BACKGROUND: The Pacific trial reported improved outcomes when durvalumab was administered following concurrent chemoradiotherapy (CRT) for stage III NSCLC. Post-hoc subgroup analysis did not show favorable results for PD-L1 negative cases. We compared nationwide survival data with the trial outcomes, and evaluated the influence of PD-L1.
METHODS: Data from the Netherlands Cancer Registry were queried regarding patients with clinical stage III who underwent CRT, either by concurrent or sequential administration. Predictors for the use of consolidation treatment with durvalumab were evaluated by tabulations and logistic regression analysis. Overall survival (OS) was calculated from start of radiation or start of durvalumab and was stratified by PD-L1 score.
RESULTS: Between 2017 and 2021, application of consolidation durvalumab increased from 2% to 21%, 40%, 57%, 62%, respectively. In the period 2020-2021, durvalumab use was more frequent among patients with younger age, concurrent CRT, better performance score and proton radiation, but was irrespective of PD-L1 score. For patients receiving durvalumab (n = 1639), the 4-year OS was 53% overall (95%CI 50-57), and it was 56% (95%CI 52-60) after concurrent CRT. Four-year OS was considerably better for the PD-L1 subgroup ≧50% at 67% (95%CI 59-73), and it was similar for PD-L1 subgroups 0 and 1-49, at 51% (95%CI 42-58) and 46% (95%CI 39-54), respectively.
CONCLUSIONS: In real-world clinical practice, survival outcomes were equivalent to results from trial series. Overall survival in patients with negative PD-L1 was similar to the survival in patients with PD-L1 1-49, questioning the restrictions imposed by the European Medicines Agency.

UNASSIGNED: All Nordic countries have national cancer registries collecting data on head and neck cancer (HNC) incidence and survival. However, there is a lack of consensus on how other quality aspects should be monitored.
UNASSIGNED: We conducted a web-based survey to find opportunities for quality control and improvement.
UNASSIGNED: A web-based survey was sent to one otorhinolaryngology - head and neck (ORL-HN) surgeon, and one oncologist at each Nordic university hospital treating HNC. In total, 42 responses from all 21 university hospitals were included.
UNASSIGNED: In over half of the university hospitals, an oncologist, an ORL-HN surgeon, a pathologist, a radiologist, and a specialized nurse was always present at the multidisciplinary tumor board (MTB) meeting. Of 42 respondents 35 (83%) agreed that treatment delays were systematically recorded for each patient. Eleven of 21 (52%) oncologists agreed that side-effects of (chemo)radiotherapy were systematically recorded. Less than half of the respondents agreed that complications of surgery, and post-treatment quality of life (QOL) were systematically recorded.
UNASSIGNED: In the Nordic countries, the importance of HNC treatment timelines is well acknowledged. There is a lack of consensus on the composition of MTB meeting, and how treatment-related morbidity should be monitored outside clinical trials.

BACKGROUND: During COVID-19 pandemic, the emergency department (ED) was challenged to treat patients with COVID-19-related symptom. Therefore, the aim of this study was to investigate treatment delay and prognostic outcomes in ST-segment elevation myocardial infarction (STEMI) patients during COVID-19 pandemic due to isolation or precaution and compare it with pre-COVID-19 period.
METHODS: This was a retrospective observation study using multicenter data with different case mix. Anonymized data were collected through each center\'s electronic medical data of common case report form. Primary outcomes were number and rate of in-hospital mortality within 28 days. Secondary outcomes were door-to-balloon time and length of stay in the ED. Kaplan-Meier estimation and Cox proportional hazard regression analysis were performed to determine impact of predictors on 28-day in-hospital mortality.
RESULTS: Door-to-balloon time was longer in STEMI patients with COVID-19-related symptom(s) than those without symptom during the COVID-19 period (97.0 [74.8, 139.8] vs. 69.0 [55.0, 102.0] minutes, P<.001). However, there was no significant statistical difference in door-to-balloon time between STEMI patients with and without COVID-19-related symptom(s) during the pre-COVID-19 period (73.0 [61.0, 92.0] vs. 67.0 [54.5, 80.0] minutes, P=.2869). The 28-day mortality rate did not show a statistically significant difference depending on symptoms suggestive of COVID-19 during the pre-COVID-19 period (15.4% vs. 6.8%, P=.1257). However, it was significantly higher during the COVID-19 period (21.1% vs. 6.7%, P=.0102) in patients with COVID-19 suggestive symptoms than in patients without the symptoms.
CONCLUSIONS: In Korea, symptoms suggestive of COVID-19 during the pandemic had a significant effect on the increase of door-to-balloon time and 28-day mortality in STEMI patients. Thus, health authorities need to make careful decision in designating symptoms indicated for isolation in ED based on opinions of various medical field experts.

UNASSIGNED: Initiating treatment within the optimal time is critical for women with breast cancer. A delay in cancer treatment initiation can result in increased morbidity and mortality and decreased overall survival.
UNASSIGNED: This systematic review aims to investigate the literature for the factors and beliefs affecting women diagnosed with breast cancer with regard to initiating cancer treatment.
UNASSIGNED: The PubMed, CINAHL, and PsycINFO databases were searched using the terms of breast cancer, initiating or seeking treatment, and beliefs. The Johns Hopkins Evidence-Based Practice Research Evidence Appraisal Tool was used to evaluate the included articles.
UNASSIGNED: Sixteen articles were included in this review. The addressed factors were classified as (1) patient-related factors, (2) disease-related factors, (3) provider-related factors, and (4) system-related factors. The identified beliefs were cultural beliefs and perceived barriers to initiating treatment.
UNASSIGNED: Although the literature reported multiple factors and beliefs that impact the time of initiating treatment among women with breast cancer, more research is needed to fully understand the beliefs influencing treatment initiation. It is essential to address and screen the factors and beliefs identified for women diagnosed with breast cancer to enhance treatment initiation early and prevent any possible delay. Interventions can be developed to overcome the factors and beliefs that may lead to late treatment initiation. Advocacy for new policies should be in action to reduce the disparities associated with treatment initiation among women with breast cancer.

OBJECTIVE: To identify diagnostic opportunities, we investigated healthcare-seeking behaviour among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis.
METHODS: We conducted a population-based, nationwide matched nested case-control study (Denmark, 2009-2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population and matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-month proportions of individuals with exposures and calculated absolute risk differences with corresponding 95% CI.
RESULTS: We included 1056 cases with LNB and 10 560 controls. Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95% CI: 10.9-15.1). Cases with LNB exhibited increased contact with most specialties, particularly general practitioners (difference: 48.7%, 95% CI: 46.0-51.4), neurology (difference: 14.3%, 95% CI: 11.7-16.8), and internal medicine (difference: 11.1%, 95% CI: 8.7-13.5), and medical wandering (difference: 17.1%, 95% CI: 14.3-20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95% CI: 8.3-12.1), the spine (difference: 8.8%, 85% CI: 7.0-10.6), and the abdomen (difference: 7.2%, 95% CI: 5.4-9.1). The increase in healthcare-seeking behaviour was observed ≤12 weeks preceding diagnosis.
CONCLUSIONS: Pain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behaviour preceding diagnosis is distributed across many medical specialties.

Objectives  Head and neck mucosal melanoma (HNMM) is a rare malignancy with high mortality. This study evaluates the impact of treatment delays on overall survival in HNMM. Design/Setting/Participants  A retrospective review of patients with surgically managed HNMM treated with adjuvant radiation was performed from the 2004-2016 National Cancer Database. Main Outcome Measures  Durations of diagnosis-to-treatment initiation (DTI), surgery-to-radiotherapy initiation (SRT), duration of radiotherapy (RTD), surgery-to-immunotherapy initiation (SIT), diagnosis-to-treatment end (DTE), and total treatment package (TTP) were calculated. Results  A total of 1,011 patients (50.7% female, 90.5% Caucasian) met inclusion criteria. Median DTI, SRT, RTD, SIT, DTE, and TTP were 30, 49, 41, 102, 119, and 87 days, respectively. Only longer DTE was associated with decreased mortality (hazard ratio, 0.720; 95% confidence interval, 0.536-0.965; p  = 0.028). Conclusion  DTI, SRT, RTD, SIT, and TTP do not significantly affect overall survival in patients with HNMM who undergo surgery and adjuvant radiation. Longer DTE is associated with improved survival in this population. Level of Evidence  4.

BACKGROUND: The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021.
METHODS: An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays.
RESULTS: We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic\'s beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic\'s start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level.
CONCLUSIONS: Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.

We show that redox active iron can induce a regulated form of non-apoptotic cell death and tissue damage called ferroptosis that can contribute to secondary damage and functional loss in the acute and chronic periods after spinal cord injury (SCI) in young, adult, female mice. Phagocytosis of red blood cells at sites of hemorrhage is the main source of iron derived from hemoglobin after SCI. Expression of hemeoxygenase-1 that induces release of iron from heme, is increased in spinal cord macrophages 7 days after injury. While iron is stored safely in ferritin in the injured spinal cord, it can, however, be released by NCOA4-mediated shuttling of ferritin to autophagosomes for degradation (ferritinophagy). This leads to the release of redox active iron that can cause free radical damage. Expression of NCOA4 is increased after SCI, mainly in macrophages. Increase in the ratio of redox active ferrous (Fe2+) to ferric iron (Fe3+) is also detected after SCI by capillary electrophoresis inductively coupled mass spectrometry. These changes are accompanied by other hallmarks of ferroptosis, i.e., deficiency in various elements of the antioxidant glutathione (GSH) pathway. We also detect increases in enzymes that repair membrane lipids (ACSL4 and LPCAT3) and thus promote on-going ferroptosis. These changes are associated with increased levels of 4-hydroxynonenal (4-HNE), a toxic lipid peroxidation product. Mice with mild SCI (30 kdyne force) treated with the ferroptosis inhibitor (UAMC-3203-HCL) either early or delayed times after injury showed improvement in locomotor recovery and secondary damage. Cerebrospinal fluid and serum samples from human SCI cases show evidence of increased iron storage (ferritin), and other iron related molecules, and reduction in GSH. Collectively, these data suggest that ferroptosis contributes to secondary damage after SCI and highlights the possible use of ferroptosis inhibitors to treat SCI.

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BACKGROUND: There is the highest estimated number of patients with obstructive sleep apnea (OSA) in China. Early treatment could lead to fewer complications associated with OSA. This study aimed to analyze the factors influencing help-seeking from the first symptom discovery to treatment in OSA.
METHODS: Semi-structured interview outline was designed to conduct face-to-face interview based on the analyses of a great number of related literatures on the delay in seeking medical attention of patients with OSA. 15 patients diagnosed were interviewed between June 2021 to September 2022 in general hospital of Shenyang, Northeastern of China. Qualitative data was analyzed by content analysis using the Model of Pathways to Treatment.
RESULTS: Analyses identified factors contributing to elapsed time from first symptom discovery to received treatment that are linked to disease characteristic, patients, health system organization. Appraisal interval is most obvious for patients with OSA, but it is difficult to pinpoint precisely because the patients didn\'t remember exactly when the first symptom was detected.
CONCLUSIONS: Patients diagnosed with OSA didn\'t initially interpret the snore as a warning sign and even thought it was a blessing. The findings provided guidance or avenues for reducing elapsed time between the first symptom and received treatment.