Several functional parameters from baseline (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography have been proposed as promising biomarkers of treatment efficacy in diffuse large B-cell lymphoma (DLBCL). We tested their ability to predict outcome in 2 cohorts of DLBCL patients receiving conventional immunochemotherapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP] regimen), either every 14 (R-CHOP14) or 21 days (R-CHOP21). Baseline PET analysis was performed in 141 patients with DLBCL treated with R-CHOP14 in the prospective SAKK38/07 study (NCT00544219) of the Swiss Group for Clinical Cancer Research (testing set). Reproducibility was examined in a validation set of 113 patients treated with R-CHOP21. In the SAKK38/07 cohort, progression-free survival (PFS) at 5 years was 83% for patients with low metabolic tumor volume (MTV) and 59% for those with high MTV (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-7.0; P = .0005), whereas overall survival (OS) was 91% and 64%, respectively (HR, 4.4; 95% CI, 1.9-10; P = .0001). MTV was the most powerful predictor of outcome also in the validation set. Elevated metabolic heterogeneity (MH) significantly predicted poorer outcomes in the subgroups of patients with elevated MTV. A model integrating MTV and MH identified high-risk patients with shorter PFS (testing set: HR, 5.6; 95% CI, 1.8-17; P < .0001; validation set: HR, 5.6; 95% CI, 1.7-18; P = .0002) and shorter OS (testing set: HR, 9.5; 95% CI, 1.7-52; P < .0001; validation set: HR, 7.6; 95% CI, 2.0-28; P = .0003). This finding was confirmed by an unsupervised regression tree analysis indicating that prognostic models based on MTV and MH may allow early identification of refractory patients who might benefit from treatment intensification. This trial was registered at www.clinicaltrials.gov as #NCT00544219.

Key Points Question Is there a role for platinum-based treatment in molecularly selected patients with advanced prostate cancer? Findings In a case series of 508 patients, platinum-based therapy was associated with antitumor activity, especially among patients with known DNA repair gene aberrations. In patients with DNA repair gene aberrations, nearly half had a decrease in prostate-specific antigen levels of at least 50% and experienced soft tissue responses. Meaning In patients with prostate cancer and DNA repair gene aberrations, platinum-based therapy may be considered a treatment option.

Swallowtail butterflies (Papilionidae) are among the most spectacular and well‐known Lepidoptera in the European fauna, but their systematics is not fully elucidated. A notable case is that of Iphiclides feisthamelii which, after more than 180 years since description, still has a debated status, being often considered as a subspecies of Iphiclides podalirius. To elucidate the relationship between the two taxa and the evolutionary processes that led to their separation, we combine mitochondrial and nuclear DNA (mtDNA and nDNA) data, Wolbachia screening, genitalia morphology and wing UV reflectance. Our results show that the two taxa clearly differ in male and female genital morphology, male wing UV reflectance and nDNA. Two Wolbachia strains were found to widely infect the studied samples, apparently explaining the phylogeographic pattern displayed by mtDNA. The available data point towards a historical Wolbachia infection that spread from I. podalirius to I. feisthamelii and produced a mitochondrial introgression. Currently, a new Wolbachia strain is spreading across mainland populations of I. podalirius, mediating once more a mitochondrial genetic sweep, which has already infected and introgressed I. feisthamelii populations in south‐eastern France. We conclude that, given the marked differences in morphology and nDNA between the two taxa, and the apparent restriction of hybridization to a narrow contact area where non‐hybrid specimens are common, the taxon feisthamelii should be considered as a separate species. Within this species, two well‐differentiated nDNA lineages that represent European and Maghrebian populations are documented, here proposed as subspecies. The case of, presumably, two consecutive Wolbachia‐mediated mitochondrial introgression events, further supports the view that infection by this endosymbiont may be frequently related to mito‐nuclear discordance in insects.

Aim Continents harbour unique faunas, and only a small percentage of species naturally inhabit more than a single continent. This pattern is most evident in the insects, a morphologically small and extremely diverse group. Nevertheless, 12 species of ants have traditionally been recognized as native to both North America and Eurasia, the Holarctic region. Since intercontinental dispersal is presumably rare in ants, allopatric speciation in the absence of gene flow can be expected over evolutionary time. Here, we reassess the existence of Holarctic ant species and reconstruct their biogeographical history. Location The Holarctic. Taxon All known ant species with purportedly Holarctic distributions. Methods We reconstructed the phylogenetic relationships, biogeographical history and reassessed the taxonomic status of all known ants with Holarctic distributions using genetic data based on one mitochondrial and three nuclear genes and an ancestral area reconstruction of 310 specimens and 73 species (the 12 Holarctic species plus outgroup taxa). Results Contrary to the currently accepted hypothesis, only three ant species have Holarctic native ranges, while six taxa separate into distinct Palearctic and Nearctic species. Four species are shown to be recent introductions from Europe to North America by human activity, one of which was thought to be native. Genetic diversity is considerably higher within the North American than within European species as currently defined. Main conclusions The Formicidae have repeatedly dispersed through Beringia, during and after land bridge formation, and in both directions between the Palearctic and Nearctic regions. However, only three cold‐tolerant species crossed the Bering Strait in relatively recent time. Our results highlight the potential existence of many unknown Nearctic ant taxa. Reliance on an evolutionarily labile morphological character, erect hairs, seems to have obscured species delimitation in these ant taxa. Based on our investigation, the typical time for speciation in allopatry for ants is 2–5 Ma.

Myelodysplastic syndromes (MDSs) represent a heterogeneous group of hematological stem cell disorders with an increasing burden on health care systems. Evidence-based MDS guidelines and recommendations (G/Rs) are published but do not necessarily translate into better quality of care if adherence is not maintained in daily clinical practice. Guideline-based indicators (GBIs) are measurable elements for the standardized assessment of quality of care and, thus far, have not been developed for adult MDS patients. To this end, we screened relevant G/Rs published between 1999 and 2018 and aggregated all available information as candidate GBIs into a formalized handbook as the basis for the subsequent consensus rating procedure. An international multidisciplinary expert panel group (EPG) of acknowledged MDS experts (n = 17), health professionals (n = 7), and patient advocates (n = 5) was appointed. The EPG feedback rates for the first and second round were 82% (23 of 28) and 96% (26 of 27), respectively. A final set of 29 GBIs for the 3 domains of diagnosis (n = 14), therapy (n = 8), and provider/infrastructural characteristics (n = 7) achieved the predefined agreement score for selection (>70%). We identified shortcomings in standardization of patient-reported outcomes, toxicity, and geriatric assessments that need to be optimized in the future. Our GBIs represent the first comprehensive consensus on measurable elements addressing best practice performance, outcomes, and structural resources. They can be used as a standardized instrument with the goal of assessing, comparing, and fostering good quality of care within clinical development cycles in the daily care of adult MDS patients.