Pulmonary vein reconnection and repeat ablation characteristics following cryoballoon-compared to radiofrequency-based pulmonary vein isolation.

BACKGROUND: Despite advances in efficacy and safety of pulmonary vein isolation (PVI), atrial fibrillation (AF) recurrence after PVI remains common. PV-reconnection is the main finding during repeat PVI procedures performed to treat recurrent AF. OBJECTIVE: To analyze pulmonary vein (PV) reconnection patterns during repeat ablation procedures in a large cohort of consecutive patients undergoing radio frequency or cryoballoon-based PVI. METHODS: Retrospective analysis of PV-reconnection patterns and analysis of re-ablation strategies in consecutive index RF- and CB-based PVI and their respective re-ablation procedures during concomitant usage of both energy sources at a single high-volume center in Germany. RESULTS: A total of 610 first (06/2015-10/2022) and 133 s (01/2016-11/2022) repeat ablation procedures after 363 (60%) RF- and 247 (40%) CB-based index PVIs between 01/2015 and 12/2021 were analyzed. PV-reconnection was found in 509/610 (83%) patients at first and 74/133 (56%) patients at second repeat procedure. 465 of 968 (48%) initially via CB isolated PVs were reconnected at first re-ablation but 796 of 1422 initially RF-isolated PV (56%) were reconnected (OR: 0.73 [95% CI: 0.62-0.86]; p < .001). This was driven by fewer reconnections of the left PVs (LSPV: OR: 0.60 [95% CI: 0.42-0.86]; p = .005 and LSPV: 0.67 [0.47-0.95]; p = .026). PV-reconnection was more likely after longer, RF-based index PVI and in older females. Repeat procedures were shorter after CB-compared to after RF-PVI. CONCLUSIONS: Reconnection remains the most common reason for repeat AF ablation procedures after PVI. Our data suggest to preferentially use of the cryoballoon during index PVI, especially in older women.

Clinicopathological Factors as Predictors for Establishment of Patient Derived Head and Neck Squamous Cell Carcinoma Organoids.

INTRODUCTION: Patient derived organoids (PDOs) are 3D in vitro models and have shown to better reflect patient and tumor heterogeneity than conventional 2D cell lines. To utilize PDOs in clinical settings and trials for biomarker discovery or drug response evaluation, it is valuable to determine the best way to optimize sample selection for maximum PDO establishment. In this study, we assess patient, tumor and tissue sampling factors and correlate them with successful PDO establishment in a well-documented cohort of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Tumor and non-tumorous adjacent tissue samples were obtained from HNSCC patients during routine biopsy or resection procedures at the University Medical Center Utrecht. The tissue was subsequently processed to establish PDOs. The sample purity was determined as the presence of epithelial cells in the culture on the day of organoid isolation as visualized microscopically by the researcher. PDO establishment was recorded for all samples. Clinical data was obtained from the medical records and was correlated to PDO establishment and presence of epithelial cells. RESULTS: Organoids could be established in 133/250 (53.2%) primary tumor site tissues. HNSCC organoid establishment tended to be more successful if patients were younger than the median age of 68 years (74/123 (60.2%) vs. 59/127 (46.5%), p = 0.03). For a subset of samples, the presence of epithelial cells in the organoid culture on the day of organoid isolation was recorded in 112/149 (75.2%) of these samples. When cultures were selected for presence of epithelial cells, organoid establishment increased to 76.8% (86/112 samples). CONCLUSION: This study found a trend between age and successful organoid outgrowth in patients with HNSCC younger than 68 years and emphasizes the value of efficient sampling regarding PDO establishment.

Regional differences in predictive biomarker testing rates for patients with metastatic NSCLC in the Netherlands.

BACKGROUND: Predictive biomarker testing has a key role in the treatment decision-making for patients with non-small cell lung cancer (NSCLC) and is mandated by (inter)national guidelines. The aim of this study was to establish guideline-adherent biomarker testing rates in the Netherlands in 2019 and to examine associations of demographical, clinical, and environmental factors with guideline-adherent testing. METHODS: This study involved the integration of clinical data of the Netherlands Cancer Registry with pathology reports of the Dutch Nationwide Pathology Databank. Data extracted from these reports included sample type, diagnosis, and molecular testing status of predictive biomarkers. The study population comprised all patients diagnosed with metastatic non-squamous NSCLC in the Netherlands in 2019. RESULTS: In the cohort of 3877 patients with metastatic non-squamous NSCLC under investigation, overall molecular testing rates for non-fusion predictive biomarkers (EGFR, KRAS, BRAF, ERBB2, MET) ranged from 73.9 to 89.0 %, while molecular testing for fusion-drivers (ALK, ROS1, RET, NTRK) ranged from 12.6 % to 63.9 %. Guideline-adherent testing of EGFR, KRAS, and ALK was performed in 85.2 % of patients, with regional rates spanning from 76.0 % to 90.8 %. Demographical and clinical factors associated with guideline-adherent biomarker testing included lower age (OR = 1.05 per one year decrease; p < 0.001), female sex (OR = 1.36; p = 0.002), diagnosis of adenocarcinoma (OR = 2.48; p < 0.001), availability of histological tumor material (OR = 2.46; p < 0.001), and clinical stage of metastatic disease (p = 0.002). Other factors associated with guideline-adherent biomarker testing included diagnosis at academic center (OR = 1.87; p = 0.002) and patient's region of residence (p < 0∙001). CONCLUSION: Optimization of the chain-of-care of predictive biomarker testing in patients with NSCLC in the Netherlands is needed to provide adequate care for these patients.

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

p-mTOR, p-ERK and PTEN Expression in Tumor Biopsies and Organoids as Predictive Biomarkers for Patients with HPV Negative Head and Neck Cancer.

BACKGROUND: Survival rates of head and neck squamous cell carcinoma (HNSCC) have only marginally improved in the last decades. Hence there is a need for predictive biomarkers for long-time survival that can help to guide treatment decisions and might lead to the development of new therapies. The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is the most frequently altered pathway in HNSCC, genes are often mutated, amplificated and overexpressed causing aberrant signaling affecting cell growth and differentiation. Numerous genetic alterations of upstream and downstream factors have currently been clarified. However, their predictive value has yet to be established. Therefore we assess the predictive value of p-mTOR, p-ERK and PTEN expression. METHODS: Tissue microarrays (TMA's) of HPV-negative patients with oropharyngeal (n = 48), hypopharyngeal (n = 16) or laryngeal (n = 13) SCC, treated with primary chemoradiation (cisplatin/carboplatin/cetuximab and radiotherapy), were histologically stained for p-mTOR, PTEN and p-ERK. Expression was correlated to overall survival (OS), disease free survival (DFS) and locoregional control (LRC). Also p-mTOR was histologically stained in a separate cohort of HNSCC organoids (n = 8) and correlated to mTOR-inhibitor everolimus response. RESULTS: High p-mTOR expression correlated significantly with worse OS in multivariate analysis in the whole patient cohort [Hazar Ratio (HR) 1.06, 95%CI 1.01-1.11, p = 0.03] and in the cisplatin/carboplatin group with both worse OS (HR 1.09, 95%CI 1.02-1.16, p = 0.02) and DFS (HR 1.06, 95%CI 1.00-1.12, p = 0,04). p-ERK expression correlated significantly with DFS in univariate analysis in the whole patient cohort (HR 1.03, 95%CI 1.00-1.05, p = 0.04) and cisplatin/carboplatin group (HR 1.03, 95%CI 1.00-1.07, p = 0.04). PTEN-expression did not correlate with OS/DFS/LRC. Better organoid response to everolimus correlated significantly to higher p-mTOR expression (Rs = - 0.731, p = 0.04). CONCLUSIONS: High p-mTOR expression predicts and high p-ERK expression tends to predict worse treatment outcome in HPV negative HNSCC patients treated with chemoradiation, providing additional evidence that these markers are candidate prognostic biomarkers for survival in this patient population. Also this study shows that the use of HNSCC organoids for biomarker research has potential. The role of PTEN expression as prognostic biomarker remains unclear, as consistent evidence on its prognostic and predictive value is lacking.

The need for longitudinal data on the value of fertility treatment for infertile patients' quality of life: A review and pilot study.

Infertility threatens the life goal of parenthood and, hence, quality of life (QoL) of (wo)men, but the fertility clinic trajectory might be burdensome. This review of longitudinal studies and pilot longitudinal study examines the impact of the pre-in vitro fertilization (IVF) fertility clinic trajectory on patient-reported outcome measures (PROMs) for emotional well-being, including QoL. A publication found that the diagnostic workup decreases men's infertility-specific distress while publications disagree whether it decreases (wo)men's anxious and depressive reactions. Intrauterine insemination (IUI) was found to increase (wo)men's depressive reactions. Publications on infertility-specific, health-related, and overall QoL were missing. The pilot indicated that (wo)men's overall QoL is not affected by the diagnostic workup but is decreased by the time of the third IUI. Longitudinal studies on the impact of starting the fertility clinic trajectory on PROMs are needed as they are essential for patient-centered clinical decision-making and patient-centered policy-level decision-making.

Prognostic influence of mechanical cardiopulmonary resuscitation on survival in patients with out-of-hospital cardiac arrest undergoing ECPR on VA-ECMO.

Introduction: The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in extracorporeal cardiopulmonary resuscitation (ECPR) in selected patients after out-of-hospital cardiac arrest (OHCA) is an established method if return of spontaneous circulation cannot be achieved. Automated chest compression devices (ACCD) facilitate transportation of patients under ongoing CPR and might improve outcome. We thus sought to evaluate prognostic influence of mechanical CPR using ACCD in patients presenting with OHCA treated with ECPR including VA-ECMO. Methods: We retrospectively analyzed data of 171 consecutive patients treated for OHCA using ECPR in our cardiac arrest center from the years 2016 to 2022. A Cox proportional hazards model was used to identify characteristics related with survival. Results: Of the 171 analyzed patients (84% male, mean age 56 years), 12% survived the initial hospitalization with favorable neurological outcome. The primary reason for OHCA was an acute coronary event (72%) followed by primary arrhythmia (9%) and non-ischemic cardiogenic shock (6.7%). In most cases, the collapse was witnessed (83%) and bystander CPR was performed (83%). The median time from collapse to VA-ECMO was 81 min (Q1: 69 min, Q3: 98 min). No survival benefit was seen for patients resuscitated using ACCD. Patients in whom an ACCD was used presented with overall longer times from collapse to ECMO than those who were resuscitated manually [83 min (Q1: 70 min, Q3: 98 min) vs. 69 min (Q1: 57 min, Q3: 84 min), p = 0.004]. Conclusion: No overall survival benefit of the use of ACCD before ECPR is established was found, possibly due to longer overall CPR duration. This may arguably be because of the limited availability of ACCD in pre-clinical paramedic service at the time of observation. Increasing the availability of these devices might thus improve treatment of OHCA, presumably by providing efficient CPR during transportation and transfer.

Gender disparities in patients undergoing extracorporeal cardiopulmonary resuscitation.

Introduction: The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in extracorporeal cardiopulmonary resuscitation (eCPR) has emerged as a treatment option for selected patients who are experiencing refractory cardiac arrest (CA). In the light of increasing availability, the analyses of outcome-relevant predisposing characteristics are of growing importance. We evaluated the prognostic influence of gender in patients presenting with out-of-hospital cardiac arrest (OHCA) treated with eCPR. Methods: We retrospectively analysed the data of 377 consecutive patients treated for OHCA using eCPR in our cardiac arrest centre from January 2016 to December 2022. The primary outcome was defined as the survival of patients until they were discharged from the hospital, with a favourable neurological outcome [cerebral performance category (CPC) score of ≤2]. Statistical analyses were performed using baseline comparison, survival analysis, and multivariable analyses. Results: Out of the 377 patients included in the study, 69 (21%) were female. Female patients showed a lower prevalence rate of pre-existing coronary artery disease (48% vs. 75%, p < 0.001) and cardiomyopathy (17% vs. 34%, p = 0.01) compared with the male patients, while the mean age and prevalence rate of other cardiovascular risk factors were balanced. The primary reason for CA differed significantly (female: coronary event 45%, pulmonary embolism 23%, cardiogenic shock 17%; male: coronary event 70%, primary arrhythmia 10%, cardiogenic shock 10%; p = 0.001). The prevalence rate of witnessed collapse (97% vs. 86%; p = 0.016) and performance of bystander CPR (94% vs. 85%; p = 0.065) was higher in female patients. The mean time from collapse to the initiation of eCPR did not differ between the two groups (77 ± 39 min vs. 80 ± 37 min; p = 0.61). Overall, female patients showed a higher percentage of neurologically favourable survival (23% vs. 12%; p = 0.027) despite a higher prevalence of procedure-associated bleeding complications (33% vs. 16%, p = 0.002). The multivariable analysis identified a shorter total CPR duration (p = 0.001) and performance of bystander CPR (p = 0.03) to be associated with superior neurological outcomes. The bivariate analysis showed relevant interactions between gender and body mass index (BMI). Conclusion: Our analysis suggests a significant survival benefit for female patients who obtain eCPR, possibly driven by a higher prevalence of witnessed collapse and bystander CPR. Interestingly, the impact of patient age and BMI on neurologically favourable outcome was higher in female patients than in male patients, warranting further investigation.

Clinical evaluation of a deep learning model for segmentation of target volumes in breast cancer radiotherapy.

PURPOSE/OBJECTIVE(S): Precise segmentation of clinical target volumes (CTV) in breast cancer is indispensable for state-of-the art radiotherapy. Despite international guidelines, significant intra- and interobserver variability exists, negatively impacting treatment outcomes. The aim of this study is to evaluate the performance and efficiency of segmentation of CTVs in planning CT images of breast cancer patients using a 3D convolutional neural network (CNN) compared to the manual process. MATERIALS/METHODS: An expert radiation oncologist (RO) segmented all CTVs separately according to international guidelines in 150 breast cancer patients. This data was used to create, train and validate a 3D CNN. The network's performance was additionally evaluated in a test set of 20 patients. Primary endpoints are quantitative and qualitative analysis of the segmentation data generated by the CNN for each level specifically as well as for the total PTV to be irradiated. The secondary endpoint is the evaluation of time efficiency. RESULTS: In the test set, segmentation performance was best for the contralateral breast and the breast CTV and worst for Rotter's space and the internal mammary nodal (IMN) level. Analysis of impact on PTV resulted in non-significant over-segmentation of the primary PTV and significant under-segmentation of the nodal PTV, resulting in slight variations of overlap with OARs. Guideline consistency improved from 77.14% to 90.71% in favor of CNN segmentation while saving on average 24 minutes per patient with a median time of 35 minutes for pure manual segmentation. CONCLUSION: 3D CNN based delineation for breast cancer radiotherapy is feasible and performant, as scored by quantitative and qualitative metrics.

How did general practices organize care during the COVID-19 pandemic: the protocol of the cross-sectional PRICOV-19 study in 38 countries.

BACKGROUND: General practitioners (GPs) play a crucial role in the fight against the COVID-19 pandemic as the first point of contact for possibly infected patients and are responsible for short and long-term follow-up care of the majority of COVID-19 patients. Nonetheless, they experience many barriers to fulfilling this role. The PRICOV-19 study investigates how GP practices in 38 countries are organized during the COVID-19 pandemic to guarantee safe, effective, patient-centered, and equitable care. Also, the shift in roles and tasks and the wellbeing of staff members is researched. Finally, PRICOV-19 aims to study the association with practice- and health care system characteristics. It is expected that both characteristics of the GP practice and health care system features are associated with how GP practices can cope with these challenges. This paper describes the protocol of the study. METHODS: Using a cross-sectional design, data are collected through an online questionnaire sent to GP practices in 37 European countries and Israel. The questionnaire is developed in multiple phases, including a pilot study in Belgium. The final version includes 53 items divided into six sections: patient flow (including appointments, triage, and management for routine care); infection prevention; information processing; communication; collaboration and self-care; and practice and participant characteristics. In the countries where data collection is already finished, between 13 and 636 GP practices per country participated in the study. Questionnaire data are linked with OECD and HSMR data regarding national policy responses to the pandemic and analyzed using multilevel models considering the system- and practice-level. DISCUSSION: To the best of our knowledge, the PRICOV-19 study is the largest and most comprehensive study that examines how GP practices function during the COVID-19 pandemic. Its results can significantly contribute to better preparedness of primary health care systems across Europe for future major outbreaks of infectious diseases.

Open lateral femoral condyle fracture concomitant with a vertical patella fracture in an adolescent: A case report.

We present the rare case of an open femoral condyle fracture (Gustilla IIIA) combined with a vertical patella fracture due to sharp injury after a traffic collision in a 17-year-old female. During subsequent operation, a locking compression plate was used for definitive fixation of the distal femur and the patella was reduced and fixated with two screws. Four months after surgery, the patient had practically full range of motion again and no secondary complications occurred. On control X-ray, there was consolidation of the fracture.

Interobserver variability in organ at risk delineation in head and neck cancer.

BACKGROUND: In radiotherapy inaccuracy in organ at risk (OAR) delineation can impact treatment plan optimisation and treatment plan evaluation. Brouwer et al. showed significant interobserver variability (IOV) in OAR delineation in head and neck cancer (HNC) and published international consensus guidelines (ICG) for OAR delineation in 2015. The aim of our study was to evaluate IOV in the presence of these guidelines. METHODS: HNC radiation oncologists (RO) from each Belgian radiotherapy centre were invited to complete a survey and submit contours for 5 HNC cases. Reference contours (OARref) were obtained by a clinically validated artificial intelligence-tool trained using ICG. Dice similarity coefficients (DSC), mean surface distance (MSD) and 95% Hausdorff distances (HD95) were used for comparison. RESULTS: Fourteen of twenty-two RO (64%) completed the survey and submitted delineations. Thirteen (93%) confirmed the use of delineation guidelines, of which six (43%) used the ICG. The OARs whose delineations agreed best with the OARref were mandible [median DSC 0.9, range (0.8-0.9); median MSD 1.1 mm, range (0.8-8.3), median HD95 3.4 mm, range (1.5-38.7)], brainstem [median DSC 0.9 (0.6-0.9); median MSD 1.5 mm (1.1-4.0), median HD95 4.0 mm (2.3-15.0)], submandibular glands [median DSC 0.8 (0.5-0.9); median MSD 1.2 mm (0.9-2.5), median HD95 3.1 mm (1.8-12.2)] and parotids [median DSC 0.9 (0.6-0.9); median MSD 1.9 mm (1.2-4.2), median HD95 5.1 mm (3.1-19.2)]. Oral cavity, cochleas, PCMs, supraglottic larynx and glottic area showed more variation. RO who used the consensus guidelines showed significantly less IOV (p = 0.008). CONCLUSIONS: Although ICG for delineation of OARs in HNC exist, they are only implemented by about half of RO participating in this study, which partly explains the delineation variability. However, this study highlights that guidelines alone do not suffice to eliminate IOV and that more effort needs to be done to accomplish further treatment standardisation, for example with artificial intelligence.

Predictive Value of EGFR-PI3K-AKT-mTOR-Pathway Inhibitor Biomarkers for Head and Neck Squamous Cell Carcinoma: A Systematic Review.

BACKGROUND: Understanding molecular pathogenesis of head and neck squamous cell carcinomas (HNSCC) has considerably improved in the last decades. As a result, novel therapeutic strategies have evolved, amongst which are epidermal growth factor receptor (EGFR)-targeted therapies. With the exception of cetuximab, targeted therapies for HNSCC have not yet been introduced into clinical practice. One important aspect of new treatment regimes in clinical practice is presence of robust biomarkers predictive for therapy response. METHODS: We performed a systematic search in PubMed, Embase and the Cochrane library. Articles were included if they investigated a biomarker for targeted therapy in the EGFR-PI3K-AKT-mTOR-pathway. RESULTS: Of 83 included articles, 52 were preclinical and 33 were clinical studies (two studies contained both a preclinical and a clinical part). We classified EGFR pathway inhibitor types and investigated the type of biomarker (biomarker on epigenetic, DNA, mRNA or protein level). CONCLUSION: Several EGFR-PI3K-AKT-mTOR-pathway inhibitor biomarkers have been researched for HNSCC but few of the investigated biomarkers have been adequately confirmed in clinical trials. A more systematic approach is needed to discover proper biomarkers as stratifying patients is essential to prevent unnecessary costs and side effects.

[Short version of the 2nd edition of the German-Austrian S3 guidelines "Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment"]. / Kurzversion der 2. Auflage der deutsch-österreichischen S3-Leitlinie "Infarkt-bedingter Kardiogener Schock ­ Diagnose, Monitoring und Therapie".

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.

Randomized controlled trial of a group intervention combining self-hypnosis and self-care: secondary results on self-esteem, emotional distress and regulation, and mindfulness in post-treatment cancer patients.

PURPOSE: Cancer patients often report low self-esteem and high emotional distress. Two factors seem particularly linked to these symptoms: emotion regulation strategies and mindfulness. The interest of hypnosis and self-care to relieve these symptoms is not well documented. Our randomized controlled trial aimed at assessing the effect of a group intervention combining self-hypnosis and self-care on self-esteem, emotional distress, emotion regulation, and mindfulness abilities of post-treatment cancer patients, as well as investigating the links between these variables. METHODS: One hundred and four patients who had suffered from cancer were randomized into the intervention group (N = 52) and the wait-list control group (N = 52). They had to answer questionnaires before (T1) and after the intervention (T2). Nine men were excluded from the analyses, leading to a final sample of 95 women with cancer. Group-by-time changes were assessed with MANOVA, and associations with self-esteem and emotional distress were investigated with hierarchical linear regression models. RESULTS: Participants in the intervention group (mean age = 51.65; SD = 12.54) reported better self-esteem, lower emotional distress, a decreased use of maladaptive emotion regulation strategies, and more mindfulness abilities after the intervention, compared to the WLCG. This increase in mindfulness explained 33% of the improvement of self-esteem and 41.6% of the decrease of emotional distress in the intervention group. Self-esteem and emotional distress also predicted each other. CONCLUSION: Our study showed the efficacy of our hypnosis-based intervention to improve all the investigated variables. Mindfulness predicted the improvement of self-esteem and emotional distress. The primary impact of our intervention on mindfulness abilities seems to explain, at least in part, its efficacy. Registration: ClinicalTrials.gov (NCT03144154). Retrospectively registered on the 1st of May, 2017.

Deep learning for elective neck delineation: More consistent and time efficient.

BACKGROUND/PURPOSE: Delineation of the lymph node levels of the neck for irradiation of the elective clinical target volume in head and neck cancer (HNC) patients is time consuming and prone to interobserver variability (IOV), although international consensus guidelines exist. The aim of this study was to develop and validate a 3D convolutional neural network (CNN) for semi-automated delineation of all nodal neck levels, focussing on delineation accuracy, efficiency and consistency compared to manual delineation. MATERIAL/METHODS: The CNN was trained on a clinical dataset of 69 HNC patients. For validation, 17 lymph node levels were manually delineated in 16 new patients by two observers, independently, using international consensus guidelines. Automated delineations were generated by applying the CNN and were subsequently corrected by both observers separately as needed for clinical acceptance. Both delineations were performed two weeks apart and blinded to each other. IOV was quantified using Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD). To assess automated delineation accuracy, agreement between automated and corrected delineations were evaluated using the same measures. To assess efficiency, the time taken for manual and corrected delineations were compared. In a second step, only the clinically relevant neck levels were selected and delineated, once again manually and by applying and correcting the network. RESULTS: When all lymph node levels were delineated, time taken for correcting automated delineations compared to manual delineations was significantly shorter for both observers (mean: 35 vs 52 min, p < 10-5). Based on DSC, automated delineation agreed best with corrected delineation for lymph node levels Ib, II-IVa, VIa, VIb, VIIa, VIIb (DSC >85%). Manual corrections necessary for clinical acceptance were 1.4 mm MSD on average and were especially low (<1mm) for levels II-IVa, VIa, VIIa and VIIb. IOV was significantly smaller with automated compared to manual delineations (MSD: 1.4 mm vs 2.5 mm, p < 10-11). When delineating only the clinically relevant neck levels, the correction time was also significantly shorter (mean: 8 vs 15 min, p < 10-5). Based on DSC, automated delineation agreed very well with corrected delineation (DSC > 87%). Manual corrections necessary for clinical acceptance were 1.3 mm MSD on average. IOV was significantly smaller with automated compared to manual delineations (MSD: 0.8 mm vs 2.3 mm, p < 10-3). CONCLUSION: The CNN developed for automated delineation of the elective lymph node levels in the neck in HNC was shown to be more efficient and consistent compared to manual delineation, which justifies its implementation in clinical practice.

[Therapeutic management of nonvalvular atrial fibrillation]. / Therapeutisches Management des nichtvalvulären Vorhofflimmerns.

Atrial fibrillation (AF) is the most frequent persistent cardiac arrhythmia and is associated with an increased mortality. Therefore, an effective differential treatment of patients is mandatory. After a risk stratification oral anticoagulation (OAC) should be initiated depending on the individual stroke risk of each patient. Alternatively, in the presence of contraindications for OAC and an increased risk for bleeding and/or stroke, the implantation of a left atrial appendage closure device can be considered. Symptomatic patients should undergo a rhythm control strategy if possible. Based on the risk-benefit considerations, catheter ablation (CA) of AF plays an increasingly important role in establishing long-term medicinal rhythm control. A pulmonary vein isolation can lead to freedom from AF for 1 year in 70-80% of patients with paroxysmal AF (and approximately 50% in persistent AF). So far, a survival advantage of CA could only be shown in patients with heart failure, so that in most cases this is only a symptomatic treatment for improvement in the quality of life.

Presence of a 34-gene signature is a favorable prognostic marker in squamous non-small cell lung carcinoma.

BACKGROUND: The tumor immune microenvironment is a heterogeneous entity. Gene expression analysis allows us to perform comprehensive immunoprofiling and may assist in dissecting the different components of the immune infiltrate. As gene expression analysis also provides information regarding tumor cells, differences in interactions between the immune system and specific tumor characteristics can also be explored. This study aims to gain further insights in the composition of the tumor immune infiltrate and to correlate these components to histology and overall survival in non-small cell lung cancer (NSCLC). METHODS: Archival tissues from 530 early stage, resected NSCLC patients with annotated tumor and patient characteristics were analyzed using the NanoString nCounter Analysis system. RESULTS: Unsupervised clustering of the samples was mainly driven by the overall level of inflammation, which was not correlated with survival in this patient set. Adenocarcinoma (AD) showed a significantly higher degree of immune infiltration compared to squamous cell carcinoma (SCC). A 34-gene signature, which did not correlate with the overall level of immune infiltration, was identified and showed an OS benefit in SCC. Strikingly, this benefit was not observed in AD. This difference in OS in SCC specifically was confirmed in two independent NSCLC cohorts. The highest correlation between expression of the 34-gene signature and specific immune cell populations was observed for NK cells, but although a plausible mechanism for NK cell intervention in tumor growth could be established in SCC over AD, this could not be translated back to immunohistochemistry, which showed that NK cell infiltration is scarce irrespective of histology. CONCLUSIONS: These findings suggest that the ability of immune cell infiltration and the interaction between tumor and immune cells may be different between AD and SCC histology and that a subgroup of SCC tumors seems more susceptible to Natural Killer cell recognition and killing, whereas this may not occur in AD tumors. A highly sensitive technique like NanoString was able to detect this subgroup based on a 34-gene signature, but further research will be needed to assist in explaining the biological rationale of such low-level expression signatures.