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Background and objective: Previous germline studies on renal cell carcinoma (RCC) have usually pooled clear and non–clear cell RCCs and have not adequately accounted for population stratification, which might have led to an inaccurate estimation of genetic risk. Here, we aim to analyze the major germline drivers of RCC risk and clinically relevant but underexplored germline variant types. Methods: We first characterized germline pathogenic variants (PVs), cryptic splice variants, and copy number variants (CNVs) in 1436 unselected RCC patients. To evaluate the enrichment of PVs in RCC, we conducted a case-control study of 1356 RCC patients ancestry matched with 16 512 cancer-free controls using approaches accounting for population stratification and histological subtypes, followed by characterization of secondary somatic events. Key findings and limitations: Clear cell RCC patients (n = 976) exhibited a significant burden of PVs in VHL compared with controls (odds ratio [OR]: 39.1, p = 4.95e-05). Non–clear cell RCC patients (n = 380) carried enrichment of PVs in FH (OR: 77.9, p = 1.55e-08) and MET (OR: 1.98e11, p = 2.07e-05). In a CHEK2-focused analysis with European participants, clear cell RCC (n = 906) harbored nominal enrichment of low-penetrance CHEK2 variants—p.Ile157Thr (OR: 1.84, p = 0.049) and p.Ser428Phe (OR: 5.20, p = 0.045), while non–clear cell RCC (n = 295) exhibited nominal enrichment of CHEK2 loss of function PVs (OR: 3.51, p = 0.033). Patients with germline PVs in FH, MET, and VHL exhibited significantly earlier age of cancer onset than patients without germline PVs (mean: 46.0 vs 60.2 yr, p

Abstract Background Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history. Methods A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers. Results From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€). Conclusions/interpretation While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

IntroductionApolipoprotein-L1 (APOL1) is a primate-specific protein component of high-density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe-independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on a haplotype-centric model.MethodsGenomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. A quantitative PCR assay with modified forward primers and a common reverse primer enabled us to quantitatively identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion. Additionally, we used Sanger sequencing to verify our QPCR findings.ResultsOur novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletions, and homozygous SNPs/deletions, with at least 4-fold differences. A high prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, no significant impact of recipient APOL1 variants on transplant outcomes was observed up to 12-month of follow-ups. Ongoing research will encompass more time points and a larger patient cohort, allowing for a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding.ConclusionOur cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.

Central nervous system germ cell tumors are rare lesions that are more frequently seen in the pediatric age group. Intracranial germinomas are a type of these germ cell tumors and commonly arise in the pineal region, suprasellar region, or less frequently at both areas (bifocal). Common features of this tumor depend on the location of the lesion(s) and include Parinaud's syndrome, obstructive hydrocephalus, diabetes insipidus, panhypopituitarism, strabismus, and visual acuity defects. We report a case of bifocal pineal and suprasellar germinoma with posterior fossa metastases in a 15-year-old male patient. The involvement of the third ventricular floor and nonthickened inferior pituitary stalk of the suprasellar lesion suggest that it is a metastasis of a primary pineal lesion rather than a dual-primary. This distinction, with the presence of posterior fossa metastases, favors the use of more aggressive treatment with combination radiation therapy and chemotherapy for a better outcome.

Traumatic brain injury (TBI) is associated with mortality and morbidity worldwide. Accumulating pre-clinical and clinical data suggests TBI is the leading extrinsic cause of progressive neurodegeneration. Neurological deterioration after either a single moderate-severe TBI or repetitive mild TBI often resembles dementia in aged populations; however, no currently approved therapies adequately mitigate neurodegeneration. Inflammation correlates with neurodegenerative changes and cognitive dysfunction for years post-TBI, suggesting a potential association between immune activation and both age- and TBI-induced cognitive decline. Inflammaging, a chronic, low-grade sterile inflammation associated with natural aging, promotes cognitive decline. Cellular senescence and the subsequent development of a senescence associated secretory phenotype (SASP) promotes inflammaging and cognitive aging, although the functional association between senescent cells and neurodegeneration is poorly defined after TBI. In this mini-review, we provide an overview of the pre-clinical and clinical evidence linking cellular senescence with poor TBI outcomes. We also discuss the current knowledge and future potential for senotherapeutics, including senolytics and senomorphics, which kill and/or modulate senescent cells, as potential therapeutics after TBI.

We identified the effective components and the underlying mechanisms of Quince (Cydonia oblonga Mill, COM) extract against atherosclerosis. The effective components of COM extract were identified with UHPLC-Q-TOF-MS/MS. Network pharmacology was performed. A rat model of atherosclerosis induced by high-fat emulsion combined with vitamin D3 was established. The anti-atherosclerosis effect of COM extract was evaluated from various aspects such as blood lipid regulation, anti-oxidative stress, anti-inflammatory response, and vascular protection function. We identified 14 serum components of COM extract using UHPLC-Q-TOF-MS/MS. Through prediction, 573 targets were obtained, among which 224 targets were atherosclerosis specific targets. The key targets included GSK3β, ESR1, EGFR, and HSP90AA1. The key signaling pathway was PI3K-Akt signaling pathway. Pharmacodynamics analysis showed that COM extract reduced the levels of TC, TG, and LDL-C as well as ALT and AST, while increased the level of HDL-C. Mechanistically, COM extract significantly increased serum SOD and GSH-Px activities, but decreased MDA content in atherosclerosis rats, showing antioxidant effects. Meanwhile, COM extract significantly down-regulated the levels of pro-inflammatory factors IL-1β, IL-6, TNF-α and CRP, but up-regulated anti-inflammatory factor IL-10. Additionally, COM extract increased the levels of NO, eNOS, and 6-keto-PGF1α; whereas, decreased the levels of ET-1 and TXB2. Furthermore, COM extract significantly inhibited the mRNA and protein levels of EGFR, p-PI3K, p-AKT, GSK-3β, Bax, and Caspase-3 as well as the Bax/Bcl-2 ratio. Conclusively, COM extract exerts hypolipidemic, anti-oxidative, anti-inflammatory, anti-thrombotic and vascular endothelium protective effects on atherosclerosis rat model, which may be related to the inhibition of EGFR/PI3K/AKT/GSK-3β signaling pathway.

Synchronous opportunistic infections are luckily rare in people living with HIV (PLWH) in the era of highly effective antiretroviral medications. We describe the case of a middle-aged man who presented with diarrhea and shortness of breath and was found to have pneumocystis pneumonia, disseminated histoplasmosis and disseminated mycobacterium avium complex infection along with a new diagnosis of human immunodeficiency virus (HIV) infection. This case highlights that individuals who remain undiagnosed with HIV infection for a long time can still present with concurrent infections and clinicians should remain aware of this.

Abstract Aim and hypotheses The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice. Methods A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan–Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death. Results From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome. Conclusion THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5–6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 ( http://www.ENCEPP.eu ).

Measurement(s) plant trait Technology Type(s) digital curation Sample Characteristic - Organism Viridiplantae Sample Characteristic - Location Australia Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14545755

Candida albicans causes severe invasive candidiasis. C. albicans infection requires the virulence factor candidalysin (CL) which damages target cell membranes. However, the mechanism that CL uses to permeabilize membranes is unclear. We reveal that CL forms membrane pores using a unique mechanism. Unexpectedly, CL readily assembled into polymers in solution. We propose that the basic structural unit in polymer formation is a CL oligomer, which is sequentially added into a string configuration that can close into a loop. CL loops appear to spontaneously insert into the membrane to become pores. A CL mutation (G4W) inhibited the formation of polymers in solution and prevented pore formation in synthetic lipid systems. Epithelial cell studies showed that G4W CL failed to activate the danger response pathway, a hallmark of the pathogenic effect of CL. These results indicate that CL polymerization in solution is a necessary step for the damage of cellular membranes. Analysis of CL pores by atomic force microscopy revealed co-existence of simple depressions and more complex pores, which are likely formed by CL assembled in an alternate oligomer orientation. We propose that this structural rearrangement represents a maturation mechanism that stabilizes pore formation to achieve more robust cellular damage. To summarize, CL uses a previously unknown mechanism to damage membranes, whereby pre-assembly of CL loops in solution leads to formation of membrane pores. Our investigation not only unravels a new paradigm for the formation of membrane pores, but additionally identifies CL polymerization as a novel therapeutic target to treat candidiasis.

Background: Contact tracing alone is often inadequate to determine the source of healthcare personnel (HCP) COVID-19 when SARS-CoV-2 is widespread in the community. We combined whole-genome sequencing (WGS) with traditional epidemiologic analysis to investigate the frequency with which patients or other HCP with symptomatic COVID-19 acted as the source of HCP infection at a large tertiary-care center early in the pandemic. Methods: Cohort samples were selected from patients and HCP with PCR-positive SARS-CoV-2 infection from a period with complete retention of samples (March 14, 2021–April 10, 2020) at Rush University Medical Center, a 664-bed hospital in Chicago, Illinois. During this period, testing was limited to symptomatic patients and HCP. Recommended respiratory equipment for HCP evolved under guidance, including a 19-day period when medical face masks were recommended for COVID-19 care except for aerosol-generating procedures. Viral RNA was extracted and sequenced (NovaSeq, Illumina) from remnant nasopharyngeal swab samples in M4RT viral transport medium. Genomes with >90% coverage underwent cluster detection using a 2 single-nucleotide variant genetic distance cutoff. Genomic clusters were independently evaluated for valid epidemiologic links by 2 infectious diseases physicians (with a third adjudicator) using metadata extracted from the electronic medical record and according to predetermined criteria (Table 1). Results: In total, 1,031 SARS-CoV-2 sequences were analyzed, identifying 49 genomic clusters with HCP (median, 8; range, 2–43 members per cluster; total, 268 patients and 115 HCP) (Fig. 1). Also, 20,190 flowsheet activities were documented for cohort HCP and patient interactions, including 686 instances in which a cohort HCP contributed to a cohort patient’s chart. Most HCP infections were considered not healthcare associated (88 of 115, 76.5%). We did not identify any strong linkages for patient-to-HCP transmission. Moreover, 13 HCP cases (11.3%) were attributed to patient source (weak linkage). Also, 14 HCP cases (12.2%) were attributed to HCP source (11 strong and 3 weak linkages). Weak linkages were due to lack of epidemiologic data for HCP location, particularly nonclinical staff (eg, an environmental service worker who lacked location documentation to rule out patient-specific contact). Agreement for epidemiologic linkage between the 2 evaluators was high (κ, 0.91). Conclusions: Using genomic and epidemiologic data, we found that most HCP COVID-19 infections were not healthcare associated. We found weak evidence to support symptomatic patient-to-HCP transmission of SARS-CoV-2 and stronger evidence for HCP-to-HCP transmission. Large genomic clusters without plausible epidemiologic links were identified, reflecting the limited utility of genomic surveillance alone to characterize chains of transmission of SARS-CoV-2 during extensive community spread.

Background: Candida auris is an emerging multidrug-resistant yeast that is transmitted in healthcare facilities and is associated with substantial morbidity and mortality. Environmental contamination is suspected to play an important role in transmission but additional information is needed to inform environmental cleaning recommendations to prevent spread. Methods: We conducted a multiregional (Chicago, IL; Irvine, CA) prospective study of environmental contamination associated with C. auris colonization of patients and residents of 4 long-term care facilities and 1 acute-care hospital. Participants were identified by screening or clinical cultures. Samples were collected from participants’ body sites (eg, nares, axillae, inguinal creases, palms and fingertips, and perianal skin) and their environment before room cleaning. Daily room cleaning and disinfection by facility environmental service workers was followed by targeted cleaning of high-touch surfaces by research staff using hydrogen peroxide wipes (see EPA-approved product for C. auris, List P). Samples were collected immediately after cleaning from high-touch surfaces and repeated at 4-hour intervals up to 12 hours. A pilot phase (n = 12 patients) was conducted to identify the value of testing specific high-touch surfaces to assess environmental contamination. High-yield surfaces were included in the full evaluation phase (n = 20 patients) (Fig. 1). Samples were submitted for semiquantitative culture of C. auris and other multidrug-resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase–producing Enterobacterales (ESBLs), and carbapenem-resistant Enterobacterales (CRE). Times to room surface contamination with C. auris and other MDROs after effective cleaning were analyzed. Results: Candida auris colonization was most frequently detected in the nares (72%) and palms and fingertips (72%). Cocolonization of body sites with other MDROs was common (Fig. 2). Surfaces located close to the patient were commonly recontaminated with C. auris by 4 hours after cleaning, including the overbed table (24%), bed handrail (24%), and TV remote or call button (19%). Environmental cocontamination was more common with resistant gram-positive organisms (MRSA and, VRE) than resistant gram-negative organisms (Fig. 3). C. auris was rarely detected on surfaces located outside a patient’s room (1 of 120 swabs;

Abstract Background Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. Objectives To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). Methods Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. Results Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. Conclusion The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.

(1) Background: Practice guidelines define drug-eluting stents (DES) as the standard of care in coronary percutaneous coronary intervention (PCI), including in acute coronary syndrome (ACS). This is based on comparisons with bare-metal stents (BMS). However, non-drug-eluting titanium-nitride-oxide-coated stents (TiNOS) have not been taken into account. The objective of this study is to determine whether TiNOS can be used as an alternative to DES in ACS. (2) Methods: A prospective systematic literature review (SLR), conducted according to the PRISMA guidelines, was performed, wherein multiple literature databases from 2018 and 2022 were searched. Prospective, randomised, controlled trials comparing outcomes after PCI with TiNOS vs. DES in any coronary artery disease (CAD) were searched. Clinical outcomes were meta-analytic pooled risk ratios (RR) of device-oriented Major Adverse Cardiac Events (MACE) and their components. The analysis stratified outcomes reported with ACS-only vs. ACS jointly with chronic coronary syndrome (CCS). (3) Results: Five RCTs were eligible, comprising 1855 patients with TiNOS vs. 1363 with DES at a 1-year follow-up. Three enrolled patients presented with ACS only and two with ACS or CCS. The latter accounted for most of the patients. The one-year pooled RRs in those three RCTs were as follows: MACE 0.93 [0.72, 1.20], recurrent myocardial infarction (MI) 0.48 [0.31, 0.73], cardiac death (CD) 0.66 [0.33, 1.31], clinically driven target lesion revascularization (TLR) 1.55 [1.10, 2.19], and stent thrombosis (ST) 0.35 [0.20, 0.64]. Those results were robust to a sensitivity analysis. The evidence certainty was high in MACE and moderate or low in the other endpoints. (4) Conclusions: TiNOS are a non-inferior and safe alternative to DES in patients with ACS.

(1) Background: Three antimicrobial absorbable sutures have different triclosan (TS) loads, triclosan release kinetics and hydrolysis times. This in vitro study aims to analyse and compare their antimicrobial pharmacodynamics. (2) Methods: Time-kill assays were performed with eight triclosan-susceptible microorganisms common in surgical site infections (SSIs) and a segment of each TS. Microbial concentrations were measured at T0, T4, T8 and T24 h. Similar non-triclosan sutures (NTS) were used as controls. Microbial concentrations were plotted and analysed with panel analysis. They were predicted over time with a double-exponential model and four parameters fitted to each TS × microorganism combination. (3) Results: The microbial concentration was associated with the triclosan presence, timeslot and microorganism. It was not associated with the suture material. All combinations shared a common pattern with an early steep concentration reduction from baseline to 4–8 h, followed by a concentration up to a 24-h plateau in most cases with a mild concentration increase. (4) Conclusions: Microorganisms seem to be predominantly killed by contact or near-contact killing with the suture rather than the triclosan concentration in the culture medium. No significant in vitro antimicrobial pharmacodynamic difference between the three TS is identified. Triclosan can reduce the suture microbial colonisation and SSI risk.

Randomised controlled clinical trials (RCTs) report a lower incidence rate of surgical site infections (SSIs) with triclosan sutures (TSs) compared with non-triclosan sutures (NTSs). Do triclosan sutures modify the microbial diversity of culture-confirmed SSIs (ccSSIs)? If so, this would support the association between TS antimicrobial activity and the SSI incidence rate. This prospective systematic literature review (PROSPERO CRD42019125099) was conducted according to PRISMA. RCTs that compared the incidence of SSIs with TSs and NTSs and reported microbial counts from SSI cultures per suture group were eligible. The microbial species were grouped by genus, and the association between genera and sutures was tested. The pooled relative risk (RR) of ccSSIs was also calculated. Twelve RCTs were eligible. No publication bias was identified. The microorganism count was 180 in 124 SSIs with TSs versus 246 in 199 SSIs with NTSs. No significant difference in microbial diversity was found, but statistical power was low for test results to support or challenge the association between the antimicrobial activity of TSs and the reduced rate of SSIs. The RR of the ccSSIs was significant and consistent with comprehensive meta-analyses. The certainty of the pooled RR was moderate.

Users of newly marketed drugs often differ from the patients included in randomized clinical trials, and from patients prescribed similar drugs. Cohorts of such users may be compared using propensity score adjustment, or similar user cohorts may be built using high-dimensional propensity score matching in large population databases. One such database is SNDS, the French nationwide claims and hospitalization database, which covers 99 % of the French population. It has yet been rarely used.To study the comparative effectiveness and safety in secondary coronary prevention of ticagrelor, compared to clopidogrel or prasugrel, we identified in SNDS patients who were dispensed any of the three antiplatelet agents of interest (± aspirin) within a month after discharge from hospital for acute coronary syndrome (ACS) and followed them one year for recurrence of ACS, stroke, acute bleeding, or death. High-dimensional propensity scores were developed to identify matched cohorts. Drug performances were also compared in the whole population using adjustment on the same parameters. Here we describe the database that was used, and the methods developed for the high-dimensional propensity score matching, resulting in standardized mean differences between the matched populations of less than 2 % for all of the 500+ variables included in the model. • This study was done in a newly available large-scale claims database, which may differ from other population databases, by it size and exhaustiveness • The methods elaborate on standard high-dimensional propensity scores as adapted to this claims database

(1) Background: Sutures with triclosan (TS) are used to reduce the risk of surgical site infections (SSI), but most clinical trials are inconclusive. The traceability of SSI risk to antimicrobial activity in operated tissues is needed. (2) Objectives: This study aimed to predict triclosan antistaphylococcal activity in operated tissues. (3) Methods: Three TS were exposed to static water for 30 days, and triclosan release was recorded. Polyglactin TS explanted from sheep seven days after cardiac surgery according to 3Rs provided ex vivo acceleration benchmarks. TS immersion up to 7 days in ethanol-water cosolvency and stirring simulated tissue implantation. Controls were 30-day immersion in static water. The release rate over time was measured and fitted to a predictive function. Antistaphylococcal activity and duration were measured by time-kill analysis with pre-immersed polyglactin TS. (4) Fifteen to 60-fold accelerated in vitro conditions reproduced the benchmarks. The rate prediction with double-exponential decay was validated. The antistaphylococcal activity was bactericidal, with TS pre-immersed for less than 12 h before then S. aureus began to grow. The residual triclosan level was more than 95% and played no detectable role. (5) Conclusions: Polyglactin, poliglecaprone, and polydioxanone TS share similar triclosan release functions with parametric differences. Polyglactin TS is antistaphylococcal in surgical conditions for 4 to 12 h.

Abstract Background Allergic rhinitis affects around one quarter of the Western European population. Prophylactic allergen immunotherapy may be useful to reduce the risk of acute symptomatic attacks (hayfever). A five-grass pollen extract sublingual immunotherapy (5GPE-SLIT) has been developed for the treatment of allergic rhinitis to grass pollen. The objective of this study was to describe real-world treatment patterns with 5GPE-SLIT in France with respect to the prescribing information. Methods This prospective cohort study was conducted by 90 community and hospital allergists. Adults and children (> 5 years old) starting a first treatment with 5GPE-SLIT prior to the 2015 pollen season were eligible. Data was collected at the inclusion visit and at the end of the pollen season. The primary outcome variable was compatibility of 5GPE-SLIT prescription with the prescribing information. This was determined with respect to four variables: (1) interval between 5GPE-SLIT initiation and onset of the pollen season ≥ 3 months, (2) age of patient ≥ 5 years, (3) intermittent symptoms or mild symptom severity (4) confirmatory diagnostic test. At study end, symptoms reported during the pollen season and any modifications to treatment or adverse events were documented. Results 280 adults and 203 children were enrolled. The prescribing information was respected for 82.5% of adults and 86.7% of children. A skin test was performed for all patients. 5GPE-SLIT was started 3–5 months before the pollen season for 85.3%. Treatment was discontinued before the start of the pollen season in 11.0% of patients overall, generally because of an adverse event (78.8% of discontinuations). The mean duration of treatment was 5.2 months in adults and 5.6 months in children. At the end of follow-up, symptoms during the pollen season were intermittent for 75.0% of adults and 85.7% of children, and severity was mild for 61.8 and 66.0% respectively. During 5GPE-SLIT, the following symptoms reported during the previous year were not reported again in > 50% of patients: nasal congestion, rhinorrhoea, repeated sneezing, conjunctivitis and nasal pruritus. Conclusions 5GPE-SLIT use was generally consistent with prescribing recommendations and was associated with an improvement of AR severity, with resolution of the principal AR symptoms in around half the patients treated. Trial registration EUPAS9358. Registered 13 May 2015. Not prospectively registered. http://www.encepp.eu/encepp/viewResource.htm?id=16229