe the fluid-stricture interaction. Both annular and unbounded external flow are considered by using two different sets of boundary conditions for the flow beyond the shell length: (i) a flexible wall of infinite extent in the longitudinal direction, and (ii) rigid extensions of the shell (baffles). The system is discretized by the Galerkin method and is investigated by using a model involving seven degrees-of-freedom, allowing for traveling-wave response of the shell and shell axisymmetric contraction. Results for both annular and unbounded external flow show that the system loses stability by divergence through strongly subcritical bifurcations. Jumps to bifurcated states can occur well before the onset of instability predicted by linear theory, showing that a linear study of shell stability is not sufficient for engineering applications