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Journal of Clinical Oncology : Official... Apr 2024Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA...
PURPOSE
Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated.
METHODS
In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS).
RESULTS
Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively.
CONCLUSION
The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.
Topics: Humans; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; Carcinoma, Pancreatic Ductal; Fluorouracil; Leucovorin; Prognosis; Neoadjuvant Therapy
PubMed: 38315954
DOI: 10.1200/JCO.23.01311 -
Journal of Biomechanics Jan 2024It is generally accepted that the lifting technique strongly influences physical loads within the human body and, thus, the risk of musculoskeletal disorders. However,...
It is generally accepted that the lifting technique strongly influences physical loads within the human body and, thus, the risk of musculoskeletal disorders. However, there is a lack of knowledge regarding whether particular lifting techniques are effective in reducing loads. Hence, this retrospective study quantified (partly published) in vivo loads at joints within the human body during two typical lifting techniques, stoop lifting and squat lifting. Patients who had received instrumented implants underwent in vivo load measurements at either the knee (two patients), the hip (eight patients), or the upper lumbar spine (four patients) while lifting a 10 kg weight frontally with either straight (stoop) or bent (squat) knees. Contact forces and moments and the orientation of the contact force vector were determined and examined using the paired t test of Statistical Parametric Mapping. The two lifting techniques did not differ in terms of load magnitudes but did differ in terms of directions: (i) at the hip joint, the load vector varied significantly (p < 0.05) in the frontal and sagittal planes, (ii) at the knee joint, the load vector differed significantly (p < 0.05) in the sagittal plane (iii) while the load vector and magnitude did not differ at the upper lumbar spine (p > 0.05). Our findings indicate that the lifting technique causes changes in the orientation rather than the magnitude of lower extremity joint contact loads. Even though this quantification could only be performed in a small group of patients, the quantification of the relevance of such lifting technique recommendations will hopefully guide future recommendations towards a more scientific interpretation.
Topics: Humans; Lifting; Retrospective Studies; Spine; Knee; Knee Joint; Lumbar Vertebrae; Biomechanical Phenomena
PubMed: 38286711
DOI: 10.1016/j.jbiomech.2024.111963 -
Gut Apr 2024Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an... (Randomized Controlled Trial)
Randomized Controlled Trial
Standardised training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicentre cluster randomised trial.
OBJECTIVE
Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals.
DESIGN
In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months.
RESULTS
A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high.
CONCLUSION
A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm.
TRIAL REGISTRATION NUMBER
NTR7477.
Topics: Humans; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Endoscopic Mucosal Resection
PubMed: 38216328
DOI: 10.1136/gutjnl-2023-330020 -
Annals of Surgical Oncology Mar 2024
ASO Author Reflections: The Value of Serum CEA for Prognostication at Staging and Response Evaluation in Patients with Localized Pancreatic Adenocarcinoma and Nonelevated CA19-9.
Topics: Humans; CA-19-9 Antigen; Pancreatic Neoplasms; Adenocarcinoma; Biomarkers, Tumor; Carcinoembryonic Antigen; Prognosis; Neoplasm Staging
PubMed: 38182848
DOI: 10.1245/s10434-023-14815-3 -
BMC Health Services Research Jan 2024Relocations within and between nursing homes often induce stress, anxiety, and depression in residents and cause additional workload for and burnout in staff. To prevent...
BACKGROUND
Relocations within and between nursing homes often induce stress, anxiety, and depression in residents and cause additional workload for and burnout in staff. To prevent this, many nursing homes deploy pre-transition initiatives, bridging initiatives, and post-transition initiatives to support residents and staff during the relocation process. As little is known about these initiatives, this study aims to explore the pre-relocation, bridging and post-relocation initiatives used for relocations within and between nursing homes.
METHODS
In seven Dutch nursing homes, eight focus groups were conducted with two to six participants (N = 37) who were actively involved in relocation processes in different roles (i.e., managers, healthcare professionals, support staff, client council members, residents and family). The focus groups were conducted based on a predefined topic list and lasted approximately 60 min. The transcripts were recorded, transcribed verbatim and analysed using thematic coding.
RESULTS
Nursing homes had to be inventive in developing relocation initiatives as neither shared guidelines nor knowledge exchange on this topic were available. A total of thirty-seven relocation initiatives were identified in these seven nursing homes. Nineteen pre-relocation initiatives were identified, of which eight emphasized information and engagement, three highlighted training and practice and eight stressed orientation and visualization. Seven bridging initiatives were identified, of which four emphasized coordination and continuity and three highlighted entertainment and celebration. Eleven post-relocation initiatives were identified, of which seven emphasized evaluation and troubleshooting and four highlighted change and adjustment.
CONCLUSION
The identified relocation initiatives were developed unassisted by nursing homes, due to a lack of shared guidelines, knowledge exchange and mutual learning on this topic. Therefore, it may be expedient and more effective to develop general guidelines for relocations within and between nursing homes in collaboration with nursing homes.
Topics: Humans; Nursing Homes; Qualitative Research; Focus Groups; Health Personnel; Anxiety
PubMed: 38178063
DOI: 10.1186/s12913-023-10505-8 -
Annals of Surgical Oncology Mar 2024About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of...
Serum CEA as a Prognostic Marker for Overall Survival in Patients with Localized Pancreatic Adenocarcinoma and Non-Elevated CA19-9 Levels Treated with FOLFIRINOX as Initial Treatment: A TAPS Consortium Study.
INTRODUCTION
About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative.
METHODS
This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics.
RESULTS
Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not.
CONCLUSIONS
Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.
Topics: Humans; Pancreatic Neoplasms; Carcinoembryonic Antigen; CA-19-9 Antigen; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Prognosis; Retrospective Studies; Adenocarcinoma; Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil
PubMed: 38170408
DOI: 10.1245/s10434-023-14680-0 -
Neonatology 2024Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated...
The Utility of Urinary NGAL as an Alternative for Serum Creatinine to Detect Acute Kidney Injury in Infants Exposed to Nephrotoxic Medications in the Neonatal Intensive Care Unit.
INTRODUCTION
Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program.
METHODS
This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to 7 days of NTM exposure plus 2 days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs.
RESULTS
The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3-100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39-4.13).
DISCUSSION/CONCLUSION
We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.
Topics: Infant; Infant, Newborn; Humans; Lipocalin-2; Intensive Care Units, Neonatal; Creatinine; Prospective Studies; Biomarkers; Acute Kidney Injury
PubMed: 38151013
DOI: 10.1159/000535322 -
Neuropharmacology Mar 2024The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an...
The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.
Topics: Male; Female; Animals; Rats; Xylazine; Fentanyl; Analgesics, Opioid; Acute Disease; Clonidine; Substance Withdrawal Syndrome; Weight Loss; Body Weight
PubMed: 38128606
DOI: 10.1016/j.neuropharm.2023.109816 -
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