BACKGROUND: Recent randomized trials demonstrated the beneficial effect of endovascular therapy in patients with low Alberta Stroke Program Early CT Score. Despite large follow-up infarct volumes, a significantly increased rate of good functional outcomes was observed, challenging the role of infarct volume as a predictive imaging marker. This analysis evaluates the extent to which the effects of endovascular thrombectomy on functional outcomes are explained by (1) follow-up infarct volume and (2) early neurological status in patients with stroke with low Alberta Stroke Program Early CT Score. METHODS: TENSION (Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window) was a randomized trial conducted from February 2018 to January 2023 across 41 stroke centers. Two hundred fifty-three patients with ischemic stroke due to anterior circulation large vessel occlusion and Alberta Stroke Program Early CT Score of 3 to 5 were randomized to endovascular thrombectomy plus medical treatment or medical treatment alone. All patients with the availability of relevant data points were included in this secondary as-treated analysis. The primary outcome was the 90-day modified Rankin Scale score. Confounder-adjusted mediation analysis was performed to quantify the proportion of the treatment effect on a 90-day modified Rankin Scale score explained by (1) 24-hour follow-up infarct volume and (2) 24-hour National Institutes of Health Stroke Scale scores. RESULTS: One hundred eighty-eight patients were included; thereof, 87 (46%) were female patients. Median age was 72 (interquartile range, 63-79) years. The endovascular thrombectomy cohort had a 20.5 (95% CI, 8.3-33.7) percentage points higher probability of achieving independent ambulation (modified Rankin Scale, 0-3) and a 24.2 (95% CI, 13.4-35.8) percentage points lower mortality at 90 days compared with medical treatment alone. The reduction in 24-hour follow-up infarct volume explained 30% of the treatment effect on functional outcomes, while the 24-hour National Institutes of Health Stroke Scale score explained 61%. CONCLUSIONS: In patients with low Alberta Stroke Program Early CT Score, infarct volume demonstrated limited explanatory power for functional outcomes compared with the early neurological status, which may more effectively reflect factors such as the involvement of specific brain regions, disruption of structural networks, and selective neuronal loss.
- MeSH
- Endovascular Procedures methods MeSH
- Ischemic Stroke * surgery diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Thrombectomy * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
OBJECTIVES: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification. MATERIALS AND METHODS: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up. Seventy cases were reviewed by 42 pulmonary pathologists first according to the WHO classification and after tutorial according to a modified classification. A third round was conducted based on feedback from 41 peers of previous rounds. Additionally, orthogonal biomarker analysis was performed. RESULTS: In the first two rounds, 42 pathologists from 13 countries assessed all 70 cases, while 36 pathologists evaluated 41 non-unanimous cases in the third round. Kappa values for invasiveness increased in rounds 1, 2, and 3 to 0.27, 0.45 and 0.62, respectively. In contrast to low variation in total tumor size measurements (6 %), a marked increase in invasive tumor size variation was observed (42 %), which was associated with high uncertainty. In the third round 10 cases were non-invasive, all without recurrence. The modified classification showed in the 3rd round marked reduction of the variation in pT staging compared to the current WHO classification. Proliferation rate, tumor mutational burden, and transcriptomic profiles supported the distinction between invasive cases and non-invasive cases of the modified classification. CONCLUSION: The modified classification demonstrates essentially higher reproducibility compared to the current WHO classification in NMA. The modified classification proves valuable in identifying low-risk lesions that are entirely non-invasive, and is supported by biomarker analysis.
- MeSH
- Adenocarcinoma of Lung * pathology metabolism classification diagnosis MeSH
- Adult MeSH
- Neoplasm Invasiveness * MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * metabolism MeSH
- Lung Neoplasms * pathology classification diagnosis MeSH
- Follow-Up Studies MeSH
- Reproducibility of Results MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging * MeSH
- Case-Control Studies MeSH
- World Health Organization * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
People differ in their general tendency to endorse conspiracy theories (that is, conspiracy mentality). Previous research yielded inconsistent findings on the relationship between conspiracy mentality and political orientation, showing a greater conspiracy mentality either among the political right (a linear relation) or amongst both the left and right extremes (a curvilinear relation). We revisited this relationship across two studies spanning 26 countries (combined N = 104,253) and found overall evidence for both linear and quadratic relations, albeit small and heterogeneous across countries. We also observed stronger support for conspiracy mentality among voters of opposition parties (that is, those deprived of political control). Nonetheless, the quadratic effect of political orientation remained significant when adjusting for political control deprivation. We conclude that conspiracy mentality is associated with extreme left- and especially extreme right-wing beliefs, and that this non-linear relation may be strengthened by, but is not reducible to, deprivation of political control.
- Publication type
- Journal Article MeSH
Interpersonal touch behavior differs across cultures, yet no study to date has systematically tested for cultural variation in affective touch, nor examined the factors that might account for this variability. Here, over 14,000 individuals from 45 countries were asked whether they embraced, stroked, kissed, or hugged their partner, friends, and youngest child during the week preceding the study. We then examined a range of hypothesized individual-level factors (sex, age, parasitic history, conservatism, religiosity, and preferred interpersonal distance) and cultural-level factors (regional temperature, parasite stress, regional conservatism, collectivism, and religiosity) in predicting these affective-touching behaviors. Our results indicate that affective touch was most prevalent in relationships with partners and children, and its diversity was relatively higher in warmer, less conservative, and religious countries, and among younger, female, and liberal people. This research allows for a broad and integrated view of the bases of cross-cultural variability in affective touch.
The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
- MeSH
- Survival Analysis MeSH
- Aniline Compounds therapeutic use MeSH
- Fusion Proteins, bcr-abl antagonists & inhibitors genetics metabolism MeSH
- Quinolines therapeutic use MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis drug therapy genetics mortality MeSH
- Dasatinib therapeutic use MeSH
- Gene Expression MeSH
- Imatinib Mesylate therapeutic use MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Clinical Decision-Making MeSH
- Consensus Development Conferences as Topic MeSH
- Quality of Life MeSH
- Humans MeSH
- Disease Management MeSH
- Monitoring, Physiologic MeSH
- Life Expectancy trends MeSH
- Nitriles therapeutic use MeSH
- Antineoplastic Agents therapeutic use MeSH
- Pyrimidines therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.
- MeSH
- Influenza, Human epidemiology mortality MeSH
- Length of Stay statistics & numerical data MeSH
- Hospitalization statistics & numerical data MeSH
- Immunocompromised Host immunology MeSH
- Cohort Studies MeSH
- Coinfection epidemiology mortality MeSH
- Critical Illness epidemiology mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Hospital Mortality trends MeSH
- Prospective Studies MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Propensity Score MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 109 /l and peripheral blood plasma cell count ≥20 × 109 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2-3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.
- MeSH
- Autografts MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Leukemia, Plasma Cell mortality pathology therapy MeSH
- Disease-Free Survival MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Stem Cell Transplantation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Multicenter Study MeSH
The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575-580, 2016. © 2016 Wiley Periodicals, Inc.
- MeSH
- Survival Analysis MeSH
- Chromosome Aberrations MeSH
- Adult MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Multiple Myeloma complications mortality pathology therapy MeSH
- Central Nervous System Neoplasms diagnosis mortality secondary therapy MeSH
- Prognosis MeSH
- Antineoplastic Agents therapeutic use MeSH
- Radiotherapy MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region. METHODS: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls. RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 × 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 0.92-1.21), indicating that this association was specific to the EBV-positive subgroup (Phet < P = 10(-8)). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histologic subtype of cHL. CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL. IMPACT: This expands the number of genetic variants that are associated with cHL and provides additional evidence for a critical and specific role of EBV in the etiology of this disease.
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Major Histocompatibility Complex genetics MeSH
- Hodgkin Disease epidemiology genetics pathology virology MeSH
- Epstein-Barr Virus Infections epidemiology genetics pathology virology MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Chromosomes, Human, Pair 6 * MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Netherlands epidemiology MeSH
- Scandinavian and Nordic Countries epidemiology MeSH
In recent decades, naturally growing mosses have been used successfully as biomonitors of atmospheric deposition of heavy metals and nitrogen. Since 1990, the European moss survey has been repeated at five-yearly intervals. In 2010, the lowest concentrations of metals and nitrogen in mosses were generally found in northern Europe, whereas the highest concentrations were observed in (south-)eastern Europe for metals and the central belt for nitrogen. Averaged across Europe, since 1990, the median concentration in mosses has declined the most for lead (77%), followed by vanadium (55%), cadmium (51%), chromium (43%), zinc (34%), nickel (33%), iron (27%), arsenic (21%, since 1995), mercury (14%, since 1995) and copper (11%). Between 2005 and 2010, the decline ranged from 6% for copper to 36% for lead; for nitrogen the decline was 5%. Despite the Europe-wide decline, no changes or increases have been observed between 2005 and 2010 in some (regions of) countries.
- MeSH
- Bryophyta chemistry MeSH
- Nitrogen analysis MeSH
- Cadmium analysis MeSH
- Metals MeSH
- Air Pollutants analysis MeSH
- Environmental Monitoring * MeSH
- Nickel MeSH
- Mercury MeSH
- Metals, Heavy analysis MeSH
- Iron MeSH
- Air Pollution statistics & numerical data MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
