Search

Background: The relation between α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and age-related macular degeneration (AMD) is unclear. European researchers reported that ≤40% of ALA can be present as trans forms. Objective: We aimed to evaluate the associations between intake of ALA and intermediate and advanced AMD. Design: Seventy-five thousand eight hundred eighty-nine women from the Nurses' Health Study and 38,961 men from Health Professionals Follow-Up Study were followed up from 1984 to 2012 and from 1986 to 2010, respectively. We assessed dietary intake by a validated food-frequency questionnaire at baseline and every 4 y thereafter. One thousand five hundred eighty-nine incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) were confirmed by medical record review. Results: The multivariable-adjusted HR for intermediate AMD comparing ALA intake at the top quintile to the bottom quintile was 1.28 (95% CI: 1.05, 1.56; P-trend = 0.01) in the analyses combining 2 cohorts. The HR in each cohort was in the positive direction but reached statistical significance only in the women. However, the positive association was apparent only in the pre-2002 era in each cohort and not afterward (P-time interaction = 0.003). ALA intake was not associated with advanced AMD in either time period. Using gas-liquid chromatography, we identified both cis ALA (mean ± SD: 0.13% ± 0.04%) and trans ALA isomers (0.05% ± 0.01%) in 395 erythrocyte samples collected in 1989-1990. In stepwise regression models, mayonnaise was the leading predictor of erythrocyte concentrations of cis ALA and one isomer of trans ALA. We also found trans ALA in mayonnaise samples. Conclusions: A high intake of ALA was associated with an increased risk of intermediate AMD before 2002 but not afterward. The period before 2002 coincides with the same time period when trans ALA was found in food and participants' blood; this finding deserves further study. [ABSTRACT FROM AUTHOR]

Large cohort studies examining trends in cancer-related suicide are lacking. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 4,870,410 patients diagnosed with cancer from 1975 to 2017 in the United States. Joinpoint regression was used to estimate the annual percent change (APC) and average annual percentage change (AAPC) of age-adjusted rates of suicide. In the past 40 years, we revealed a gradual increase in cancer-related suicide rates from 1975 to 1989, followed by a gradual decrease from 1989 to 2013, and a marked decrease from 2013 to 2017. These trends suggested the potential impact of advancements in psychosocial care for patients with cancer in contributing to the observed decrease in suicide rates., (© 2024. The Author(s).)

Background: Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation., Methods: We report the outcomes of BMT CTN 1502, a single-arm, phase 2 clinical trial done at academic bone marrow transplantation centres in the USA. Included patients were children and adults (75 years or younger) with severe aplastic anaemia that was refractory (fulfilment of severe aplastic anaemia disease criteria at least 3 months after initial immunosuppressive therapy) or relapsed (initial improvement of cytopenias after first-line immunosuppressive therapy but then a later return to fulfilment of severe aplastic anaemia disease criteria), adequate performance status (Eastern Cooperative Oncology Group score 0 or 1, Karnofsky or Lansky score ≥60%), and the presence of an eligible related haploidentical donor. The regimen used reduced-intensity conditioning (rabbit anti-thymocyte globulin 4·5 mg/kg in total, cyclophosphamide 14·5 mg/kg daily for 2 days, fludarabine 30 mg/m 2 daily for 5 days, total body irradiation 200 cGy in a single fraction), related HLA-haploidentical donors, and post-transplantation cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Additionally, for GVHD prophylaxis, mycophenolate mofetil was given orally at a dose of 15 mg/kg three times a day up to 1 g three times a day (maximum dose 3000 mg per day) from day 5 to day 35, and tacrolimus was given orally or intravenously from day 5 to day 180 as per institutional standards to maintain a serum concentration of 10-15 ng/mL. The primary endpoint was overall survival 1 year after bone marrow transplantation. All patients treated per protocol were analysed. This study is complete and is registered with ClinicalTrials.gov, NCT02918292., Findings: Between May 1, 2017, and Aug 30, 2020, 32 patients with relapsed or refractory severe aplastic anaemia were enrolled from 14 centres, and 31 underwent bone marrow transplantation. The median age was 24·9 years (IQR 10·4-51·3), and median follow-up was 24·3 months (IQR 12·1-29·2). Of the 31 patients who received a transplant, 19 (61%) were male and 12 (39%) female. 13 (42%) patients were site-reported as non-White, and 19 (61%) were from under-represented racial and ethnic groups; there were four (13%) patients who were Asian, seven (23%) Black, one (3%) Hawaiian/Pacific Islander, and one (3%) more than one race, with seven (23%) patients reporting Hispanic ethnicity. 24 (77%) of 31 patients were alive with engraftment at 1 year, and one (3%) patient alive with autologous recovery. The 1-year overall survival was 81% (95% CI 62-91). The most common grade 3-5 adverse events (seen in seven or more patients) included seven (23%) patients with abnormal liver tests, 15 (48%) patients with cardiovascular changes (including sinus tachycardia, heart failure, pericarditis), ten (32%) patients with gastrointestinal issues, seven (23%) patients with nutritional disorders, and eight (26%) patients with respiratory disorders. Six (19%) deaths, due to disease and unsuccessful bone marrow transplantation, were reported after transplantation., Interpretation: Haploidentical bone marrow transplantation using this approach results in excellent overall survival with minimal GVHD in patients who have not responded to immunosuppressive therapy, and can expand access to bone marrow transplantation across all populations. In clinical practice, this could now be considered a standard approach for salvage treatment of severe aplastic anaemia. Attention to obtaining high cell doses (>2·5 × 10 8 nucleated marrow cells per kg of recipient ideal bodyweight) from bone marrow harvests is crucial to the success of this approach., Funding: US National Heart, Lung, and Blood Institute and US National Cancer Institute., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD)., Methods: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS)., Results: Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037)., Conclusion: CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival., Competing Interests: Leo LuznikConsulting or Advisory Role: Gilead Sciences, Talaris Therapheutics, Precision BioSciences, Rubius Therapheutics, WindMiL TherapheuticsResearch Funding: Genentech, Amgen (I)Patents, Royalties, Other Intellectual Property: Patent holder WindMIL therapheuticsUncompensated Relationships: WindMIL therapheutics Marcelo C. PasquiniHonoraria: HonorariaConsulting or Advisory Role: Pfizer, Medigene (Inst), Amgen¸ Bristol Myers SquibbResearch Funding: Kite/Gilead (Inst), Novartis (Inst), Bristol Myers Squibb (Inst) Brent LoganConsulting or Advisory Role: Daiichi Sankyo, Enlivex Therapeutics Ltd, Gamida Cell Robert J. SoifferLeadership: Kiadis Pharma, Be the Match/NMDPConsulting or Advisory Role: Juno Therapeutics, Gilead Sciences, Rheos Medicines, Cugene, Jazz Pharmaceuticals, Precision Biosciences, Takeda, Jasper Therapeutics, Alexion PharmaceuticalsExpert Testimony: PfizerTravel, Accommodations, Expenses: Gilead Sciences Steven M. DevineThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Honoraria: Kiadis PharmaConsulting or Advisory Role: Bristol Myers SquibbResearch Funding: Orca Bio (Inst), Kiadis Pharma (Inst)Travel, Accommodations, Expenses: Orca Bio Sergio GiraltThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Honoraria: Celgene, Takeda, Amgen, Jazz Pharmaceuticals, SanofiConsulting or Advisory Role: Celgene, Takeda, Sanofi, Jazz Pharmaceuticals, Amgen, Janssen, Actinuum, Bristol Myers Squibb, Johnson & Johnson, PfizerResearch Funding: Celgene (Inst), Takeda, Miltenyi Biotec (Inst), Johnson & Johnson, Amgen, Actinuum, SanofiTravel, Accommodations, Expenses: Celgene, Sanofi, Amgen, Jazz Pharmaceuticals Helen E. HeslopStock and Other Ownership Interests: Marker Therapeutics, Allovir, Fresh Wind BiotechnologiesConsulting or Advisory Role: Gilead Sciences, Novartis, Kiadis Pharma, Tessa Therapeutics, Marker Therapeutics, PACT Pharma, Mesoblast, GlaxoSmithKline, Takara BioResearch Funding: Tessa Therapeutics (Inst) Mary M. HorowitzConsulting or Advisory Role: MedacResearch Funding: Biovitrum (Inst), Jazz Pharmaceuticals (Inst), Magenta Therapeutics (Inst), Novartis (Inst), Kite/Gilead (Inst), Actinium Pharmaceuticals (Inst), Amgen (Inst), Bluebird Bio (Inst), Bristol Myers Squibb (Inst), Chimerix (Inst), CSL Behring¸ Daiichi Sankyo (Inst), Gamida Cell (Inst), GlaxoSmithKline (Inst), Mesoblast (Inst), Miltenyi Biotec (Inst), Oncoimmune (Inst), Pfizer (Inst), Pharmacyclics (Inst), Regeneron (Inst), Sanofi (Inst), Seattle Genetics (Inst), Shire (Inst), Astellas Pharma, Xenikos (Inst) Mark R. LitzowConsulting or Advisory Role: Omeros, Jazz PharmaceuticalsResearch Funding: Amgen, Astellas Pharma, Actinium Pharmaceuticals, Pluristem Therapeutic, AbbVie/Genentech, Tolero Pharmaceuticals, AbbVieOther Relationship: Biosight Lori MufflyStock and Other Ownership Interests: Corvus PharmaceuticalsHonoraria: UpToDateConsulting or Advisory Role: Pfizer, Amgen, medexus, Jazz PharmaceuticalsSpeakers' Bureau: Adaptive BiotechnologiesResearch Funding: Shire, Adaptive Biotechnologies, Astellas Pharma, Jasper Therapeutics Eneida R. NemecekConsulting or Advisory Role: Medexus, Medac, Novartis, Atara Biotherapeutics Richard J. O'ReillyConsulting or Advisory Role: Atara BiotherapeuticsResearch Funding: Atara BiotherapeuticsPatents, Royalties, Other Intellectual Property: I have received royalties following licensure of the EBV-specific T-cell bank by Atara Biotherapeutics Johannes ScheteligHonoraria: Roche, AbbVie, Janssen, Bristol Myers Squibb/Sanofi, Gilead Sciences, AstraZenecaConsulting or Advisory Role: AstraZeneca, AbbVie, Janssen Sumithira VasuConsulting or Advisory Role: Omeros, Johnson and JohnsonResearch Funding: SanofiOpen Payments Link: https://openpaymentsdata.cms.gov/physician/725618 Vincent T. HoConsulting or Advisory Role: Jazz Pharmaceuticals, Janssen, Alexion Pharmaceuticals, OmerosResearch Funding: Jazz Pharmaceuticals Miguel-Angel PeralesStock and Other Ownership Interests: NexImmuneHonoraria: MorphoSysConsulting or Advisory Role: Incyte, Merck, Servier/Pfizer, NexImmune, Novartis, MolMed¸ Medigene, Takeda, Nektar, AbbVie, Cidara Therapeutics, Celgene, Kite/Gilead, Bristol Myers Squibb, Omeros, Vor BiopharmaResearch Funding: Incyte (Inst), Miltenyi Biotec (Inst), Novartis (Inst), Kite, a Gilead company (Inst), Nektar (Inst)No other potential conflicts of interest were reported.

Background and Objectives: The traditional open approach is still a common option for colectomy and the most common option chosen for rectal resections for cancer. Randomized trials and large database studies have reported the merits of the minimally invasive approach, while studies comparing laparoscopic and robotic options have reported inconsistent results., Methods: This study was designed to compare open, laparoscopic, and robotic colorectal surgery outcomes in protocol-driven regional and national databases. Logistic and multiple linear regression analyses were used to compare standard 30-day colorectal outcomes in the Michigan Surgical Quality Collaborative (MSQC) and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases. The primary outcome was overall complications., Results: A total of 10,054 MSQC patients (open 37.5%, laparoscopic 48.8%, and robotic 13.6%) and 80,535 ACS-NSQIP patients (open 25.0%, laparoscopic 67.1%, and robotic 7.9%) met inclusion criteria. Overall complications and surgical site infections were significantly favorable for the laparoscopic and robotic approaches compared with the open approach. Anastomotic leaks were significantly fewer for the laparoscopic and robotic approaches compared with the open approach in ACS-NSQIP, while there was no significant difference between robotic and open approaches in MSQC. Laparoscopic complications were significantly less than robotic complications in MSQC but significantly more in ACS-NSQIP. Laparoscopic 30-day mortality was significantly less than for the robotic approach in MSQC, but there was no difference in ACS-NSQIP., Conclusion: Minimally invasive colorectal surgery is associated with fewer complications and has several other outcomes advantages compared with the traditional open approach. Individual complication comparisons vary between databases, and caution should be exercised when interpreting results in context., Competing Interests: Conflicts of Interest: All authors declare no conflict of interest regarding the publication of this article.

Objective: The minimally invasive approach to colorectal surgery is still underused. Only 50% to 60% of colectomies and 10% to 20% of rectal resections for cancer are performed laparoscopically. The increasing adoption of the robotic platform for colorectal surgery warrants re-evaluation of minimally invasive surgery (MIS) training techniques. Although considering lessons learned from past laparoscopic training, a standardized national robotic training program for colon and rectal surgery residents was developed and implemented in 2011. The objective of this study was to assess the effect of this program on the usage of MIS in practice following residency training., Design: An internet-based 18 question survey was sent to all colon and rectal surgeons who graduated from ACGME-approved colon and rectal surgery residencies from 2013 to 2016. The survey questions were designed to determine MIS practice patterns for young colon and rectal surgeons after residency training for those who participated in the standardized national robotics training course when compared to those who did not participate. Grouped bar charts with error bars are presented along with summary statistics to offer a descriptive overview of training experiences by cohort., Setting/participants: This study is a survey of colon and rectal surgeons who completed colon and rectal surgery residencies to include all 52 programs across the United States., Results: The overall survey response rate was 37.2% (109 of 293). Most (79.8%) of the colon and rectal surgery resident respondents participated in the formal robotic training course. The average respondent reported that 84% of colectomy cases and 74.8% of rectal resections done after residency training by all respondents were by the MIS approach. The laparoscopic approach was most prevalent for colectomies for both course participants (laparoscopic 55.1%, hand assisted lap 14.5%, and robotic 15.7%) and nonparticipants (laparoscopic 53.8%, hand assisted lap 12.3%, and robotic 15.9%). For rectal resections, the robotic approach was the preferred option for course participants (laparoscopic 24.5%, hand assist lap 14.0%, and robotic 39.2%) whereas laparoscopic and open approaches were used more often by nonparticipants (laparoscopic 36.8%, hand assist lap 8.0%, robotic 26.8%, and open 28.4%). Barriers to robotic implementation included lack of robotic mentors, inadequate robotic assistance, and the preference for the laparoscopic approach., Conclusion: The usage of MIS by young recently fellowship-trained colorectal surgeons is higher than previously reported. The proportion of rectal cases done robotically is higher compared to colon cases and with an apparent decrease in open rather than laparoscopic surgery, suggesting selective usage of robotic surgery for more challenging cases in the pelvis. Methods to more effectively increase the usage of minimally invasive approaches in colorectal surgery warrant further evaluation., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Autologous haemopoietic stem-cell transplantation (HSCT) improves survival in patients with multiple myeloma, but disease progression remains an issue. Allogeneic HSCT might reduce disease progression, but can be associated with high treatment-related mortality. Thus, we aimed to assess effectiveness of allogeneic HSCT with non-myeloablative conditioning after autologous HSCT compared with tandem autologous HSCT., Methods: In our phase 3 biological assignment trial, we enrolled patients with multiple myeloma attending 37 transplant centres in the USA. Patients (<70 years old) with adequate organ function who had completed at least three cycles of systemic antimyeloma therapy within the past 10 months were eligible for inclusion. We assigned patients to receive an autologous HSCT followed by an allogeneic HSCT (auto-allo group) or tandem autologous HSCTs (auto-auto group) on the basis of the availability of an HLA-matched sibling donor. Patients in the auto-auto group subsequently underwent a random allocation (1:1) to maintenance therapy (thalidomide plus dexamethasone) or observation. To avoid enrolment bias, we classified patients as standard risk or high risk on the basis of cytogenetics and β2-microglobulin concentrations. We used the Kaplan-Meier method to estimate differences in 3-year progression-free survival (PFS; primary endpoint) between patients with standard-risk disease in the auto-allo group and the best results from the auto-auto group (maintenance, observation, or pooled). This study is registered with ClinicalTrials.gov, number NCT00075829., Findings: Between Dec 17, 2003, and March 30, 2007, we enrolled 710 patients, of whom 625 had standard-risk disease and received an autologous HSCT. 156 (83%) of 189 patients with standard-risk disease in the auto-allo group and 366 (84%) of 436 in the auto-auto group received a second transplant. 219 patients in the auto-auto group were randomly assigned to observation and 217 to receive maintenance treatment, of whom 168 (77%) completed this treatment. PFS and overall survival did not differ between maintenance and observation groups and pooled data were used. Kaplan-Meier estimates of 3-year PFS were 43% (95% CI 36-51) in the auto-allo group and 46% (42-51) in the auto-auto group (p=0·671); overall survival also did not differ at 3 years (77% [95% CI 72-84] vs 80% [77-84]; p=0·191). Within 3 years, 87 (46%) of 189 patients in the auto-allo group had grade 3-5 adverse events as did 185 (42%) of 436 patients in the auto-auto group. The adverse events that differed most between groups were hyperbilirubinaemia (21 [11%] patients in the auto-allo group vs 14 [3%] in the auto-auto group) and peripheral neuropathy (11 [6%] in the auto-allo group vs 52 [12%] in the auto-auto group)., Interpretation: Non-myeloablative allogeneic HSCT after autologous HSCT is not more effective than tandem autologous HSCT for patients with standard-risk multiple myeloma. Further enhancement of the graft versus myeloma effect and reduction in transplant-related mortality are needed to improve the allogeneic HSCT approach., Funding: US National Heart, Lung, and Blood Institute and the National Cancer Institute., (Copyright © 2011 Elsevier Ltd. All rights reserved.)