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- Khoury, J. D., et al.
(författare)
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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
- 2022
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36, s. 1703-1719
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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| 8. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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- Hoban, Sean, et al.
(författare)
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Global Commitments to Conserving and Monitoring Genetic Diversity Are Now Necessary and Feasible
- 2021
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 71:9, s. 964-976
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Tidskriftsartikel (refereegranskat)abstract
- Global conservation policy and action have largely neglected protecting and monitoring genetic diversity-one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species' adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity.
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- Chhabra, Saurabh, et al.
(författare)
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Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:21, s. 2922-2936
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.
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- Purrington, Kristen S., et al.
(författare)
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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
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Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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| 19. |
- Rogozińska, Ewelina, et al.
(författare)
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Effects of antenatal diet and physical activity on maternal and fetal outcomes : Individual patient data meta-analysis and health economic evaluation
- 2017
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Ingår i: Health Technology Assessment. - : National Institute for Health Research. - 1366-5278 .- 2046-4924. ; 21:41
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes. Objectives: To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions. Data sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search). Review methods: Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions. Results: Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI-0.92 to-0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate-0.10 kg, 95% CI-0.14 to-0.06 kg) and multiparity (summary estimate-0.73 kg, 95% CI-1.24 to-0.23 kg). Limitations: The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies. Conclusion: Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes. Future work: The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation. Study registration: This study is registered as PROSPERO CRD42013003804.
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| 20. |
- Terracciano, A, et al.
(författare)
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National character does not reflect mean personality trait levels in 49 cultures
- 2005
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 310:5745, s. 96-100
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Tidskriftsartikel (refereegranskat)abstract
- Most people hold beliefs about personality characteristics typical of members of their own and others' cultures. These perceptions of national character may be generalizations from personal experience, stereotypes with a "kernel of truth," or inaccurate stereotypes. We obtained national character ratings of 3989 people from 49 cultures and compared them with the average personality scores of culture members assessed by observer ratings and self-reports. National character ratings were reliable but did not converge with assessed traits. Perceptions of national character thus appear to be unfounded stereotypes that may serve the function of maintaining a national identity.
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- Zabriskie, Matthew S., et al.
(författare)
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BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
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Tidskriftsartikel (refereegranskat)abstract
- Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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- Akouri, Randa R., et al.
(författare)
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First live birth after uterus transplantation in the Middle East
- 2020
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Ingår i: Middle East Fertility Society Journal. - : Springer Science and Business Media LLC. - 1110-5690 .- 2090-3251. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The first live birth after uterus transplantation took place in Sweden in 2014. It was the first ever cure for absolute uterine factor infertility. We report the surgery, assisted reproduction, and pregnancy behind the first live birth after uterus transplantation in the Middle East, North Africa, and Turkey (MENAT) region. A 24-year old woman with congenital absence of the uterus underwent transplantation of the uterus donated by her 50-year-old multiparous mother. In vitro fertilization was performed to cryopreserve embryos. Both graft retrieval and transplantation were performed by laparotomy. Donor surgery included isolation of the uterus, together with major uterine arteries and veins on segments of the internal iliac vessels bilaterally, the round ligaments, and the sacrouterine ligaments, as well as with bladder peritoneum. Recipient surgery included preparation of the vaginal vault, end-to-side anastomosis to the external iliac arteries and veins on each side, and then fixation of the uterus. Results One in vitro fertilization cycle prior to transplantation resulted in 11 cryopreserved embryos. Surgical time of the donor was 608 min, and blood loss was 900 mL. Cold ischemia time was 85 min. Recipient surgical time was 363 min, and blood loss was 700 mL. Anastomosis time was 105 min. Hospital stay was 7 days for both patients. Ten months after the transplantation, one previously cryopreserved blastocyst was transferred which resulted in viable pregnancy, which proceeded normally (except for one episode of minor vaginal bleeding in the 1st trimester) until cesarean section at 35 + 1 weeks due to premature contractions and shortened cervix. A healthy girl (Apgar 9-10-10) weighing 2620 g was born in January 2020, and her development has been normal during the first 6 months. Conclusions This is the first report of a healthy live birth after uterus transplantation in the MENAT region. We hope that this will motivate further progress and additional clinical trials in this area in the Middle East Region, where the first uterus transplantation attempt ever, however unsuccessful, was performed already three decades ago.
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| 25. |
- Callander, Margarita, 1964-, et al.
(författare)
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Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis
- 2007
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:4, s. 441-445
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Tidskriftsartikel (refereegranskat)abstract
- We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic.
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| 29. |
- Deol, Abhinav, et al.
(författare)
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Does FLT3 Mutation Impact Survival After Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia? : A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis
- 2016
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 122:19, s. 3005-3014
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P = .04; relative risk, 1.60 [95% CI, 1.15-2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P = .20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.
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| 30. |
- El-Khoury, Antoine E, et al.
(författare)
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Moderate exercise at energy balance does not affect 24-h leucine oxidation or nitrogen retention in healthy men
- 1997
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Ingår i: American Journal of Physiology. - 0002-9513 .- 2163-5773. ; 273:2, s. E394-E407
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Tidskriftsartikel (refereegranskat)abstract
- Short-term metabolic experiments have revealed that physical exercise increases the oxidation of leucine, which has been interpreted to indicate an increased requirement for dietary protein in physically active subjects. Because it may be inaccurate to extrapolate measurements of amino acid oxidation made over a few hours to the entire day, we have carried out a continuous 24-h intravenous [1-13C]leucine/[15N]urea tracer study in eight healthy adult men. Their diet supplied 1 g protein.kg-1.day-1, and exercise (mean maximal O2 consumption 46%) was for 90 min during the 12-h fast and 12-h fed periods of the day. Subjects were adapted to the diet and exercise regimen for 6 days. Then, on day 7, they were dressed in the University of Uppsala energy metabolic unit's direct calorimeter suit, were connected to an open-hood indirect calorimeter, and received the tracers. Exercise increased leucine oxidation by approximately 50 and 30% over preexercise rates for fast and fed periods, respectively. This increase amounted to approximately 4-7% of daily leucine oxidation. Subjects remained in body leucine equilibrium (balance -4.6 +/- 10.5 mg.kg-1.day-1; -3.6 +/- 8.3% of intake; P = not significant from zero balance). Therefore, moderate exercise did not cause a significant deterioration in leucine homeostasis at a protein intake of 1 g.kg-1.day-1. These findings underscore the importance of carrying out precise, continuous, 24-h measurements of whole body leucine kinetics; this model should be of value in studies concerning the quantitative interactions among physical exercise, energy/protein metabolism, and diet in humans.
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| 31. |
- Eriksson, Kimmo, et al.
(författare)
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Perceptions of the appropriate response to norm violation in 57 societies
- 2021
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
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| 33. |
- Goldberg, Stuart L., et al.
(författare)
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First-line treatment selection and early monitoring patterns in chronic phase-chronic myeloid leukemia in routine clinical practice : SIMPLICITY
- 2017
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 92:11, s. 1214-1223
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Tidskriftsartikel (refereegranskat)abstract
- Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted.
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| 38. |
- Jacquot, F., et al.
(författare)
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Lysophophatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3
- 2022
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Ingår i: Pain. - : International Association for the Study of Pain. - 0304-3959 .- 1872-6623. ; 163:10, s. 1999-2013
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatic diseases are often associated to debilitating chronic pain, which remains difficult to treat and requires new therapeutic strategies. We had previously identified lysophosphatidylcholine (LPC) in the synovial fluids from few patients and shown its effect as a positive modulator of acid-sensing ion channel 3 (ASIC3) able to induce acute cutaneous pain in rodents. However, the possible involvement of LPC in chronic joint pain remained completely unknown. Here, we show, from 2 independent cohorts of patients with painful rheumatic diseases, that the synovial fluid levels of LPC are significantly elevated, especially the LPC16:0 species, compared with postmortem control subjects. Moreover, LPC16:0 levels correlated with pain outcomes in a cohort of osteoarthritis patients. However, LPC16:0 do not appear to be the hallmark of a particular joint disease because similar levels are found in the synovial fluids of a second cohort of patients with various rheumatic diseases. The mechanism of action was next explored by developing a pathology-derived rodent model. Intra-articular injections of LPC16:0 is a triggering factor of chronic joint pain in both male and female mice, ultimately leading to persistent pain and anxiety-like behaviors. All these effects are dependent on ASIC3 channels, which drive sufficient peripheral inputs to generate spinal sensitization processes. This study brings evidences from mouse and human supporting a role for LPC16:0 via ASIC3 channels in chronic pain arising from joints, with potential implications for pain management in osteoarthritis and possibly across other rheumatic diseases.
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| 39. |
- Keasar, Chen, et al.
(författare)
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An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.
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| 40. |
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| 41. |
- Khoury, L, et al.
(författare)
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Management of Thoracic and Lumbar Spine Fractures: Is MRI Necessary in Patients without Neurological Deficits?
- 2019
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Ingår i: The American surgeon. - : SAGE Publications. - 1555-9823 .- 0003-1348. ; 85:3, s. 306-311
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Tidskriftsartikel (refereegranskat)abstract
- MRI after a CTscan for thoracolumbar spine (TLS) trauma has become commonplace because of the concerns for detection of posterior ligamentous complex injuries in the absence of substantial scientific evidence to support its use. We hypothesized that MRI scans were not necessary in the clinical management of TLS fractures. A prospective study was conducted at our Level I trauma center. A total of 39 neurologically intact patients with TLS fracture on CT were enrolled. The patients’ CT scan and neurological examination were reviewed by a senior neurosurgeon, who determined clinical management based on these data. Assessment was repeated after an MRI of the spine was performed, and a second clinical plan was devised. The two treatment schemes were then compared. MRI resulted in a change in clinical management in 15 per cent of patients. Ten per cent of patients changed from requiring a brace to no brace and merely observation alone. In no patient planned for nonoperative care was surgery deemed necessary after completion of MRI. Among five patients with initial plans for operative intervention, two avoided surgery after the MRI. MRI has little impact on the management of patients with CT-proven thoracic and lumbar spine fractures. Only when surgery is planned based on CT studies does an MRI seem to assist with determining optimal care.
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- Parker, W. A. E., et al.
(författare)
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Prevalence of microspirometry-defined chronic obstructive pulmonary disease in two European cohorts of patients with significant smoking history hospitalised for acute myocardial infarction
- 2023
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 78:Suppl. 4, s. A66-A66
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Smoking is a major risk factor for both chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI). Systemic inflammation also contributes to both diseases and has been suggested as a potential target for intervention. Prevalence of COPD in those with a significant smoking history hospitalised for MI has not been well-characterised. We sought to obtain an accurate estimate of COPD burden in this group and characterise the population.Methods: Two consecutive cohorts of patients hospitalised for MI with a smoking history of ≥10 pack-years were recruited in Sweden and the United Kingdom (UK). Baseline characteristics were recorded, including treatment with inhaled corticosteroids (ICS) and eosinophil count in blood. Microspirometry was performed using the Vitalograph COPD-6 device and symptom burden assessed using the COPD Assessment Test (CAT). The primary outcome was the prevalence of a preliminary diagnosis of clinically-significant COPD, here defined as a ratio of forced expiratory volume in 1 and 6 seconds (FEV1/FEV6) <0.7 and with FEV1 <80% of predicted value.Results: In the UK cohort, 216 participants with MI (26% female, median age 60 (IQR 53–67) years, smoking history 32 (23–45) pack-years) were recruited. The proportion with any COPD was 36%. Clinically-significant COPD was found in 30 participants (13.9%, 95% CI 9.5–19.2). Of these, 43% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 14.4 ± 9.3), 80% had high symptom burden (CAT score >10) and 23% were receiving ICS. The Swedish cohort included 302 participants with MI (24% female, median age 68 (IQR 61–76) years, 26 (15–38) pack years), and clinically-significant COPD was found in 52 (17.2%; 12.9–21.5). In these 52 participants, 17% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 12.9 ± 7.2, 63% had CAT score ≥10 and 15% had treatment with ICS.Conclusions: The prevalence of preliminary diagnosis of clinically-significant COPD in patients with a ≥10 pack-year smoking history hospitalised for MI is similar between two European cohorts and under-recognised. Further work is warranted to determine whether identification and treatment of COPD improves clinical outcomes following MI.
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