Search

Pancreatic cancer is among the most immune-resistant tumor types due to its unique tumor microenvironment and low cancer immunogenicity. Single-agent immune modulators have thus far proven clinically ineffective. However, a growing body of evidence suggests that combination of these modulators with other strategies could unlock the potential of immunotherapy in pancreatic cancer. Herein, we describe the case of a 59-year-old male with metastatic pancreatic ductal adenocarcinoma, referred to our center to receive immunotherapy (serplulimab, a novel anti-PD-1 antibody) combined with chemotherapy (gemcitabine/nab-paclitaxel). During the initial three treatment cycles, the patient was assessed as having stable disease (SD) according to RECIST 1.1 criteria. However, following two additional cycles of combination therapy, the primary tumor mass increased from 4.9 cm to 13.2 cm, accompanied by the development of new lung lesions, ascites, and pelvic metastases. He succumbed to respiratory failure one month later. Retrospective analysis revealed that the patient had MDM4 amplification, identified as a high-risk factor for hyperprogressive disease (HPD). To our knowledge, this is the first reported case of HPD in pancreatic cancer with multiple metastases treated using combination therapy. We investigated the potential mechanisms and reviewed the latest literature on predictive factors for HPD. These findings suggest that while chemotherapy combined with immunotherapy may hold promise for treating pancreatic cancer, it is imperative to identify and closely monitor patients with high-risk factors for HPD when using immunotherapy., (© 2024. The Author(s).)

Objective: To summarise the effectiveness of digital health maintenance interventions for subjectively and objectively measured physical activity level (PA) and physical function, fitness and health-related quality of life (HRQoL) after completion of phase II cardiac rehabilitation (CR)., Methods: We conducted a search for studies in MEDLINE, Embase, CENTRAL, and CINAHL (inception to May 2024). Independent reviewers selected and included randomised controlled trials (RCTs) using digital health interventions to maintain PA in patients with cardiovascular disease after phase II CR. Independent reviewers conducted data extraction, assessed the risk of bias using the Cochrane Risk of Bias 2 tool and rated the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation - registered at PROSPERO: CRD42023396629., Results: From 17,455 hits, 20 RCTs with 1801 participants were included. Risk of bias for most studies reporting on PA outcomes was rated as 'some concerns'. Comparing digital health intervention with minimal intervention/usual care showed no effect of objective PA (standardised mean difference (SMD) 0.85, 95% CI: -0.07 to 1.77) and a small effect of subjective PA (SMD 0.37, 95% CI: 0.05 to 0.69) at the end of intervention both graded as very low certainty of evidence. We found very low certainty of evidence for moderate effects on physical function (SMD 0.63, 95% CI: 0.03 to 1.24), and low certainty of evidence for no effect on physical fitness (SMD 0.19, 95% CI: 0.05 to 0.34) and HRQoL (SMD 0.13, 95% CI: -0.02 to 0.28), I 2 = 0.00%) at the end of intervention., Conclusion: Digital health interventions showed a small effect on subjectively measured PA, and no effect on objective PA, physical fitness and HRQoL, but may increase physical function after CR completion. Yet, the certainty of evidence is low and higher quality studies with longer follow-up duration are needed to guide this area further., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

This study presents two cases of lipid-rich pancreatic neuroendocrine tumors (PanNETs), a rare variant posing significant diagnostic challenges in fine needle aspiration (FNA) cytology and small biopsies. The first case involves an elderly male with a pancreatic tumor, displaying distinct cytoplasmic vacuoles, while the second case is a middle-aged male present with a pancreatic tail mass exhibiting foamy cytoplasm and eccentric nuclei, infiltrating in the stroma. Both cases did not exhibit typical morphologic features of PanNET but demonstrated cytomorphologic features and infiltrative growth patterns that mimicked adenocarcinoma. Further work-up demonstrated that both tumors were immunoreactive for synaptophysin and chromogranin, and were interpreted as well-differentiated, PanNET, lipid-rich variant. The study highlights the overlapping morphological features between lipid-rich PanNETs and other pancreatic neoplasms and underscores the importance of comprehensive cytological and immunohistochemical analysis for accurately diagnosing this variant, particularly due to the risk of misinterpreting it as pancreatic adenocarcinoma. Recognizing lipid-rich PanNETs is crucial for appropriate clinical management, as their identification can significantly impact treatment decisions and patient outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Lymph node metastasis is a critical prognostic factor for patients with gastric carcinoma (GC). Sentinel lymph node (SLN) mapping has the potential to identify the initial site of draining lymph node metastasis and reduce the extent of surgical lymphadenectomy. This study aimed to evaluate the diagnostic accuracy of SLN mapping in GC., Methods: The study enrolled 129 GC patients undergoing total or partial gastrectomy with D2 lymphadenectomy and indocyanine green fluorescence-guided SLN mapping. The primary outcomes were the negative predictive value (NPV) and sensitivity of SLN mapping. The secondary outcomes were clinicopathologic factors associated with SLN mapping accuracy and successful SLN mapping., Results: The SLN detection rate in this study was 86.8 %. The study had an overall NPV of 83.1 % and an overall sensitivity of 65.8 %. The NPV was found to be significantly higher in the patients with no lymphovascular invasion (LVI) than in those with LVI (96.0 % vs 59.3 %; p < 0.001) and in the patients whose pathologic T (pT) stage lower than 3 than in those whose T stage was 3 or higher (92.0 % vs 66.7 %; p = 0.009). The sensitivity of SLN mapping was 50 % in the patients with no LVI and 33 % in the patients with a pT stage lower than 3., Conclusion: The study results showed that for patients with early-stage GC with no LVI, negative SLN findings may represent a potential additive predictor indicating the absence of regional LN metastasis. However, given the low sensitivity rates noted, further research is needed to identify specific patient populations that may benefit from SLN mapping in GC., (© 2024. Society of Surgical Oncology.)

Purpose: The clinical course of pulmonary carcinoids ranges from indolent to fatal disease, suggesting that specific molecular alterations drive progression toward the fully malignant state. A similar spectrum of clinical phenotypes occurs in pediatric neuroblastoma, in which activation of telomerase reverse transcriptase ( TERT ) is decisive in determining the course of disease. We therefore investigated whether TERT expression defines the clinical fate of patients with pulmonary carcinoid., Methods: TERT expression was examined by RNA sequencing in a test cohort and a validation cohort of pulmonary carcinoids (n = 88 and n = 105, respectively). A natural TERT expression cutoff was determined in the test cohort on the basis of the distribution of TERT expression, and its prognostic value was assessed by Kaplan-Meier survival estimates and multivariable analyses. Telomerase activity was validated by telomere repeat amplification protocol assay., Results: Similar to neuroblastoma, TERT expression exhibited a bimodal distribution in pulmonary carcinoids, separating tumors into TERT -high and TERT- low subgroups. A natural TERT cutoff discriminated unfavorable from favorable clinical courses with high accuracy both in the test cohort (5-year overall survival [OS], 0.547 ± 0.132 v 1.0; P < .001) and the validation cohort (5-year OS, 0.788 ± 0.063 v 0.913 ± 0.048; P < .001). In line with these findings, telomerase activity was largely absent in TERT -low tumors, whereas it was readily detectable in TERT- high carcinoids. In multivariable analysis considering TERT expression, histology (typical v atypical carcinoid), and stage (≤IIA v ≥IIB), high TERT expression was an independent prognostic marker for poor survival, with a hazard ratio of 5.243 (95% CI, 1.943 to 14.148; P = .001)., Conclusion: Our data demonstrate that high TERT expression defines clinically aggressive pulmonary carcinoids with fatal outcome, similar to neuroblastoma, indicating that activation of TERT may be a defining feature of lethal cancers.

Background: Cardiac rehabilitation (CR) is recommended following acute coronary syndrome (ACS). Diabetes is a common long-term condition associated with ACS, and the inclusion of these patients in CR has been less studied. This study examines the referral, uptake, and completion rates in the CR pathway for ACS patients with and without diabetes to identify potential barriers in the CR pathway., Methods: The study included patients aged 18 or above who were discharged after a diagnosis of ACS in the Central Denmark Region between 1 September 2017 and 31 August 2018. Diabetes information was obtained from three sources. Logistic regression models were used to examine the associations between having diabetes and the three outcomes: non-referral, non-uptake and non-completion. Results were reported as odds ratios (OR) with 95% confidence intervals (CI)., Results: A total of 2447 patients were eligible for the study, of which 457 (18.7%) had diabetes. Only non-uptake was found to be significantly associated with diabetes after adjustment for prespecified variables (OR = 1.38, 95% CI 1.01-1.90). Associations for non-referral (OR = 1.11, 95% CI 0.87-1.41) and non-completion (OR = 1.06, 95 %CI 0.73-1.53) were not found to be statistically significant between ACS patients with diabetes and those without diabetes., Conclusion: This study highlights a significant disparity in the uptake of CR between patients with and without diabetes following ACS, demonstrating that patients with diabetes require early promotion and increased assistance to enrol in CR., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Little is known about delivering telehealth from a healthcare provider's perspective., Purpose: To investigate physiotherapists' (PTs) experiences in delivering live online exercise and education for people with knee osteoarthritis (OA)., Methods: This was a qualitative individual interview study with a thematic analysis approach. The interviewees were six PTs delivering 8 weeks of supervised online exercise and education for people with knee OA in secondary public care in Denmark., Results: The three main themes were (1) From hands to words-on the transition from on-site to on-line physiotherapy, (2) Online selection-on the perceived barriers to managing a telehealth service and (3) Therapeutic relation under pressure-on the contextual difficulties in building relationships and alliances in online classes., Conclusion: The PTs in this study seemed to gradually come to terms with delivering first-line OA care online, appreciating advantages and new possibilities. PTs' initial apprehension towards this new form of physiotherapy service may be rooted in the traditional conception of physiotherapy as a predominantly manual profession but also in a lack of formal training in physiotherapy telehealth services. This study underlines the growing need for better and more formalised training in physiotherapy telehealth services to meet growing demands., (© 2024 The Author(s). Musculoskeletal Care published by John Wiley & Sons Ltd.)

Background: The incidence of diffuse-type gastric cancer is increasing steadily in the United States, Europe, and Asia. This subtype is known for aggressive clinical characteristics and transmural invasion. However, T1a diffuse-type cancers have been observed to have a better 5-year, disease-specific mortality than stage-matched intestinal tumors, supporting a clinical difference in these early-stage cancers., Methods: Data on all living patients with T1a gastric adenocarcinoma with a finding of signet ring cell morphology on pathology and ≥1 year of follow-up from 2013 to 2023 at Memorial Sloan Kettering Cancer Center (MSK) was collected from a prospectively maintained database. Patients with known CDH1 or CTNNA1 mutations were excluded., Results: In 7 of 30 patients, sporadic pathologically confirmed T1a signet ring cell (diffuse) cancer identified on initial biopsy was no longer detectable upon subsequent biopsy or resection with mean follow-up of 50 months., Conclusions: These cases allude to the distinct pathways of carcinogenesis in T1a signet ring cell cancers. Potential factors that may underlie the spontaneous regression of these T1a cancers include complete removal at initial biopsy, immune clearance, and lack of survival advantage conferred by signet ring cell genetic alterations in these cases. Given their more indolent behavior at an earlier stage, we suggest that these lesions can be closely followed by endoscopy in select circumstances with thorough disease assessment and an experienced care team., (© 2024. Society of Surgical Oncology.)

Arthritis affects many individuals and can cause pain and limit physical functioning. Exercise is an important treatment option for individuals with arthritis; however, adherence to exercise programs can be challenging. A new initiative in Denmark has introduced nature-based exercises for patients with arthritis. This qualitative study aimed to explore the experiences of the individuals who participated in those exercises. The study used a hermeneutic-phenomenological approach and conducted along-side interviews with 12 women and three men who participated in nature-based exercise programs for arthritis. Analysis of the data revealed two main themes. The first theme highlighted the positive effects of being in nature, such as increased vitality, reduced pain, and a sense of well-being. The second theme emphasized the social benefits of participating in these exercises, including a sense of connection and community with others. Overall, this study suggests that incorporating nature-based exercises in treatment programs for arthritis could have significant benefits for individuals with this condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: STS is associate editor of the Journal of Orthopaedic and Sports Physical Therapy, has received personal fees from Munksgaard, TrustMe-Ed, and Nestlé Health Science, outside the submitted work, and is co-founder of GLA:D®, a not-for-profit initiative hosted at the University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice. The authors have no other potential conflicts to disclose.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: The effects of physical activity on health are well-established for chronic diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and ischaemic heart disease (IHD). However, sustaining physical activity in everyday life is difficult. Lifeworld knowledge can help qualify interventions aimed at resolving this public health issue, but there is a gap in regard to synthesized research on peoples' experiences with integrating and sustaining physical activity. Hence, the purpose of this review is to explore and present the available evidence on experiences with integrating and sustaining physical activity in a lived life with MS, AD, and IHD., Methods: We conducted a scoping review with qualitative analysis and narrative syntheses in accordance with PRISMA-ScR. Based on SPIDER we ran a systematic search in Cinahl, Embase, Medline, and PsychInfo for primary qualitative research papers published until December 2022., Results: 43 papers were included. A thematic content analysis found that individuals who have MS, AD or IHD find integrating and sustaining physical activity in everyday life meaningful on several levels: Physical activity can facilitate meaningful movement with outcomes of physical, psychosocial, and existential importance., Conclusion: The research literature presents a meaning to physical activity that extends the idea of physical fitness to one of existential movement and personal growth. In addition, our review finds that people are more likely to integrate and sustain physical activity if they feel acknowledged, supported and believe that physical activity has a meaningful purpose reflecting their sense of self. Taking a more person-centred approach in rehabilitative care might help qualify the content of physical activity in terms of integration into everyday life, but more research is needed on how to implement a person-centred approach in practice.

Objective: To examine the benefits and harms of structured outdoor physical activity (PA) for people living with one or more somatic or mental diseases., Methods: We identified articles from inception until Marts 2023 in MEDLINE, EMBASE, CINAHL and CENTRAL and citation tracking in Web of Science. We included randomized controlled trials (RCTs) and observational studies examining structured outdoor PA reporting physical function, health-related quality of life (HRQOL), pain or mental outcomes. We used random-effect meta-analyses and investigated heterogeneity in subgroups, sensitivity and meta-regression analyses. Observational studies and studies with insufficient data were summarized narratively. Certainty of evidence was assessed with GRADE., Results: From 4098 hits, 20 studies (19 RCTs and 1 cohort) were included (n: 1759 participants). Studies varied in type of disease and intervention. End of intervention results suggested a small effect on HRQOL (k = 10, SMD = 0.45, 95%CI: 0.19 to 0.71) and physical function (k = 14, SMD = 0.39, 95%CI: 0.13 to 0.64), while effects were moderate on mental outcomes (k = 13, SMD = -0.52, 95%CI: -0.82 to -0.23) favoring the outdoor intervention over comparators (no intervention, usual care, indoor PA or outdoor intervention without exercise). We were not able to conclude on outdoor interventions' effect on pain. Four studies reported adverse events including non-serious (pain, falls, fatigue) and serious (hospitalization, pneumonia). Certainty of evidence was overall very low., Conclusion: Structured outdoor PA may improve HRQOL and physical function, as well as mental health outcomes. The very low certainty of evidence calls for high quality RCTs to determine benefits and harms of structured outdoor PA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declared the following potential conflict of interest: STS is co-founder of GLA:D®, a not-for profit initiative hosted at University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice. Furthermore, he has received personal fees from Munksgaard, TrustMe-Ed, and Nestlé Health Science, outside the work. AB has received personal fees from PhisioVit S.r.l. JRA, HB, PMH, DVP and LHT have no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples., Methods: Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP., Results: Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA., Conclusion: This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.

Anti-programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease heterogeneity within individual tumor lesions or among several lesions within the same patient, the PD-L1 combined positive score is a dynamic biomarker subject to evolution throughout a patient's disease course, and repeated biopsies are invasive and not always feasible. Methods: This was a prospective pilot study of the PD-L1-targeting radiotracer, 18 F-BMS-986229, with PET imaging (PD-L1 PET) in patients with gastroesophageal cancer. Patients were administered the 18 F-BMS-986229 radiotracer intravenously at a dose of 370 MBq over 1-2 min and underwent whole-body PET/CT imaging 60 min later. The primary objective of this study was to evaluate the safety and feasibility of 18 F-BMS-986229. The trial is registered with ClinicalTrials.gov (NCT04161781). Results: Between February 3, 2020, and February 2, 2022, 10 patients with gastroesophageal adenocarcinoma underwent PD-L1 PET. There were no adverse events associated with the 18 F-BMS-986229 tracer, and imaging did not result in treatment delays; the primary endpoint was achieved. Radiographic evaluation of PD-L1 expression was concordant with pathologic assessment in 88% of biopsied lesions, and 18 F-BMS-986229 uptake on PET imaging correlated with pathologic evaluation by the combined positive score (Spearman rank correlation coefficient, 0.64). Seventy-one percent of patients with 18 F-BMS-986229 accumulation on PET imaging also had lesions without 18 F-BMS-986229 uptake, highlighting the intrapatient heterogeneity of PD-L1 expression. Patients treated with frontline programmed death 1 inhibitors who had 18 F-BMS-986229 accumulation in any lesions on PET imaging had longer progression-free survival than patients without tracer accumulation in any lesions (median progression-free survival, 28.4 vs. 9.9 mo), though the small sample size prevents any definitive conclusions. Conclusion: PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care., Methods: Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUV mean of liver to the average SUV mean of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS., Results: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009)., Conclusions: Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Purpose: To explore patients with cardiovascular diseases' lived experiences of the support given by a text message intervention focusing on the maintenance of physical activity after supervised cardiac rehabilitation., Methods: In a qualitative study, participants from the feasibility trial FAIR were interviewed individually twice to disclose their lived experiences during and after the trial. Transcribed interviews were analysed based on a phenomenological-hermeneutic method, inspired by Paul Ricoeur's philosophy on narrative and interpretation., Results: Interviews of eight patients with cardiovascular disease (3 females, median age 57 years (range 37 to 74 years)) revealed two themes, The FAIR intervention as a bridge builder in the transition to being physically active in everyday life and Meaningful conditions for maintaining physical activity . Action plans guided physical activity, while text messages facilitated actions and left an impression of still being under supervision. A frame of reference with physical activity, family, being monitored, having to report back, and getting feedback, were incentives for being physically active., Conclusion: From a patient perspective, the text message intervention in the feasibility trial FAIR was valuable to support the maintenance of physical activity in the transition from a supervised exercise-based cardiac rehabilitation programme to everyday life on an individual basis. Participants experienced the intervention to hold their hands in changing behaviour and redefining themselves. Yet, there is an extended need for belonging and personal interactions in future interventions.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Aim: Long-term cognitive decline after out-of-hospital cardiac arrest (OHCA) is still poorly understood. This study describes long-term observer-reported cognitive decline among Danish OHCA survivors, including differences in years since the event, and investigates characteristics and self-reported outcomes associated with observer-reported cognitive decline., Methods: Adults who survived an OHCA from 2016 to 2019, and their relatives, completed the national DANish Cardiac Arrest Survivorship survey. Relatives completed the Informant Questionnaire on Cognitive Decline in the Elderly, Cardiac Arrest version (IQCODE-CA), the Hospital Anxiety and Depression Scale (HADS) and the World Health Organisation-Five Well-being index; and survivors completed the Two Simple Questions (everyday activities and mental recovery), the Modified Fatigue Impact Scale, HADS, and the Short World Health Organisation Disability Assessment Schedule 2.0. Potential associations between survivor characteristics and the IQCODE-CA were investigated using a multivariable logistic regression model. Self-reported outcomes among survivors and relatives, and the association with IQCODE-CA scores were investigated using separate logistic regression models., Results: Total median IQCODE-CA score was 3.04 (IQR: 3.00-3.27), with 47% having possible cognitive decline (score ≥ 3.04), consistent across time groups. Increasing age (OR 0.98, 95% CI: 0.97-0.99) and worse self-reported mental and physical outcomes for survivors and relatives, except 'everyday activities' were significantly associated with possible cognitive decline among survivors., Conclusions: Nearly half of OHCA survivors may suffer long-term cognitive decline. Worse self-reported mental and physical outcomes among survivors and their relatives are associated with potential cognitive decline emphasising the need for post-OHCA care to include systematic neurocognitive assessment, tailored support and effective rehabilitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the feasibility of a mobile health-supported intervention in patients with cardiovascular diseases after completion of a cardiac rehabilitation programme., Methods: The feasibility study was performed in two hospitals and one municipality in Region Zealand, Denmark. Eligible participants were ≥18 years old, participated in a supervised cardiac rehabilitation programme, had access to a mobile phone, and could walk 3 m independently. Participants received a 12-week intervention utilizing behaviour change techniques, consisting of action planning, text messages, and phone support. Feasibility was assessed using pre-defined progression criteria, which included recruitment (≥75%), retention (≥80%), accelerometer data completeness (≥80%), coordinator (phone support) time (≤30 min), the response rate on patient-reported outcomes (≥90%), adherence (≥75% respond to ≥75% of messages), and acceptability (≥75%). The secondary outcome of objective physical activity was assessed with accelerometers., Results: Ten women and 30 men with cardiovascular diseases aged 63.5 (±9.8 SD) participated. The progression criteria for retention (90%), accelerometer data completeness (83%), coordinator time (9.9 min), adherence (83%), and acceptability (82%) were at acceptable levels, exceptions were progression criteria for recruitment (35%) being below acceptable levels for recruitment, and response rate on patient-reported outcomes (75%). High satisfaction (92.6%) with the intervention was found. All objectively measured physical activity levels remained unchanged from baseline to follow-up. No serious adverse events related to the intervention were reported., Conclusion: Mobile health-supported maintenance of physical activity after cardiac rehabilitation completion was feasible, safe, and acceptable. Yet, changes to improve recruitment and response rate are needed before conducting a large-scale effect evaluation., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Aims: Rehabilitation targeting patients with cardiac conditions are evident and acknowledged in clinical guidelines. However, participation rates remain suboptimal, with only 50% of all patients with cardiac conditions participating in these programs across Europe. Considering the well-documented effects of rehabilitation, increasing the referral rate to cardiac rehabilitation would be desirable. This study aimed to evaluate the feasibility of a novel referral strategy that could potentially enhance enrollment in cardiac rehabilitation for patients with heart failure., Methods: This prospective feasibility study incorporating both quantitative and qualitative methods was conducted in an outpatient heart failure clinic and a municipal health care center. 106 patients with heart failure were referred to the heart failure clinic from September 2021 through July 2022. A 15-20 min face-to-face physiotherapy consultation was incorporated into usual care, evaluating patients' habitual and actual level of functioning, disability, and physical activity and assessing their potential need and motivation for cardiac rehabilitation. Three predefined quantitative feasibility outcomes: reach, referral rate, and data completeness were assessed. Additionally, semi-structured interviews explored acceptability among patients and health care professionals at the municipal health care center and the hospital. Finally, the potential effect was assessed based on the enrollment rate., Results: Physiotherapy consultations were offered to 86% of eligible patients; of these, 52% were referred to cardiac rehabilitation. Ninety-one percent data completeness was achieved. The intervention was well-accepted by patients and health care professionals. The enrollment rate reached 79%., Conclusion: The novel referral strategy proved feasible concerning reach and data completeness, although the referral rate suggested that further refinements are required before a full-scale trial. The novel referral strategy was well-accepted, and enrollment rate approached an acceptable level., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

In the early stage of the nematode Caenorhabditis elegans embryogenesis, the zygote divides asymmetrically into a symmetric fast lineage and an asymmetric slow lineage, producing 16 and 8 cells respectively almost at the same time, followed by the onset of gastrulation. It was recently reported that this cell division pattern is optimal for rapid cell proliferation. In this work, we compare the cell lineages of 9 nematode species, revealing that this pattern is conserved for >60 million years. It further suggests that such lineage design has an important functional role and it might speed up embryonic development in the nematode kingdom, not limited to C. elegans , and independent of the maternal-zygotic transition dynamics., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Introduction: Existing estimates of PD prevalence in Denmark are lower than those in the rest of Europe and are based on identification via single registries. Hence, are aim was to use a combined registry/self-report survey approach to identify people with PD and also investigate whether using different registry methods led to differences in the accuracy, completeness and characteristics of the identified cohorts., Methods: This study had a cross-sectional design using routinely collected health registry data to identify adults, ≥18 years of age and resident in Denmark, with PD from either the Danish National Patient (DNP) registry or Danish Prescription Medicines (DPM) registry. Those identified were asked to confirm their PD diagnosis using a national self-report survey., Results: 13,433 people were identified potentially as having PD via the DNP or DPM registry and sent a survey. Of these, 9094 responded (68 %) of which 85 % confirmed they had PD (n = 7763; 194/100,000; 95%CI:7650-7876). When adjusting for non-respondents, assuming an equal rate of confirmation in respondents and non-respondents, estimated Danish PD population was 11,467 (198.4/100,000; 95 % CI:197.2-199.6). Identification of people using those found in both registries led to 98 % confirming they had PD versus using one registry: DNP 93 % and DPM 88 %. No clear differences in sociodemographic characteristics were found between different registry identification methods., Conclusions: Estimated PD population in Denmark was significantly higher than previous Danish estimates and close to existing estimates in other European countries. The most accurate PD population was identified when including those found in both the DNP and DPM registries., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jette Theusen reports financial support was provided by the Danish Parkinson's Association., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: This study explored associations between digital health literacy and physical activity levels and assessed potential interactions of long-term health conditions., Methods: A cross-sectional survey was sent to 34,000 inhabitants in Region Zealand, Denmark. The survey included items on physical activity levels and three electronic Health Literacy Questionnaire (eHLQ) scales (1, 4, and 5). Associations were assessed by logistic regression and adjusted for confounders., Results: A total of 19,231 participated in the survey. Positive associations were found between higher digital health literacy and being active >30 min./week at moderate-to-vigorous intensity (eHLQ 1: OR 1.24, p < 0.001; eHLQ 4: OR 1.13, p = 0.012; eHLQ 5: OR 1.25, p < 0.001), compliance with the World Health Organization minimum recommendations for physical activity (eHLQ 1: OR 1.33 p < 0.001; eHLQ 4: OR 1.08 p = 0.025; eHLQ 5: OR 1.32, p < 0.001), and self-reported physical active (eHLQ 1: OR 1.50 p < 0.001; eHLQ 4: OR 1.24 p < 0.001; eHLQ 5: OR 1.54 p < 0.001), even when fully adjusted for covariates. No significant interaction was found for long-term health conditions. However, individuals with more long-term health conditions exhibited the lowest digital health literacy scores (9% to 19% scored <2.0)., Conclusion: A higher digital health literacy is positively associated with higher physical activity levels. This highlights the importance of screening and promoting digital health literacy in managing digital health and digital physical activity interventions. Future research should explore strategies and targeted interventions to enhance digital health literacy and improve health outcomes., (© The Author(s) 2024.)

Background: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer ., Methods: We reviewed the Memorial Sloan Kettering Cancer Center gastric, esophageal, and gastroesophageal junction cancer database. Associations between baseline characteristics and tumor and germline molecular alterations were compared between those with early-onset and average-onset esophagogastric cancer using Fisher exact tests and the Benjamini-Hochberg method for multiple-hypothesis correction., Results: We included 1123 patients with early-onset esophagogastric cancer (n = 219; median age = 43 years [range = 18-49 years]) and average-onset esophagogastric cancer (n = 904; median age = 67 years [range = 50-94 years]) treated between 2005 and 2018. The early-onset group had more women (39% vs 28%, P = .002). Patients with early-onset esophagogastric cancer were more likely to have a gastric primary site (64% vs 44%, P < .0001). The signet ring cell and/or diffuse type was 3 times more common in the early-onset esophagogastric cancer group (31% vs 9%, P < .0001). Early-onsite tumors were more frequently genomically stable (31% vs 18%, P = .0002) and unlikely to be microsatellite instability high (2% vs 7%, P = .003). After restricting to adenocarcinoma and signet ring cell and/or diffuse type carcinomas, we observed no difference in stage (P = .40) or overall survival from stage IV diagnosis (median = 22.7 vs 22.1 months, P = .78)., Conclusions: Our study supported a preponderance of gastric primary disease sites, signet ring histology, and genomically stable molecular subtypes in early-onset esophagogastric cancer. Our findings highlight the need for further research to define the underlying pathogenesis and strategies for early detection and prevention., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Signet ring cells (SRCs) may be observed in carcinomas from multiple primary sites. Elucidating unknown primaries from metastases with SRCs represents a diagnostic challenge. This study examined morphologic characteristics of adenocarcinomas with SRCs from stablished primary sites and described objective features, which can aid in identifying the site of origin., Methods: The series encompasses 257 cases of adenocarcinomas with SRCs from gastroesophageal junction (GEJ, n = 38), stomach (n = 48), pancreatobiliary system (n = 16), colorectum (n = 40), appendix (n = 32), breast (n = 41), and lung (n = 42). H&E sections were examined and scored using architectural and cytologic criteria. Morphometric analysis was performed using QuPath software., Results: Extracellular mucin was more abundant in GEJ, colorectal, and appendiceal carcinomas. Poorly cohesive morphology was the most frequent pattern in gastric and breast carcinomas. The cytoplasmic mucin/vacuole was predominantly clear and targetoid in breast carcinomas. Breast and gastric carcinomas showed the highest nuclear to cytoplasmic (N/C) ratio, whereas appendiceal carcinoma the lowest., Conclusion: Morphological evaluation (extracellular mucin, architectural patterns, and the nature of cytoplasmic mucin/vacuole) represents an important step to determine the cancer site of origin in adenocarcinomas with SRCs and guides further ancillary studies. Cytological morphometry may help further refine morphological criteria and facilitate the construction of digital-pathology algorithms., (© 2023 S. Karger AG, Basel.)

The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)