Evaluation of a pneumonia multiplex PCR panel for detection of bacterial respiratory tract pathogens from serial specimens collected from hospitalized COVID-19 patients

European Journal of Clinical Microbiology & Infectious Diseases - We investigated the concordance between the Unyvero Hospitalized Pneumonia (HPN) application and quantitative culture for...     

Effectiveness,safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.     

Perinatal and familial risk factors for soft tissue sarcomas in childhood through young adulthood: A population-based assessment in 4 million live births

Perinatal factors have been associated with soft tissue sarcomas (STS) in case-control studies. However, (i) the contributions of factors including fetal growth remain unknown, ( ii ) these factors have not been examined in cohort studies and (iii) few assessments have evaluated risk in specific STS subtypes. We sought to identify the role of perinatal and familial factors on the risk of STS in a large population-based birth cohort. We identified 4,023,436 individuals in the Swedish Birth Registry born during 1973–2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including fetal growth, gestational age, and presence of a congenital malformation. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for associations between perinatal factors and STS overall, as well as by common subtypes. There were 673 individuals diagnosed with STS in 77.5 million person-years of follow-up. Having a congenital malformation was associated with STS (IRR = 1.70, 95% CI: 1.23–2.35). This association was stronger (IRR = 2.90, 95% CI: 1.25–6.71) in recent years (2000–2012). Low fetal growth was also associated with STS during the same time period (IRR = 1.86, 95% CI: 1.05–3.29). Being born preterm was associated with rhabdomyosarcoma (IRR = 1.74, 95% CI: 1.08–2.79). In our cohort study, those with congenital malformations and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways and genetic factors influencing the risk of STS.     

Deep sequencing detects human papillomavirus (HPV) in cervical cancers negative for HPV by PCR

Background Human papillomavirus (HPV) is a necessary cause of cervical cancer, although some invasive cervical cancers may test negative by HPV PCR. We previously requested all invasive cervical cancers in Sweden during 10 years and subjected them to PCR. We also optimised methods for deep sequencing of formalin-fixed paraffin-embedded samples.Methods Using Novaseq 6000, we simultaneously sequenced total DNA and cDNA from 392 HPV PCR-negative cervical cancers. Non-human reads were queried against all known HPVs. The complete database now contains PCR and/or deep sequencing data on 2850 invasive cervical cancers.Results HPV sequences were detected in 169/392 of HPV PCR-negative cervical cancers. Overall, 30 different HPV types were detected, but only 5 types were present in proportions above 3% of cancers. More than 92% of tumours were HPV-positive in PCR and/or sequencing (95% confidence interval: 91.1–93.1%). Exploring possible reasons for failure to previously detect HPV suggest that more sensitive type-specific PCRs for HPV 31, 33, 45 and 73 targeting retained regions of HPV would have detected most of these (117/392).Conclusions Unbiased deep sequencing provides comprehensive data on HPV types in cervical cancers and appears to be an important tool for quality assurance of HPV screening.Subject terms: Infectious-disease diagnostics, Viral infection, Cervical cancer     

Reproduction patterns among classical Hodgkin lymphoma survivors treated with BEACOPP and ABVD in Sweden,Denmark and Norway—A population-based matched cohort study

Childbirth rates in classical Hodgkin lymphoma (cHL) survivors have historically been reduced compared to the general population. Understanding if contemporary treatment protocols are associated with reduced fertility is crucial as treatment guidelines shift toward more liberal use of intensive chemotherapy. We identified 2834 individuals aged 18-40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital diagnosed 1995-2018, who were linked to national medical birth registers. Cox regression adjusted for stage, performance status, year, and age at diagnosis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) contrasting time to first childbirth by treatment groups (ABVD, 2-4 BEACOPP, 6-8 BEACOPP) up to 10 years after diagnosis. Overall, 74.8% of patients were treated with ABVD, 3.1% with 2-4 BEACOPP and 11.2% with 6-8 BEACOPP. Adjusted HRs comparing childbirth rates in individuals treated with 6-8 BEACOPP, and 2-4 BEACOPP to ABVD were 0.53 (CI: 0.36-0.77) and 0.33 (CI: 0.12-0.91) for males, and 0.91 (CI: 0.61-1.34) and 0.38 (CI: 0.12-1.21) for females. Cumulative incidence of childbirths after 10 years was 19.8% (CI: 14.5%-27.0%) for males and 34.3% (CI: 25.8%-45.6%) for females treated with 6-8 BEACOPP. Proportions of children born after assisted reproductive technique (ART) treatments were 77.4% (CI: 60.2-88.6%) for males following 6-8 BEACOPP, and <11% for females. Among ABVD treated patients the corresponding proportions were 12.2% (CI: 8.5%-17.3%) and 10.6% (CI: 7.4%-14.9%). BEACOPP treatment is associated with decreased childbirth rates compared to ABVD in male, but not female, cHL patients, despite widespread access to ART in the Nordics.     

A multitaxa assessment of the effectiveness of agri-environmental schemes for biodiversity management

Agri-environmental schemes (AES) aim to restore biodiversity and biodiversity-mediated ecosystem services in landscapes impoverished by modern agriculture. However, a systematic, empirical evaluation of different AES types across multiple taxa and functional groups is missing. Within one orthogonal design, we studied sown flowering AES types with different temporal continuity, size, and landscape context and used calcareous grasslands as seminatural reference habitat. We measured species richness of 12 taxonomic groups (vascular plants, cicadas, orthopterans, bees, butterflies, moths, hoverflies, flower visiting beetles, parasitoid wasps, carabid beetles, staphylinid beetles, and birds) representing 5 trophic levels. A total of 54,955 specimens were identified using traditional taxonomic methods, and bulk arthropod samples were identified through DNA metabarcoding, resulting in a total of 1,077 and 2,110 taxa, respectively. Species richness of most taxonomic groups, as well as multidiversity and richness of pollinators, increased with temporal continuity of AES types. Some groups responded to size and landscape context, but multidiversity and richness of pollinators and natural enemies were not affected. AES flowering fields supported different species assemblages than calcareous grasslands, but assemblages became more similar to those in seminatural grasslands with increasing temporal continuity. Our results indicate that AES flowering fields and seminatural grasslands function synergistically. Flowering fields support biodiversity even when they are relatively small and in landscapes with few remaining seminatural habitats. We therefore recommend a network of smaller, temporally continuous AES flowering fields of different ages, combined with permanent seminatural grasslands, to maximize benefits for biodiversity conservation and ecosystem service delivery in agricultural landscapes.

Human societies are facing a worldwide loss of biodiversity with alarming declines of insect diversity in temperate agricultural landscapes (1, 2). This loss of biodiversity is jeopardizing agricultural production as important ecosystem services ensuring crop yields are directly driven by biodiversity (3). Biodiversity, however, requires suitable habitats for species to persist, forage, nest, reproduce, and hibernate (4, 5). This challenge has been recognized and agri-environmental schemes (AES) have been introduced in the European Union and other regions to reverse biodiversity declines, to restore functional diversity, and to harness the benefits of ecosystem services, like pollination and pest control, in agricultural landscapes (6–8).An important component of AES to fulfill these goals is the establishing of habitats that provide limiting resources, such as food and shelter for a broad range of organisms. Typically, farmers are financially compensated on a per area basis, but the effectiveness of schemes is often unclear. Thus, compensations might not direct farmers’ decisions among different AES to the ecologically most meaningful ones (7). A variety of different habitats are created as AES, ranging from hedgerows to sown flower strips or flowering fields, with the latter being widely used due to their flexible applicability and public appreciation (4). Recent assessments, however, found that overall, European AES are not fulfilling their goals (6, 9). Particularly, the value of AES for securing biodiversity is under debate (10, 11). Beneficial effects previously reported focused on single taxonomic or trophic levels or ecosystem services and varied among study designs, taxa, or services assessed (12–14). Conclusive multitaxa approaches assessing potential services and disservices in one design are missing (8). Furthermore, it is unclear how different properties of AES habitats (e.g., their temporal continuity or size) and varying landscape context affect biodiversity across multiple taxonomic groups.Temporal continuity is an important factor affecting biodiversity. Higher temporal continuity increases heterogeneity within a habitat and creates niches for more species (15, 16). Temporal continuity also enables weak dispersers and higher tropic levels to colonize a habitat, with the latter being dependent on established populations of lower trophic levels (15). In AES habitats, the influence and the effects of temporal continuity have so far been neglected. Newly established flowering fields were found to be more attractive to pollinators than older flowering fields, but pollination services in adjacent fields peak 2 y after initial sowing (14, 17). Older AES habitats could potentially also benefit rare and endangered species with specific habitat requirements, if species assemblages in AES habitats change toward those in permanent species-rich seminatural grasslands with time or increased temporal continuity (18).Apart from temporal continuity, size might be an important predictor for the conservation value of AES habitats. Increasing habitat size leads to an increased species richness as it is accompanied with the establishment of larger, more stable populations and allows higher trophic levels to persist (19–21). It is unclear whether biodiversity in a landscape benefits more from few large habitats or a network of many small habitats (22, 23). Relationships between size and species richness might therefore be essential for the planning and strategic placement of AES habitats.Source habitats for biodiversity are needed in agricultural landscapes to build up local populations in newly established AES habitats from regional species pools (24). Seminatural habitats embedded in agricultural landscapes have been shown to support farmland diversity (25, 26), and thus AES habitats in complex landscapes with high proportions of seminatural habitats potentially host the highest diversity.Here, we investigate the effects of AES differing in temporal continuity, size, and surrounding landscape context over several years on multiple taxonomic groups within one study design. Different types of flowering fields are commonly established by farmers as part of AES to provide additional flower resources. These fields are sown with seed mixtures adapted to local soil properties and taken from regional species pools. After a certain timespan, often varying from 1 to 10 y, flowering fields are returned to crop production. The studied flowering fields differed in temporal continuity from: 1) Newly sown on arable land, over 2) refreshed (i.e., flower fields resown after 5 y) to 3) continuous, 6-y-old flowering fields. Species-rich calcareous grasslands were used as permanent control (Fig. 1 and Table 1). Calcareous grasslands are seminatural biodiversity hotspots in Europe and are preserved by low intensive mowing or grazing (27). We investigated species richness in these 4 AES types across 12 taxonomic groups belonging to 5 trophic levels, including pollinators (bees, butterflies, moths, flower visiting beetles, and hoverflies) and natural enemies (parasitoid wasps, carabid beetles, staphylinid beetles, and birds) as providers of important ecosystem services (3). Species were identified by classic taxonomic techniques (vascular plants, orthopterans, bees, butterflies, moths, flower visiting beetles, carabid beetles, staphylinid beetles, and birds) and DNA metabarcoding (cicadas, hoverflies, and parasitoid wasps). Repeated recordings of a subset of four taxonomic groups (plants, orthopterans, bees, and carabid beetles) within 2 y were performed to clarify whether short-term succession changed assemblages in newly established flowering fields toward those in seminatural calcareous grasslands. Apart from analyses for each taxonomic group, we performed a multidiversity analysis by calculating a diversity index across all taxa, pollinators, and natural enemies (28). Our study aims to judge which types of AES fulfill the goal of restoring biodiversity and ecosystem services in agricultural landscapes best, and should therefore be fostered. Such data are urgently needed to build the scientific basis for a successful transition of European Union and global policies to biodiversity-friendly and sustainable crop production.Open in a separate windowFig. 1.Study design on the landscape and site level. Biodiversity across 12 different taxonomic levels (from top to bottom: Vascular plants, orthopterans, cicadas, bees, butterflies, moths, flower visiting beetles, hoverflies, parasitoid wasps, carabid beetles, staphylinid beetles, birds) was recorded using a variety of classic methods (pan traps, pitfall traps, transect walks, light traps combined with taxonomic identification) as well as metabarcoding analyses (using samples collected with Malaise traps). The different types of flowering fields and calcareous grasslands were located along a gradient of temporal continuity (Table 1). All AES types covered independent gradients of seminatural habitat in the surrounding landscape and habitat size (purple, AES; yellow, arable land; light green, seminatural habitat; dark green, forest; gray, urban). Repeated recordings over 2 y were performed for vascular plants, orthopterans, bees, and carabid beetles to assess whether succession shifted assemblages in flowering fields toward those in seminatural calcareous grasslands.Table 1.Differences in temporal continuity

The Danish National Register of assisted reproductive technology: content and research potentials

European Journal of Epidemiology - The Danish National Register of assisted reproductive technology (ART) was initially established in 1994. The register comprises complete information on all ART...