Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non-anthracycline-based regimen in TOP2A-normal patients. ...Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m
) and cyclophosphamide (600 mg/m
) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m
) and cyclophosphamide (600 mg/m
) followed by three cycles of docetaxel (100 mg/m
; EC-D). The primary end point was disease-free survival (DFS) after a median of 5 years of follow-up. Secondary end points were patient-reported toxicity, overall survival (OS), and distant disease-free survival. Results At a median estimated potential follow-up of 69 months, 5-year DFS was 87.9% (95% CI, 85.6% to 89.8%) in the EC-D arm and 88.3% (95% CI, 86.1% to 90.1%) in the DC arm. There was no significant difference in the risk of DFS events (hazard ratio HR, 1.00; 95% CI, 0.78 to 1.28; P = 1.00), distant disease-free survival (HR, 1.12; 95% CI, 0.86 to 1.47; P = .40), or mortality (HR, 1.15; 95% CI, 0.83 to 1.59; P = .41) in the intent-to-treat analysis. A significant interaction between menopausal status and treatment group was observed for DFS ( P = .04) but not for OS ( P = .07). Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.
For development of hollow-core transmission fibers, the realizable fibers lengths, bandwidth, characterization, and compatibility with standard technology are important issues. We report ...record-length air-guiding fiber, spectral properties, splicing, and optical time domain reflectometer (OTDR) measurements. Furthermore, spectral macrobending loss measurements for two different designs of air-core photonic bandgap fibers are presented. While bending loss is observed, it does not limit operation for all practical bending diameters (>5 mm).
High-dose prednisolone is used in first-line treatment for lymphoma, but the potential adverse impact on bone health is unclear. Danish patients with diffuse large B-cell lymphoma or follicular ...lymphoma diagnosed between 2000 and 2012 were matched to the background population. Osteoporotic events (osteoporosis treatment or low-energy fracture) were identified using the Danish National Patient Registry and Prescription Registry. In total, 2589 patients and 12,945 controls were included. Lymphoma patients had increased risk of osteoporotic events compared to the matched population (hazard ratio 1.61 95% confidence interval 1.40;1.84). The 5- and 10-year cumulative risks of osteoporotic events for lymphoma patients were 10.0% 8.6;11.4 and 16.3% 13.8;18.7, whereas corresponding risks in the background population were 6.8% 6.3;7.3 and 13.5% 12.4;14.6. Patients without osteoporotic event in the first two years after treatment were not at higher risk of osteoporotic events in subsequent years. Risk factors for osteoporotic events were female sex and age >70 years.
: We have analyzed the expression of synaptic vesicle proteins in human neuroendocrine tumors and the potential use of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. ...Biopsies from endocrine and nonendocrine tumors of the gastrointestinal tract, pancreas, and adrenals were examined by immunocytochemistry using antibodies against synaptic vesicle protein 2 (SV2), vesicular monoamine transporter 1 and 2 (VMAT1&2), and neuroendocrine secretory protein 55 (NESP55). SV2 was expressed in all endocrine tumors of the gastrointestinal tract and pancreas as well as in gastrointestinal stromal tumors (GISTs). None of the adenocarcinomas expressed SV2. VMAT1&2 were expressed in amine‐producing tumors of the gastrointestinal tract (ECL cell and EC cell carcinoids) and in a small number of peptide‐producing pancreatic endocrine tumors. NESP55 was expressed in neuroblastomas and adrenal pheochromocytomas as well as in a subgroup of pancreatic endocrine tumors. The importance of VMAT1&2 for the uptake of 123I‐MIBG in tumor cells was demonstrated. It was concluded that neuroendocrine tumors express multiple synaptic vesicle proteins that are useful in the histopathological diagnosis and classification of tumors. Vesicle proteins may prove to be useful for targeting tumor therapy.
Metronomic treatment is hypothesized to be less toxic and more effective as compared to standard maximal tolerable dosing treatment in metastatic cancer disease.
We tested the metronomic treatment ...principle with vinorelbine in a randomized phase 2 setting combined with standard capecitabine treatment in the XeNa trial with Clinical Trials.gov identifier number: NCT0141771. 120 patients with disseminated HER2 non-amplified breast cancer were included. Randomization was between Arm A: vinorelbine 60 mg/m
2
day 1 + day 8 in the first cycle followed by 80 mg/m
2
day 1 + day 8 in the following cycles or Arm B: vinorelbine 50 mg three times a week. Capecitabine 1000 mg/m
2
twice a day for days 1-14 was administered in both arms.
The treatment was generally well-tolerated. The response rate (RR) was 24% (arm A) versus 29% (arm B) (p = .67). The clinical benefit rate (CBR) 46.8% (arm A) versus 51.7% (arm B) (p = .72). We found a median progression-free survival (PFS) of 7.1 months (95% confidence interval CI 3.9-10.3) in arm A and 6.3 months (95% CI 4.1-8.5) in arm B (p = .25) whereas median overall survival (OS) was 23.3 months (95% CI 20.2-26.4) in arm A and 22.3 months (95% CI 14.3-30.3) in arm B (p = .76).
We confirmed that the combination of vinorelbine and capecitabine was well tolerated. Metronomic treatment can be used with acceptable adverse events (AEs), but we did not find significant difference in the effect compared to the standard treatment.
Geographical setting is seldomly taken into account when investigating out-of-hospital cardiac arrest (OHCA). It is a common notion that living in rural areas means a lower chance of fast and ...effective helpwhen suffering a time-critical event. This retrospective cohort study investigates this hypothesis and compares across healthcare-divided administrative regions.
We included only witnessed OHCAs to minimize the risk that outcome was predetermined by time to caller arrival and/or recognition. Arrests were divided into public and residential. Residential arrests were categorized according to population density of the area in which they occurred. We investigated incidence, EMS response time and 30-day survival according to area type and subsidiarily by healthcare-divided administrative region.
The majority (71%) of 8,579 OHCAs were residential, and 53.2% of all arrests occurred in the most densely populated cell group amongst residential arrests. This group had a median EMS response time of six minutes, whereas the most sparsely populated group had a median of 10 minutes. Public arrests also had a median response time of six minutes. 30-day survival was highest in public arrests (38.5%, 95% CI 36.9;40.1), and varied only slightly with no statistical significance between OHCAs in densely and sparsely populated areas from 14.8% (95% CI 14.4;15.2) and 13.4% (95% CI 12.2;14.7).
Our study demonstrates that while EMS response times in Denmark are longer in the rural areas, there is no statistically significant decrease in survival compared to the most densely populated areas.
Postoperative delirium (POD) following surgery is a prevalent and distressing condition associated with adverse patient outcomes and an increased healthcare burden.
To assess the effectiveness of the ...Safe Brain Initiative care bundle (SBI-CB) in reducing POD in the postanesthesia care unit (PACU).
A multicenter, quality-improvement initiative with retrospective analysis of collected data.
The study was conducted in the operating rooms and postanesthesia care units (PACUs) of four hospitals across Denmark and Turkey.
The convenience sample of patients were aged ≥18 years, scheduled for surgery, and could communicate verbally. Age, sex, preoperative delirium, and the American Society for Anesthesiology physical status classification were used in statistical methods to control for potential confounding influences.
The SBI-CB, 18 delirium-reducing recommendations aligned with international guidelines. The intervention included patient education, staff training, coordination meetings across centers, and a dashboard for the monitoring of outcomes in the PACU.
The primary outcome was the POD trend in the PACU during implementation months, assessed through Nu-DESC screening at up to three time points in the PACU. We also examined the length of hospital stay.
Data were collected from 18,697 adult patients across four hospitals. Initial POD incidence in the PACU after the first three months was 16.36% across all sites (n = 1021). POD in the PACU was observed across all age groups, with peak incidence in younger (18–35 years) and older (>75 years) patients. General anesthesia and longer surgical duration (>1 h) were identified as significant risk factors for POD in the PACU. Matched patients who experienced POD in the PACU had longer stays in hospital, with a mean increase from 35 to 69 h (p < 0.001). Implementation of the SBI-CB was associated with a decreased risk of POD in the PACU for each month of SBI-CB implementation (adjusted odds ratio 0.96, 95% confidence interval: 0.94, 0.97, p < 0.001).
The presented pragmatic implementation of a multidisciplinary care bundle, encompassing pre-, intra-, and postoperative measures alongside outcome monitoring, has the potential to significantly reduce the incidence of POD in the PACU. Improved patient outcomes may be achieved for general surgical departments with patient cohorts not typically considered at risk for developing POD.
Trial Registration: Clinicaltrials.gov, identifier NCT05765162.
•Data was collected for 18,697 adult patients for a quality-improvement initiative, implementing a care bundle of 18 recommendations for improving patients' wellbeing and neurocognitive function in the perioperative phase, at four hospitals and data was analyzed retrospectively.•A significant reduction in the risk of postoperative delirium in the postanesthesia care unit was observed for at least 19 months after the care bundle was initiated.•Patients with postoperative delirium in the postanesthesia care unit stayed nearly twice as long in hospital on average.•Use of general anesthesia and surgical duration longer than one hour were identified as significant risk factors for postoperative delirium in the postanesthesia care unit.•Postoperative delirium in the postanesthesia care unit was observed in all adult age groups and peak incidence occurred in both younger and older adults.
Mycorrhizas are ubiquitous symbioses that may have an important role in the movement of C from air to soil. Studies on the effects of climate change factors on mycorrhizas have been concentrated on ...the effects of atmospheric CO2 whereas temperature effects have been neglected. Based on previous results showing no effect of varying atmospheric CO2 on the development and P uptake of the arbuscular mycorrhizal fungi (AMF) colonizing plants growing in controlled conditions, we hypothesized that soil temperature would have a higher impact on AMF development and nutrient uptake than the effects of CO2 on the host plant. Pea plants were grown in association with either a single isolate of Glomus caledonium or AMF from field soil in factorial combination with the corresponding current (10 °C) or elevated (15 °C) soil temperatures at current (350 p.p.m) or elevated (700 p.p.m) atmospheric CO2. 33P uptake by extraradical AMF hyphae was measured independently from root P uptake in a root exclusion compartment. Intraradical colonization developed well at both soil temperatures and almost duplicated from 10 to 15 °C. Extraradical mycelium developed only at 15 °C in the root exclusion compartment and hyphal P uptake could therefore be studied at 15 °C only. Hyphal P uptake differed markedly between inoculum types, but was not altered by growing the host plants at two atmospheric CO2 levels. No significant CO2 × soil temperature interactions were observed. The results suggested that, in the system tested, AMF development and function is likely more influenced by the temperature component of climate change than by its CO2 component. We suggest that much more attention should be paid to temperature effects in future studies.
Aim
The aim was to study anorectal function in long‐term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer.
Methods
This was a ...case–control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores.
Results
Thirteen RCPs (12 men, median age 68 years, range 52–92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur‐uracil with complete clinical response (median time since treatment 2.8 years, range 2.2–5.6) were compared to 15 NSs (14 men, median age 64 years, range 47–75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8–67.7) versus 58.8 mmHg (25.7–105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2–203) versus 188 mmHg (103–248) (P < 0.01). Squeeze‐induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 22–158 vs. 82 36–190 ml, P = 0.4) or at urge to defaecate (107 42–227 vs. 132 59–334 ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 59–319 vs. 222 106–447 ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0–39) for RCPs and 7 (0–23) for NSs (P < 0.001), while the Wexner score was 0 (0–5) versus 0 (0–4) (P = 0.56).
Conclusion
Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long‐term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.
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