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Diabetes Care Sep 2023To study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes...
OBJECTIVE
To study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes (T2D), in a large-scale prospective cohort.
RESEARCH DESIGN AND METHODS
The analyses included 105,588 participants from the web-based NutriNet-Santé study (France, 2009-2022; mean age 42.5 ± 14.6 years, 79.2% women). Repeated 24-h dietary records, including brands and commercial names of industrial products, merged with qualitative and quantitative food additive composition data, enabled artificial sweetener intakes to be accurately assessed from all dietary sources. Associations between artificial sweeteners (total, aspartame, acesulfame potassium [K], and sucralose) and T2D were investigated using Cox proportional hazard models adjusted for potential confounders, including weight variation during follow-up.
RESULTS
During a median follow-up of 9.1 years (946,650 person-years, 972 incident T2D), compared with nonconsumers, higher consumers of artificial sweeteners (i.e., above the sex-specific medians of 16.4 mg/day in men and 18.5 mg/day in women) had higher risks of developing T2D (hazard ratio [HR] 1.69; 95% CI 1.45-1.97; P-trend <0.001). Positive associations were also observed for individual artificial sweeteners: aspartame (HR 1.63 [95% CI 1.38-1.93], P-trend <0.001), acesulfame-K (HR 1.70 [1.42-2.04], P-trend <0.001), and sucralose (HR 1.34 [1.07-1.69], P-trend = 0.013).
CONCLUSIONS
Potential for reverse causality cannot be eliminated; however, many sensitivity analyses were computed to limit this and other potential biases. These findings of positive associations between artificial sweetener intakes and increased T2D risk strengthen the evidence that these additives may not be safe sugar alternatives. This study provides important insights in the context of on-going reevaluation of artificial sweeteners by health authorities worldwide.
Topics: Male; Humans; Female; Adult; Middle Aged; Sweetening Agents; Diabetes Mellitus, Type 2; Aspartame; Prospective Studies; Diet
PubMed: 37490630
DOI: 10.2337/dc23-0206 -
Blood Feb 2024Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma...
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.
Topics: Humans; Follow-Up Studies; Neoplasm Recurrence, Local; Biological Products; Immunotherapy, Adoptive; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Antigens, CD19
PubMed: 37879047
DOI: 10.1182/blood.2023021243 -
Ugeskrift For Laeger Dec 2023This is a case report of a four-year-old boy who suffered a forearm fracture managed with closed reduction and casting for six weeks. Postoperatively, the patient showed...
This is a case report of a four-year-old boy who suffered a forearm fracture managed with closed reduction and casting for six weeks. Postoperatively, the patient showed symptoms of median nerve affection which was misinterpreted as neuropraxia. Ultrasonography of the forearm revealed that the median nerve was trapped in the radius fracture site. The patient underwent a second operation with neurolysis and nerve grafting. This case report highlights the use of ultrasonography in the diagnostics of nerve entrapment neuropathy.
Topics: Male; Child; Humans; Child, Preschool; Forearm; Ulna Fractures; Median Neuropathy; Radius Fractures; Nerve Compression Syndromes
PubMed: 38105734
DOI: No ID Found -
JAMA Oncology Nov 2023Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in...
IMPORTANCE
Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1-selected tumors.
OBJECTIVE
To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors.
DESIGN, SETTING, AND PARTICIPANTS
The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022.
INTERVENTIONS
Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity.
MAIN OUTCOMES AND MEASURES
The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables.
RESULTS
Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non-small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months).
CONCLUSIONS AND RELEVANCE
In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy-naive metastatic NSCLC or EC.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02794571.
Topics: Humans; Female; Middle Aged; Male; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antineoplastic Agents; Esophageal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Receptors, Immunologic
PubMed: 37768658
DOI: 10.1001/jamaoncol.2023.3867 -
Cancers Jun 2023Intensified systemic therapy in metastatic renal cell carcinoma (mRCC) has led to improved patient outcomes. Patients commonly require local control of one or a few... (Review)
Review
Intensified systemic therapy in metastatic renal cell carcinoma (mRCC) has led to improved patient outcomes. Patients commonly require local control of one or a few metastases. The aim was to evaluate metastasis-directed ablative therapies in extracranial mRCC. Two databases and one registry were searched, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach, for all prospective and matched-pair case-control mRCC studies of radiofrequency ablation (RFA), cryotherapy, microwave ablation (MWA), and stereotactic body radiotherapy (SBRT). Eighteen studies were identified. Fourteen investigated SBRT in 424 patients. Four thermal ablation studies were identified: two cryotherapy (56 patients) and two RFA studies (90 patients). The median participant number was 30 (range 12-69). The combined median follow-up was 17.3 months (range 8-52). Four SBRT studies reported local control (LC) at 12 months, median 84.4% (range 82.5-93). Seven studies (six SBRT and one cryotherapy) reported an LC rate of median 87% (79-100%). Median overall survival (OS) was reported in eight studies (five SBRT, two cryotherapy, and one RFA) with a median of 22.7 months (range 6.7-not reached). Median progression-free survival was reported in seven studies (five SBRT, one cryotherapy, and one RFA); the median was 9.3 months (range 3.0-22.7 months). Grade ≥ 3 toxicity ranged from 1.7% to 10%. SBRT has excellent local control outcomes and acceptable toxicity. Only four eligible thermal ablative studies were identified and could not be compared with SBRT. Translationally rich definitive studies are warranted.
PubMed: 37444565
DOI: 10.3390/cancers15133455 -
Journal of the American Heart... Sep 2023Background Evidence is limited regarding the associations of prenatal and childhood per- and polyfluoroalkyl substance (PFAS) exposures with blood pressure (BP)...
Prenatal and Childhood Per- and Polyfluoroalkyl Substance (PFAS) Exposures and Blood Pressure Trajectories From Birth to Late Adolescence in a Prospective US Prebirth Cohort.
Background Evidence is limited regarding the associations of prenatal and childhood per- and polyfluoroalkyl substance (PFAS) exposures with blood pressure (BP) trajectories in children. Methods and Results Participants are from Project Viva, a prospective prebirth cohort in eastern Massachusetts. We measured PFAS in early-pregnancy maternal (median, 9.6 weeks) and midchildhood (median, 7.7 years) plasma samples. We conducted standardized BP measurements at 6 research visits: birth, infancy (median, 6.3 months), early childhood (median, 3.2 years), midchildhood (median, 7.7 years), early adolescence (median, 12.9 years), and late adolescence (median, 17.5 years). We used linear regression to examine associations of individual PFASs with BP at each visit, linear spline mixed-effects regression to model BP trajectories, and a mixture approach to estimate PFAS exposure burden. We included 9036 BP measures from 1506 participants. We observed associations between particular individual prenatal PFASs and child BP at specific time points, for example, prenatal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) with higher systolic BP at birth; prenatal perfluorooctane sulfonate (PFOS) and EtFOSAA with lower diastolic BP in infancy; and prenatal PFOS, perfluorooctanoate (PFOA), and EtFOSAA with higher systolic BP at midchildhood. No prenatal or childhood PFAS was consistently associated with BP across all visits. Diastolic BP trajectories from 0 to 20 years differed slightly by prenatal PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) ( values 0.01-0.09). Diastolic BP trajectories from 6 to 20 years differed slightly by midchildhood PFHxS and MeFOSAA (-values 0.03-0.08). Prenatal or childhood PFAS mixture burden scores were not associated with BP. Conclusions We found associations of prenatal and childhood PFAS exposures with BP at specific time points between birth and late adolescence but no consistent associations across all time points or PFAS types.
Topics: Infant, Newborn; Child; Female; Pregnancy; Humans; Adolescent; Child, Preschool; Blood Pressure; Prospective Studies; Fluorocarbons; Hypotension; Alkanesulfonates
PubMed: 37642023
DOI: 10.1161/JAHA.123.030760 -
Tidsskrift For Den Norske Laegeforening... Oct 2023Since 2009, patients with a rapidly progressing lung disease have been given a higher priority on the waiting list for a lung transplant. The purpose of our study was to...
BACKGROUND
Since 2009, patients with a rapidly progressing lung disease have been given a higher priority on the waiting list for a lung transplant. The purpose of our study was to examine diagnosis distribution, waiting list times, mortality and survival for patients on the waiting list in the period 1999-2020.
MATERIAL AND METHOD
We conducted a descriptive, retrospective study of patients on the waiting list for a lung transplant in the periods 1999-2008 and 2009-2020.
RESULTS
A total of 557 lung transplants were performed: 185 in 1999-2008 (median of 17.5 per year) and 372 in 2009-2020 (median of 32.5 per year). In the periods 1999-2008 and 2009-2020, the proportion of patients with chronic obstructive pulmonary disease (COPD)/emphysema was 67 % and 49 %, respectively. The corresponding figures for pulmonary fibrosis were 13 % and 23 %, and for cystic fibrosis 5 % and 11 %. Waiting list mortality was 27 % in 1999-2008 and 16 % in 2009-2020. Correspondingly for the two periods, waiting list mortality for patients with pulmonary fibrosis was 45 % and 22 %, and for cystic fibrosis 41 % and 2 %. Waiting times were shorter for all diagnoses in the period after the change in priority and longest for patients with COPD/emphysema (median of 381 days). Median survival after lung transplantation during the study period was ten years.
INTERPRETATION
For patients with pulmonary fibrosis and cystic fibrosis, the change in transplant priority in 2009 may have played a role in reducing waiting list mortality.
Topics: Humans; Cystic Fibrosis; Pulmonary Fibrosis; Retrospective Studies; Lung Transplantation; Pulmonary Disease, Chronic Obstructive; Emphysema; Waiting Lists
PubMed: 37830971
DOI: 10.4045/tidsskr.22.0775