The DIVE/DPV registries: evolution of empagliflozin use in clinical practice in Germany.

INTRODUCTION: Empagliflozin reduced morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) in clinical trials. A registry study was undertaken to describe evolution of patient characteristics and assess the real-world effectiveness/safety of empagliflozin. RESEARCH DESIGN AND METHODS: Data from the Diabetes Patienten Verlaufsdokumentation (DPV)/Diabetes Versorgungsevaluation (DIVE) registries on 9571 adults with T2DM (registered in 2014-2019) receiving empagliflozin were used. Patients were grouped according to the following: early users (group 1; n=505) received empagliflozin before the EMPA-REG OUTCOME study publication (mid-September 2015); intermediate users (group 2; n=2961) started empagliflozin after the EMPA-REG OUTCOME publication but before the European Medicines Agency label change (from mid-September 2015 to mid-January 2017); and late users (group 3; n=6105) started empagliflozin after mid-January 2017. Data on clinical and treatment characteristics were collected. RESULTS: Over time, the proportion of recipients aged <65 years decreased (71.1% vs 54.4% among early and late adopters), male patients increased (from 50.9% to 66.5%), body mass index (mean±SD) decreased (from 35.5±6.7 to 32.7±6.6 kg/m2), proportion with cardiovascular morbidities increased (from 20.4% to 26.4%), and mean estimated glomerular filtration rate decreased (from 83.2±19.5 to 78.5±21.1 mL/min/1.73 m2) (all p<0.001). Patients increasingly received empagliflozin in combination with metformin (60.8% vs 68.6% of early and late adopters; p<0.001), glucagon-like peptide-1 (GLP-1) agonists (11.0 vs 14.1%; p<0.001) or insulin (34.3% vs 49.9%; p<0.001). Empagliflozin was generally added to existing antidiabetic regimens. Six months after empagliflozin initiation, the mean glycated hemoglobin (HbA1c) decreased by 0.4%, the proportion of patients with HbA1c <6.5% increased (19.2% vs 12.8%), and the mean fasting plasma glucose decreased (155.8±49.7 vs 168.0±55.1 mg/dL) (all p<0.001). No significant changes in rates of severe hypoglycemia and no cases of diabetic ketoacidosis were seen. CONCLUSIONS: Over time, empagliflozin is being prescribed to a broader patient range in routine practice, is usually added to existing antidiabetic regimens, and is increasingly used in combination with metformin, GLP-1 agonists and/or insulin. Empagliflozin had a beneficial effect on glycemic control, with no increase in hypoglycemia.

Reproductive isolation due to prezygotic isolation and postzygotic cytoplasmic incompatibility in parasitoid wasps.

The reproductive barriers that prevent gene flow between closely related species are a major topic in evolutionary research. Insect clades with parasitoid lifestyle are among the most species-rich insects and new species are constantly described, indicating that speciation occurs frequently in this group. However, there are only very few studies on speciation in parasitoids. We studied reproductive barriers in two lineages of Lariophagus distinguendus (Chalcidoidea: Hymenoptera), a parasitoid wasp of pest beetle larvae that occur in human environments. One of the two lineages occurs in households preferably attacking larvae of the drugstore beetle Stegobium paniceum ("DB-lineage"), the other in grain stores with larvae of the granary weevil Sitophilus granarius as main host ("GW-lineage"). Between two populations of the DB-lineage, we identified slight sexual isolation as intraspecific barrier. Between populations from both lineages, we found almost complete sexual isolation caused by female mate choice, and postzygotic isolation, which is partially caused by cytoplasmic incompatibility induced by so far undescribed endosymbionts which are not Wolbachia or Cardinium. Because separation between the two lineages is almost complete, they should be considered as separate species according to the biological species concept. This demonstrates that cryptic species within parasitoid Hymenoptera also occur in Central Europe in close contact to humans.

Sexy Mouth Odour? Male Oral Gland Pheromone in the Grain Beetle Parasitoid Lariophagus distinguendus (Förster) (Hymenoptera: Pteromalidae).

Throughout the animal kingdom, sexual pheromones are used for the attraction of mates and as courtship signals but also enable sexual isolation between species. In the parasitic wasp Lariophagus distinguendus, male courtship behaviour consisting of wing fanning, antennal stroking of the female antenna, and head nodding stimulates female receptivity leading to copulation. Recently L. distinguendus was reported to consist of two different lineages, which are sexually isolated because males fail to elicit receptivity in foreign females. It is unclear, however, which part of the courtship behaviour triggers female receptivity and therefore could be a mechanism causing sexual isolation. Here we show that in L. distinguendus a nonvolatile male oral pheromone is essential to release the female receptivity signal. In contrast, male wing fanning and antennal contact play a minor role. Additionally, the composition of the oral pheromone depends on the developmental host and females learn the composition upon emergence from the host substrate. These results will enable more detailed work on oral sexual pheromones to answer the question of how they are involved in the speciation process of L. distinguendus and other parasitoid species, for a better understanding of the huge biodiversity in this group.

Does early learning drive ecological divergence during speciation processes in parasitoid wasps?

Central to the concept of ecological speciation is the evolution of ecotypes, i.e. groups of individuals occupying different ecological niches. However, the mechanisms behind the first step of separation, the switch of individuals into new niches, are unclear. One long-standing hypothesis, which was proposed for insects but never tested, is that early learning causes new ecological preferences, leading to a switch into a new niche within one generation. Here, we show that a host switch occurred within a parasitoid wasp, which is associated with the ability for early learning and the splitting into separate lineages during speciation. Lariophagus distinguendus consists of two genetically distinct lineages, most likely representing different species. One attacks drugstore beetle larvae (Stegobium paniceum (L.)), which were probably the ancestral host of both lineages. The drugstore beetle lineage has an innate host preference that cannot be altered by experience. In contrast, the second lineage is found on Sitophilus weevils as hosts and changes its preference by early learning. We conclude that a host switch has occurred in the ancestor of the second lineage, which must have been enabled by early learning. Because early learning is widespread in insects, it might have facilitated ecological divergence and associated speciation in this hyperdiverse group.

Frequency of bacteremia after linear EUS of the upper GI tract with and without FNA.

BACKGROUND: Few data are available concerning the frequency of bacteremia after diagnostic EUS or EUS-guided FNA. This study was undertaken to provide these data and to determine whether present guidelines for prophylactic administration of antibiotics to prevent endocarditis during upper endoscopy are applicable to EUS and EUS-guided FNA. METHODS: A total of 100 patients who were to undergo diagnostic EUS of the upper-GI tract and 50 who were to have upper-GI EUS-guided FNA were enrolled in this prospective study. Blood cultures were obtained before and within 5 minutes after the conclusion of the procedure. In case of bacterial growth, patients were observed for at least 3 days for signs of infection. RESULTS: After diagnostic EUS, significant bacteremia was found in two patients with esophageal carcinoma (2%: 95% CI[0%, 4.8%]) and after EUS-guided FNA in two patients (4%: 95% CI[0%, 9.6%]). The difference was not statistically significant. None of these patients developed clinical signs of infection. Risk factors predisposing to bacteremia could not be identified. CONCLUSION: The frequency of bacteremia after EUS, with and without FNA, is within the range of that for diagnostic upper endoscopy. Therefore, the same recommendations for prophylactic administration of antibiotics to prevent endocarditis may be applied in patients undergoing EUS and EUS-guided FNA. The role of esophageal cancer as a predisposing factor to EUS-associated infection remains uncertain.