Thrombosis of a Superior Mesenteric Vein Aneurysm: Transarterial Thrombolysis and Transhepatic Aspiration Thrombectomy

We report the case of a 31-year-old woman presenting with abdominal pain due to acute thrombosis of a superior and inferior mesenteric vein aneurysm, which was treated by a combination of arterial thrombolysis and transhepatic thrombus aspiration. At the last follow-up CT, 21 months following this procedure, there was no evidence of rethrombosis, and the patient continues to do well under oral anticoagulation. The literature regarding these uncommon mesenteric vein aneurysms without portal vein involvement, as well as their treatment options, is reviewe

The steps to therapeutic drug monitoring: A structured approach illustrated with imatinib

Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods

Thrombosis of a Superior Mesenteric Vein Aneurysm: Transarterial Thrombolysis and Transhepatic Aspiration Thrombectomy

We report the case of a 31-year-old woman presenting with abdominal pain due to acute thrombosis of a superior and inferior mesenteric vein aneurysm, which was treated by a combination of arterial thrombolysis and transhepatic thrombus aspiration. At the last follow-up CT, 21 months following this procedure, there was no evidence of rethrombosis, and the patient continues to do well under oral anticoagulation. The literature regarding these uncommon mesenteric vein aneurysms without portal vein involvement, as well as their treatment options, is reviewe

Healthcare-associated infections and antibiotic use in long-term care residents from two geographical regions in Switzerland.

The burden of healthcare-associated infections (HAIs) and antimicrobial use in Swiss long-term care facilities (LTCFs) is currently unknown. This study assessed the prevalence of HAIs and antibiotic use among LTCF residents in Switzerland. A point-prevalence study was undertaken in LTCFs in eastern and western Switzerland from August to October 2019 according to the 'Healthcare-associated infections in long-term care facilities' (HALT) protocol. Characteristics of residents (age, sex, wounds, dementia, indwelling catheters) and institutions (specific factors, geographic region) were assessed. LTCF residents were screened for HAIs and current antibiotic treatment. Personal and institutional factors associated with HAIs were assessed. In total, 1185 residents from 16 LTCFs (eight per geographic region) were screened for HAIs and antibiotic treatment. Median age was 87 years (interquartile range 79-91) and 71% were female. The prevalence of HAIs was 4.2% (west 4.3% vs east 4.2%; P=0.93), with mucocutaneous skin infections (36%) and respiratory tract infections (30%) being the most common. Independent risk factors for the presence of HAIs were presence of a chronic wound [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.0; P=0.02] and being immobile (OR 1.8, 95% CI 1.0-3.3; P=0.04). Antibiotics were given to 2.9% of residents (west 3.9% vs east 1.8%; P=0.05) on the day of the survey. The most commonly prescribed antibiotics were amoxicillin-clavulanic acid and quinolones. The prevalence of HAIs in Swiss LTCFs is similar to that in other European countries, whereas antibiotic consumption is lower. Further point-prevalence surveys on a broader scale are recommended to improve understanding of the burden of HAIs and antibiotic consumption in this setting

PathOrganic – Risks and Recommendations Regarding Human Pathogens in Organic Vegetable Production Chains

PathOrganic assesses risks associated with the consumption of fresh and minimally processed vegetables due to the prevalence of bacterial human pathogens in plant produce. The project evaluates whether organic production poses a risk on food safety, taking into consideration sources of pathogen transmission (e.g. animal manure). The project also explores whether organic versus conventional production practices may reduce the risk of pathogen manifestation. In Europe, vegetable-linked outbreaks are not well investigated. A conceptual model together with novel sampling strategies and specifically adjusted methods provides the basis for large-scale surveys of organically grown plant produce in five European countries. Critical control points are determined and evaluated and factors contributing to a food safety problem are analyzed in greenhouse and field experiments. The project aims at developing a quantitative risk assessment model and at formulating recommendations for improving food safety in organic vegetable production

Field Theory of Fluctuations in Glasses

We develop a field-theoretical description of dynamical heterogeneities and fluctuations in supercooled liquids close to the (avoided) MCT singularity. Using quasi-equilibrium arguments we eliminate time from the description and we completely characterize fluctuations in the beta regime. We identify different sources of fluctuations and show that the most relevant ones are associated to variations of "self-induced disorder" in the initial condition of the dynamics. It follows that heterogeneites can be describes through a cubic field theory with an effective random field term. The phenomenon of perturbative dimensional reduction ensues, well known in random field problems, which implies an upper critical dimension of the theory equal to 8. We apply our theory to finite size scaling for mean-field systems and we test its prediction against numerical simulations

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data

Background: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). Methods: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. Results: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Conclusions: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data.

BACKGROUND: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). METHODS: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. RESULTS: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. CONCLUSIONS: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions

Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02)

Background: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. Patients and methods: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m2 and docetaxel (Taxotere) 75 mg/m2 on days 1 and 22, followed by radiotherapy of 45 Gy (25 × 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m2 and docetaxel 20 mg/m2 weekly for 5 weeks, followed by surgery. Results: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. Conclusions: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigatio