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Experimental and Clinical... Dec 2023This editorial focuses on William W. Stoops time as editor of Stoops ends his time with gratitude for all who have contributed to the journal's success over the past...
This editorial focuses on William W. Stoops time as editor of Stoops ends his time with gratitude for all who have contributed to the journal's success over the past years, pride for what they have accomplished, and excitement for the journal's future. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Psychopharmacology; Emotions
PubMed: 38127504
DOI: 10.1037/pha0000696 -
Annals of Surgical Oncology Apr 2024Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it...
BACKGROUND
Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy.
PATIENTS AND METHODS
A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion.
RESULTS
Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS.
CONCLUSIONS
Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy.
Topics: Humans; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Induction Chemotherapy; Retrospective Studies; Fluorouracil; Leucovorin; Netherlands
PubMed: 38105377
DOI: 10.1245/s10434-023-14650-6 -
Applied Ergonomics Apr 2024This study quantified sex-specific biomechanical adaptations to fatigue in asymmetric lifting. Twenty-one females and fifteen males performed a prolonged asymmetric...
This study quantified sex-specific biomechanical adaptations to fatigue in asymmetric lifting. Twenty-one females and fifteen males performed a prolonged asymmetric lifting protocol while upper body, trunk and pelvis kinematics were collected. Features of movement identified with principal component analysis, and peak joint angular velocities and moments were calculated. Sex-specific kinematic adaptations to fatigue included females adopting a 'stoop-like' lifting strategy to a greater extent than males. Additionally, females exhibited higher vertical elbow positions during load rotation, moved their body toward the destination for load deposit, and did not reduce peak right shoulder flexion velocities, in contrast to male participants. Females also had greater low back and shoulder peak normalized joint moments. When fatigued, females adopted an asymmetric lifting strategy that minimized metabolic demand as supported by smaller decreases in maximum voluntary contractions. However, females' fatigue-related adaptations increased biomechanical exposures associated with injury risk.
Topics: Female; Humans; Male; Biomechanical Phenomena; Elbow; Lifting; Muscle Fatigue
PubMed: 38101162
DOI: 10.1016/j.apergo.2023.104203 -
Annals of Surgical Oncology Apr 2024
ASO Author Reflections: Nationwide Experience on Locally Advanced Pancreatic Cancer Surgery After Induction Chemotherapy in the Netherlands: A Stepping Stone for the PREOPANC-4 Trial.
Topics: Humans; Induction Chemotherapy; Neoadjuvant Therapy; Netherlands; Pancreas; Pancreatectomy; Pancreatic Hormones; Pancreatic Neoplasms; Clinical Trials as Topic
PubMed: 38093164
DOI: 10.1245/s10434-023-14704-9 -
Journal of Physical Therapy Science Dec 2023[Purpose] To present the dramatic improvement in posture, radiographic parameters and the alleviation of neck and severe shoulder pain related to shoulder injury...
Alleviation of shoulder injury related to vaccine administration (SIRVA) pain and disability following COVID-19 vaccine with chiropractic biophysics (CBP) methods: a case report and long-term follow-up with global implications.
[Purpose] To present the dramatic improvement in posture, radiographic parameters and the alleviation of neck and severe shoulder pain related to shoulder injury associated with vaccine administration (SIRVA) after a COVID-19 injection with a shoulder mobility and posture rehabilitation program. [Participant and Methods] A middle-aged male presented complaining of severe left shoulder pain evolving since receiving a COVID-19 vaccination. The pain was severe and throbbed into the neck. Posture analysis showed a chronic stooped posture with forward head posture and thoracic hyperkyphosis. Treatment included 42 sessions of Chiropractic Biophysics technique and a shoulder rehabilitation program using three-dimensional vibration. [Results] At 4-months, the patient reported no neck or shoulder pain. There was a 60% decrease in neck disability. The forward head decreased 34 mm, thoracic hyperkyphosis decreased 13°, and T1-T12 forward lean decreased 73 mm, among other radiographic parameters. Re-assessment after 26-months showed maintenance of the treatment induced posture/x-ray corrections and shoulder pain relief. [Conclusion] This case demonstrates immediate and long-term improvement in a patient suffering from COVID-19 vaccine SIRVA, concomitant with neck pain and disability as well as significant radiographic postural/spinal deformity. These conditions all improved and were maintained at a 2 year follow-up without further treatment.
PubMed: 38075507
DOI: 10.1589/jpts.35.831 -
Annals of Surgery Dec 2023To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.
OBJECTIVE
To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.
SUMMARY BACKGROUND DATA
Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.
METHODS
Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed.
RESULTS
Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%).
CONCLUSION
This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.
PubMed: 38073575
DOI: 10.1097/SLA.0000000000006174 -
Science Advances Dec 2023Clonotypic αβ T cell responses to cargoes presented by major histocompatibility complex (MHC), MR1, or CD1 proteins underpin adaptive immunity. Those responses are...
Clonotypic αβ T cell responses to cargoes presented by major histocompatibility complex (MHC), MR1, or CD1 proteins underpin adaptive immunity. Those responses are mostly mediated by complementarity-determining region 3 motifs created by quasi-random T cell receptor (TCR) gene rearrangements, with diversity being highest for TCRγδ. Nonetheless, TCRγδ also displays nonclonotypic innate responsiveness following engagement of germline-encoded Vγ-specific residues by butyrophilin (BTN) or BTN-like (BTNL) proteins that uniquely mediate γδ T cell subset selection. We now report that nonclonotypic TCR engagement likewise induces distinct phenotypes in TCRαβ cells. Specifically, antibodies to germline-encoded human TCRVβ motifs consistently activated naïve or memory T cells toward core states distinct from those induced by anti-CD3 or superantigens and from others commonly reported. Those states combined selective proliferation and effector function with activation-induced inhibitory receptors and memory differentiation. Thus, nonclonotypic TCRVβ targeting broadens our perspectives on human T cell response modes and might offer ways to induce clinically beneficial phenotypes in defined T cell subsets.
Topics: Humans; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocyte Subsets; Butyrophilins; Phenotype; Immunotherapy
PubMed: 38055824
DOI: 10.1126/sciadv.adj6174 -
Nature Reviews. Gastroenterology &... Feb 2024Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered... (Review)
Review
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.
Topics: Humans; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Gemcitabine; Pancreas; Neoadjuvant Therapy
PubMed: 38036745
DOI: 10.1038/s41575-023-00856-2 -
Science Translational Medicine Nov 2023Despite the success of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors in treating solid tumors, only a proportion of patients respond. Here, we...
Despite the success of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors in treating solid tumors, only a proportion of patients respond. Here, we describe a first-in-class bifunctional therapeutic molecule, STAR0602, that comprises an antibody targeting germline Vβ6 and Vβ10 T cell receptors (TCRs) fused to human interleukin-2 (IL-2) and simultaneously engages a nonclonal mode of TCR activation with costimulation to promote activation and expansion of αβ T cell subsets expressing distinct variable β (Vβ) TCR chains. In solution, STAR0602 binds IL-2 receptors in cis with Vβ6/Vβ10 TCRs on the same T cell, promoting expansion of human Vβ6 and Vβ10 CD4 and CD8 T cells that acquire an atypical central memory phenotype. Monotherapy with a mouse surrogate molecule induced durable tumor regression across six murine solid tumor models, including several refractory to anti-PD-1. Analysis of murine tumor-infiltrating lymphocyte (TIL) transcriptomes revealed that expanded Vβ T cells acquired a distinct effector memory phenotype with suppression of genes associated with T cell exhaustion and TCR signaling repression. Sequencing of TIL TCRs also revealed an increased T cell repertoire diversity within targeted Vβ T cell subsets, suggesting clonal revival of tumor T cell responses. These immunological and antitumor effects in mice were recapitulated in studies of STAR0602 in nonhuman primates and human ex vivo models, wherein STAR0602 boosted human antigen-specific T cell responses and killing of tumor organoids. Thus, STAR0602 represents a distinct class of T cell-activating molecules with the potential to deliver enhanced antitumor activity in checkpoint inhibitor-refractory settings.
Topics: Humans; Animals; Mice; Receptors, Antigen, T-Cell, alpha-beta; CD8-Positive T-Lymphocytes; Programmed Cell Death 1 Receptor; Receptors, Antigen, T-Cell; Neoplasms; Antibodies
PubMed: 38019931
DOI: 10.1126/scitranslmed.adi0258 -
Drug and Alcohol Dependence Dec 2023Contingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Contingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One important goal of optimization is decreasing drug use during the early stages of treatment, which has predicted success in other interventions. However, this "critical period" has not been reported in CM trials. The purpose of this analysis was to determine if, after accounting for baseline abstinence and incentive condition, abstinence in a CM trial for people with Cocaine Use Disorder (CUD) could be predicted by cocaine use during a first-week critical period.
METHODS
Eighty-seven participants with CUD were randomized to receive contingent high or low value incentives for cocaine abstinence or were in a non-contingent control group. Generalized estimating equations (GEE) were used to analyze urine test results over 36 timepoints during the 12-week intervention. To assess for a critical period, the first three visits were included in the GEE as a covariate for remaining urine test results.
RESULTS
Participants who provided more negative samples during the critical period were significantly more likely to produce a negative urine sample during the remainder of the trial, though some effects of group remained after controlling for the critical period.
CONCLUSIONS
These results indicate that a critical period exists for CM trials, and it can explain a substantial amount of future performance. Early contact with an abstinence-contingent high magnitude alternative reinforcer may explain additional performance beyond the critical period, further justifying the use of high magnitude alternative reinforcers.
Topics: Humans; Cocaine; Substance-Related Disorders; Cocaine-Related Disorders; Behavior Therapy; Motivation; Treatment Outcome
PubMed: 38006674
DOI: 10.1016/j.drugalcdep.2023.111030