Precise Prediction of Long-Term Urinary Incontinence after Robot-Assisted Laparoscopic Radical Prostatectomy by Readily Accessible "Everyday" Diagnostics during Post-Surgical Hospitalization.

Aim and Objectives: We aimed to test the predictive value of readily accessible and easily performed post-surgical "bedside tests" on their validity of long-term urinary incontinence (UI) (≥12 months) in patients following robot-assisted laparoscopic radical prostatectomy (RALP). Material and Methods: Patients undergoing RALP between July 2020 and March 2021 were prospectively included and subdivided into two groups based on their pad usage after 12 months (0 vs. ≥1 pad). After catheter removal, patients performed a 1 h pad test, documented the need for pad change in a micturition protocol and received post-voiding residual urine volume ultrasound. Univariate and multivariable analyses were used to demonstrate the predictive value of easily accessible tests applied after catheter removal for UI following RALP. Results: Of 109 patients, 47 (43%) had to use at least one pad (vs. 62 (57%) zero pads) after 12 months. Univariate testing showed a significant difference in urine loss between both groups evaluated by the 1 h pad test performed within 24 h after catheter removal (70% < 10 mL, vs. 30% ≥ 10 mL, p = 0.004) and in the need for pad change within the first 24 h after catheter removal (14% dry pads vs. 86% wet pads, p = 0.003). In multivariable analyses, the combination of both tests (synoptical incontinence score) could be confirmed as an independent predictor for UI after 12 months (p = 0.011). Conclusions: Readily accessible "everyday" diagnostics (pad test/change of pads after catheter removal) following RALP seem to be associated with a higher rate of long-term UI. This finding is crucial since patients with a potentially higher need for patient education and counselling can be identified using these readily accessible tests. This could lead to a higher patient satisfaction and improved outcomes.

Patient-Relevant Costs for Organ Preservation versus Radical Resection in Locally Advanced Rectal Cancer.

Total neoadjuvant therapy (TNT) is an evolving treatment schedule for locally advanced rectal cancer (LARC), allowing for organ preservation in a relevant number of patients in the case of complete response. Patients who undergo this so-called "watch and wait" approach are likely to benefit regarding their quality of life (QoL), especially if definitive ostomy could be avoided. In this work, we performed the first cost-effectiveness analysis from the patient perspective to compare costs for TNT with radical resection after neoadjuvant chemoradiation (CRT) in the German health care system. Individual costs for patients insured with a statutory health insurance were calculated with a Markov microsimulation. A subgroup analysis from the prospective "FinTox" trial was used to calibrate the model's parameters. We found that TNT was less expensive (-1540 EUR) and simultaneously resulted in a better QoL (+0.64 QALYs) during treatment and 5-year follow-up. The average cost for patients under TNT was 4711 EUR per year, which was equivalent to 3.2% of the net household income. CRT followed by resection resulted in higher overall costs for ostomy care, medication and greater loss of earnings. Overall, TNT appeared to be more efficacious and cost-effective from a patient's point of view in the German health care system.

Intraoperative application of mixed and augmented reality for digital surgery: a systematic review of ethical issues.

Introduction: Head-mounted displays (HMDs) that superimpose holograms onto patients are of particular surgical interest as they are believed to dramatically change surgical procedures by including safety warning and allowing real-time offsite consultations. Although there are promising benefits of mixed and augmented reality (MR/AR) technologies in surgery, they also raise new ethical concerns. The aim of this systematic review is to determine the full spectrum of ethical issues that is raised for surgeons in the intraoperative application of MR/AR technology. Methods: Five bibliographic databases were searched for publications on the use of MR/AR, HMDs and other devices, their intraoperative application in surgery, and ethical issues. We applied qualitative content analysis to the n = 50 articles included. Firstly, we coded the material with deductive categories derived from ethical frameworks for surgical innovations, complications and research. Secondly, clinical aspects with ethical relevance were inductively coded as ethical issues within the main categories. Thirdly, we pooled the ethical issues into themes and sub-themes. We report our findings according to the reporting guideline RESERVE. Results: We found n = 143 ethical issues across ten main themes, namely patient-physician relationship, informed consent, professionalism, research and innovation, legal and regulatory issues, functioning equipment and optimal operating conditions, allocation of resources, minimizing harm, good communication skills and the ability to exercise sound judgement. The five most prevalent ethical issues are "Need for continuous research and innovation", "Ensuring improvement of the learning curve", "MR/AR enables new maneuvers for surgeons", "Ensuring improvement of comfort, ergonomics, and usability of devices," and "Not withholding MR/AR if it performs better". Conclusions: Recognizing the evidence-based limitations of the intraoperative MR/AR application is of paramount importance to avoid ethical issues, but clinical trials in surgery pose particular ethical risks for patients. Regarding the digital surgeon, long-term impact on human workforce, potentially harmful "negative training," i.e., acquiring inappropriate behaviors, and the fear of surveillance need further attention. MR/AR technologies offer not only challenges but significant advantages, promoting a more equitable distribution of surgical expertise and optimizing healthcare. Aligned with the core principle of social justice, these technologies enable surgeons to collaborate globally, improving training conditions and addressing enduring global healthcare inequalities.

Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Multidisciplinary survey on use of feeding tubes in head and neck cancer patients undergoing chemoradiotherapy in Germany-the SUFEETUBE project.

BACKGROUND AND OBJECTIVE: Data on enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy vary considerably between German institutions. This survey aims to investigate the management of feeding tubes in an interdisciplinary context across Germany. MATERIALS AND METHODS: Between December 2022 and May 2023, 70 participants (42 radiation oncologists, 12 medical oncologists, 14 head and neck surgeons, and 2 physicians covering several specialties) responded to our web-based survey. In addition to the type of institution (university hospital, private practice, etc.), their age, and professional experience (in years), participants were asked several questions on the indication and institutional policy for tube placement and management (prophylactic/reactive nasogastric or gastrostomy tube). All questions were mandatory single- or multiple-choice questions, while additional comments were possible by email. RESULTS: Most participants were employed at a university hospital (n = 52; 74.3%) and came from a radiation oncology background (n = 42; 60%). Fifty-four contributors (77.1%) reported that no nutritional risk screening prior to chemoradiotherapy was routinely performed, and 71.4% (n = 50) stated that no standardized protocol was used at the institution to set the indication for tube placement. Generally, policies and methods of tube feeding vary considerably between the individual institutions and specialties. However, the majority (n = 56, 80%) recommended a prophylactic percutaneous enteral gastrostomy (PEG) tube to their patients before chemoradiotherapy. Still, there was no consistent trend regarding the approach for reactive tube feeding. CONCLUSION: The policies and methods of tube feeding vary considerably between the individual institutions and specialties in Germany. In the era of individualized medicine, uniform protocols are difficult to establish. However, a baseline nutritional risk screening could simplify decision-making in clinical practice.

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.

Satisfaction with radiotherapy care among cancer patients treated in Germany-secondary analysis of a large multicenter study.

PURPOSE: Patient satisfaction with healthcare has been linked to clinical outcomes and regulatory agencies demand its regular assessment. Therefore, we aimed to investigate patient satisfaction with radiotherapy care and its determinants. METHODS: This is a secondary analysis of a multicenter prospective cross-sectional study. Eligible cancer patients anonymously completed questionnaires at the end of a course of radiotherapy. The outcome variable was overall patient satisfaction with radiotherapy care measured with a 10-point Likert scaled single-item. Given patient satisfaction was defined for patients scoring ≥ 8 points. Determinants of given patient satisfaction were assessed by univariable and multivariable analyses. A p-value < 0.05 was considered statistically significant. RESULTS: Out of 2341 eligible patients, 1075 participated (participation rate 46%). Data on patient satisfaction was provided by 1054 patients. There was a right-skewed distribution towards more patient satisfaction (mean = 8.8; SD = 1.68). Given patient satisfaction was reported by 85% (899/1054) of the patients. Univariable analyses revealed significant associations of lower patient satisfaction with tumor entity (rectal cancer), concomitant chemotherapy, inpatient care, treating center, lower income, higher costs, and lower quality of life. Rectal cancer as tumor entity, treating center, and higher quality of life remained significant determinants of patient satisfaction in a multivariable logistic regression. CONCLUSION: Overall patient satisfaction with radiotherapy care was high across 11 centers in Germany. Determinants of patient satisfaction were tumor entity, treating center, and quality of life. Although these data are exploratory, they may inform other centers and future efforts to maintain high levels of patient satisfaction with radiotherapy care.

App-Controlled Treatment Monitoring and Support for Patients With Head and Neck Cancer Undergoing Radiotherapy: Results From a Prospective Randomized Controlled Trial.

BACKGROUND: Head and neck cancers (HNCs) are very common malignancies, and treatment often requires multimodal approaches, including radiotherapy and chemotherapy. Patients with HNC often display a high symptom burden, both due to the disease itself and the adverse effects of the multimodal therapy. Close telemonitoring of symptoms and quality of life during the course of treatment may help to identify those patients requiring early medical support. OBJECTIVE: The App-Controlled Treatment Monitoring and Support for Patients With Head and Neck Cancer (APCOT) trial aimed to investigate the feasibility of integrating electronic patient-reported outcomes (ePROs) in the treatment surveillance pathway of patients with HNC during the course of their radiotherapy. Additionally, the influence of app-based ePRO monitoring on global and disease-specific quality of life and patient satisfaction with treatment was assessed. METHODS: Patients undergoing radiotherapy for histologically proven HNCs at the Department of Radiation Oncology, University Medical Center Freiburg, Germany, were enrolled in this trial and monitored by weekly physician appointments. Patients were randomized between additional ePRO monitoring on each treatment day or standard-of-care monitoring. Feasibility of ePRO monitoring was defined as ≥80% of enrolled patients answering ≥80% of their daily app-based questions. Quality of life and patient satisfaction were assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30), the head and neck cancer module (H&N35), and the validated Patient Satisfaction Questionnaire Short Form (PSQ-18) at the completion of treatment and compared between trial arms. RESULTS: A total of 100 patients were enrolled in this trial, and 93 patients were evaluable. All patients (100%) in the experimental arm answered ≥80% of the ePRO questions during treatment, reaching the predefined threshold for the feasibility of ePRO monitoring (P<.001 in the binomial test). No clinical or patient-specific factor was found to influence feasibility. Global health and most domains of the general quality of life were comparable between trial arms, but an increased HNC-specific symptom burden was reported by patients undergoing ePRO surveillance. ePRO monitoring resulted in improved patient satisfaction regarding interpersonal manners (P=.01), financial aspects (P=.01), and time spent with a doctor (P=.01). CONCLUSIONS: This trial demonstrated the feasibility of incorporating daily app-based ePRO surveillance for patients with HNC undergoing radiotherapy. Our data, for the first time, demonstrate that telemonitoring in this setting led to increased reporting of HNC-specific symptom burden and significantly improved several domains of patient satisfaction. Further analyses are needed to assess whether our findings hold true outside the context of a clinical trial. TRIAL REGISTRATION: German Clinical Trials Register DRKS00020491; https://drks.de/search/en/trial/DRKS00020491.

Altered brain network organization in adults with Asperger's syndrome: decreased connectome transitivity and assortativity with increased global efficiency.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that persists into adulthood with both social and cognitive disturbances. Asperger's syndrome (AS) was a distinguished subcategory of autism in the DSM-IV-TR defined by specific symptoms including difficulties in social interactions, inflexible thinking patterns, and repetitive behaviour without any delay in language or cognitive development. Studying the functional brain organization of individuals with these specific symptoms may help to better understand Autism spectrum symptoms. Methods: The aim of this study is therefore to investigate functional connectivity as well as functional network organization characteristics using graph-theory measures of the whole brain in male adults with AS compared to healthy controls (HC) (AS: n = 15, age range 21-55 (mean ± sd: 39.5 ± 11.6), HC: n = 15, age range 22-57 [mean ± sd: 33.5 ± 8.5]). Results: No significant differences were found when comparing the region-by-region connectivity at the whole-brain level between the AS group and HC. However, measures of "transitivity," which reflect local information processing and functional segregation, and "assortativity," indicating network resilience, were reduced in the AS group compared to HC. On the other hand, global efficiency, which represents the overall effectiveness and speed of information transfer across the entire brain network, was increased in the AS group. Discussion: Our findings suggest that individuals with AS may have alterations in the organization and functioning of brain networks, which could contribute to the distinctive cognitive and behavioural features associated with this condition. We suggest further research to explore the association between these altered functional patterns in brain networks and specific behavioral traits observed in individuals with AS, which could provide valuable insights into the underlying mechanisms of its symptomatology.

Association Between Recanalization Attempts and Functional Outcome After Thrombectomy for Large Ischemic Stroke.

BACKGROUND: Recently, 3 randomized controlled trials provided high-level evidence that patients with large ischemic stroke achieved better functional outcomes after endovascular therapy than with medical care alone. We aimed to investigate whether the clinical benefit of endovascular therapy is associated with the number of recanalization attempts in extensive baseline infarction. METHODS: This retrospective multicenter study enrolled patients from the German Stroke Registry who underwent endovascular therapy for anterior circulation large vessel occlusion between 2015 and 2021. Large ischemic stroke was defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5. The study cohort was divided into patients with unsuccessful reperfusion (Thrombolysis in Cerebral Infarction score, 0-2a) and successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b/3) at attempts 1, 2, 3, or ≥4. The primary outcome was favorable functional outcome defined as modified Rankin Scale score of 0 to 3 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage after 24 hours and death within 90 days. Multivariable logistic regression was used to identify independent determinants of primary and secondary outcomes. RESULTS: A total of 348 patients met the inclusion criteria. Successful reperfusion was observed in 83.3% and favorable functional outcomes in 36.2%. Successful reperfusion at attempts 1 (adjusted odds ratio, 5.97 [95% CI, 1.71-24.43]; P=0.008) and 2 (adjusted odds ratio, 6.32 [95% CI, 1.73-26.92]; P=0.008) increased the odds of favorable functional outcome, whereas success at attempts 3 or ≥4 did not. Patients with >2 attempts showed higher rates of symptomatic intracranial hemorrhage (12.8% versus 6.5%; P=0.046). Successful reperfusion at any attempt lowered the odds of death compared with unsuccessful reperfusion. CONCLUSIONS: In patients with large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5, the clinical benefit of endovascular therapy was linked to the number of recanalization attempts required for successful reperfusion. Our findings encourage to perform at least 2 recanalization attempts to seek for successful reperfusion in large ischemic strokes, while >2 attempts should follow a careful risk-benefit assessment in these highly affected patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Psychosocial distress in cancer patients undergoing radiotherapy: a prospective national cohort of 1042 patients in Germany.

PURPOSE: Psychosocial distress is common among cancer patients in general, but those undergoing radiotherapy may face specific challenges. Therefore, we investigated the prevalence and risk factors for distress in a large national cohort. METHODS: We performed a secondary analysis of a multicenter prospective cross-sectional study which surveyed cancer patients at the end of a course of radiotherapy using a patient-reported questionnaire. Distress was measured with the distress thermometer (DT), using a cut-off of ≥ 5 points for clinically significant distress. Univariate analyses and multivariate multiple regression were used to assess associations of distress with patient characteristics. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: Out of 2341 potentially eligible patients, 1075 participated in the study, of which 1042 completed the DT. The median age was 65 years and 49% (511/1042) of patients were female. The mean DT score was 5.2 (SD = 2.6). Clinically significant distress was reported by 63% (766/1042) of patients. Of the patient characteristics that were significantly associated with distress in the univariate analysis, a lower level of education, a higher degree of income loss, lower global quality of life, and a longer duration of radiotherapy in days remained significantly associated with higher distress in the multivariate analysis. Yet effect sizes of these associations were small. CONCLUSION: Nearly two in three cancer patients undergoing radiotherapy reported clinically significant distress in a large multicenter cohort. While screening and interventions to reduce distress should be maintained and promoted, the identified risk factors may help to raise awareness in clinical practice. TRIAL REGISTRY IDENTIFIER: DRKS: German Clinical Trial Registry identifier: DRKS00028784.

The impact of palliative radiotherapy on health-related quality of life in patients with head and neck cancer - Results of a multicenter prospective cohort study.

Purpose: Palliative radiotherapy for patients with head and neck cancer can be used to alleviate symptoms. Only a few studies have investigated its impact on patient-reported outcomes (PRO). Therefore, we conducted a prospective multicenter observational study. The primary objective was to assess changes in health-related quality of life (HrQoL) per PRO. Methods: Eligibility criteria included i.) head and neck cancer and ii.) palliative radiotherapy indicated (EQD2Gy < 60 Gy). The primary follow-up date was eight weeks after radiotherapy (t8w). PRO measures included the EORTC QLQ-C30 and EORTC QLQ-H&N43 and pain per Numeric Rating Scale (NRS). Per protocol, five PRO domains were to be reported in detail as well as PRO domains corresponding to a primary and secondary symptom as determined by the individual patient. We defined a minimal important difference (MID) of 10 points. Results: From 06/2020 to 06/2022, 61 patients were screened and 21 patients were included. Due to death or decline in health-status, HrQoL data was available for 18 patients at the first fraction and for eight patients at t8w. The MID was not met for the predefined domains in terms of mean values as compared from first fraction to t8w. Individually in those patients with available HrQoL data at t8w, 71% (5/7) improved in their primary and 40% (2/5) in their secondary symptom domain reaching the MID from first fraction to t8w, respectively. There was a significant improvement in pain per NRS in those patients with available data at t8w per Wilcoxon signed rank test (p = 0.041). Acute mucositis of grade ≥3 per CTCAE v5.0 occurred in 44% (8/18) of the patients. The median overall survival was 11 months. Conclusion: Despite low patient numbers and risk of selection bias, our study shows some evidence of a benefit from palliative radiotherapy for head and neck cancer as measured by PRO.German Clinical Trial Registry identifier: DRKS00021197.

Factors associated with suffering from dying in patients with cancer: a cross-sectional analytical study among bereaved caregivers.

BACKGROUND: In Colombia, cancer incidence is increasing, as is the demand for end-of-life care. Understanding how patients who die from cancer experience this phase will allow the identification of factors associated with greater suffering and actions to improve end-of-life care. We aimed to explore associations between the level of suffering of patients who died from cancer and were cared for in three Colombian hospitals with patient, tumor, treatment, and care characteristics and provided information. METHODS: Data on the last week of life and level of suffering were collected through proxies: Bereaved caregivers of patients who died from cancer in three participating Colombian hospitals. Bereaved caregivers participated in a phone interview and answered a series of questions regarding the last week of the patient's life. An ordinal logistic regression model explored the relationship between the level of suffering reported by bereaved caregivers with the patient's demographic and clinical characteristics, the bereaved caregivers, and the care received. Multivariate analyses were adjusted for place of death, treatments to prolong of life, prolongation of life during the dying process, suffering due to prolongation of life, type of cancer, age, if patient had partner, rural/urban residence of patient, importance of religion for the caregiver, caregivers´ relationship with the patient, and co-living with the patient. RESULTS: A total of 174 interviews were included. Median age of the deceased patients was 64 years (IQR 52-72 years), and 93 patients were women (53.4%). Most caregivers had rated the level of suffering of their relative as "moderately to extremely" (n = 139, 80%). In multivariate analyses, factors associated with a higher level of suffering were: unclear information about the treatment and the process before death Odds Ratio (OR) 2.26 (90% CI 1.21-4.19), outpatient palliative care versus home care OR 3.05 (90% CI 1.05-8.88), procedures inconsistent with the patient's wishes OR 2.92 (90% CI 1.28-6.70), and a younger age (18-44 years) at death versus the oldest age group (75-93 years) OR 3.80 (90% CI 1.33-10.84, p = 0.04). CONCLUSION: End-of-life care for cancer patients should be aligned as much as possible with patients´ wishes, needs, and capacities. A better dialogue between doctors, family members, and patients is necessary to achieve this.

Financial toxicity in cancer patients undergoing radiotherapy in a universal health care system - A prospective multicenter study of 1075 patients.

PURPOSE: To establish and confirm prevalence as well as risk factors of financial toxicity in a large national cohort of cancer patients undergoing radiotherapy in a universal health care system. METHODS: We conducted a prospective cross-sectional study offering a patient-reported questionnaire to all eligible cancer patients treated with radiotherapy in 11 centers in Germany during 60 consecutive days. The four-point subjective financial distress question of the EORTC QLQ-C30 was used as a surrogate for financial toxicity. Confirmatory hypothesis testing evaluated the primary study outcomes: overall prevalence of financial toxicity and its association with predefined risk factors. P-values < 0.05 were considered statistically significant. RESULTS: Of 2341 eligible patients, 1075 (46%) participated. The prevalence of subjective financial distress (=any grade higher than not present) was 41% (438/1075) exceeding the hypothesized range of 26.04-36.31%. Subjective financial distress was felt "A little" by 26% (280/1075), "Quite a bit" by 11% (113/1075) and "Very much" by 4% (45/1075) of the patients. Lower household income, lower global health status/ quality of life, higher direct costs and higher loss of income significantly predicted higher subjective financial distress per ordinal regression and confirmed these risk factors. Higher psychosocial distress and lower patient satisfaction were significantly associated with higher subjective financial distress in an exploratory ordinal regression model. CONCLUSION: The overall prevalence of financial toxicity was higher than anticipated, although reported at low or moderate degrees by most affected patients. As we confirmed risk factors associated with financial toxicity, patients at risk should be addressed early for potential support.

Serious Long-Term Effects of Head and Neck Cancer from the Survivors' Point of View.

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (n = 476; 46%), 'difficulty swallowing/eating' (DSE) (n = 408; 40%), 'hoarseness/difficulty speaking' (HDS) (n = 169; 16%), and 'pain in the head and neck' (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.

Adults With Congenital Heart Disease­a New, Expanding Group of Patients.

BACKGROUND: Congenital heart anomalies are the most common type of organ malformation, affecting approximately 1% of all newborn infants. More than 90% of these children now survive into adulthood. They need to be cared for by specialists for adults with congenital heart disease (ACHD), as well as by family physicians, internists, and cardiologists who are adequately versed in the basic management of persons with this lifelong condition. METHODS: This review is based on pertinent publications retrieved by a selective literature search, including guidelines and consensus statements from Germany and abroad. RESULTS: Cardiovascular malformations cover a very wide spectrum, and the evidence base for the treatment of older patients with these conditions is scant. Congestive heart failure, arrhythmias, and the sequelae of pulmonary arterial hypertension are the main contributors to cardiac morbidity and mortality. Preg - nancy counseling, endocarditis prophylaxis, vaccinations, and psychosocial aspects must be targeted to each individual patient. Neither the affected patients nor their family physicians are yet adequately acquainted with the recently created care structures for this patient group. CONCLUSION: The care of ACHD is a multidisciplinary task that requires basic care by primary care physicians as well as the involvement of specialized cardiologists in order to ensure optimal individualized treatment.

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy.

Importance: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. Objective: To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. Design, Setting, and Participants: The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. Interventions: All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Results: Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). Conclusions and Relevance: In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Dose-escalated re-irradiation improves outcome in locally recurrent head and neck cancer - Results of a large multicenter analysis.

To determine efficacy and prognostic parameters of definitive re-irradiation of locoregionally recurrent squamous cell carcinoma of the head and neck (HNSCC). MATERIALS AND METHODS: Patients with locoregionally recurrent or second primary HNSCC undergoing re-irradiation with modern radiotherapy technique were eligible for this multicentric retrospective analysis. Main endpoints were overall survival (OS), progression-free survival (PFS) and locoregional control (LC). Univariate analyses were performed using the Kaplan Meier Method (log-rank). For multivariable analysis, Cox regression was used. RESULTS: A total of 253 patients treated between 2009 and 2020 at 16 university hospitals in Germany were included. The median follow up was 27.4 months (range 0.5-130). The median OS and PFS were 13.2 (CI: 10.7 - 15.7) months and 7.9 (CI: 6.7 - 9.1) months, respectively, corresponding to two-year OS and PFS rates of 29 % and 19 %. Rates of locoregional progression and "in-field-failure" were 62 % and 51 % after two years. Multivariable Cox regression analysis identified good ECOG performance status and high radiation dose as independent prognostic parameters for OS. Doses above 50 Gy (EQD2) achieved longer median OS of 17.8 months (vs 11.7 months, p < 0.01) and longer PFS of 9.6 months (vs 6.8 months, p < 0.01). In addition, there was a trend for worse survival in patients with tracheostomy (multivariable, p = 0.061). Concomitant systemic therapy did not significantly impact PFS or OS. CONCLUSION: Re-irradiation of locally recurrent or second primary HNSCC is efficient, especially if doses above 50 Gy (EQD2) are delivered. ECOG performance score was the strongest prognostic parameter for OS and PFS.

Elucidation of the genetic causes of bicuspid aortic valve disease.

AIMS: The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. METHODS AND RESULTS: We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. CONCLUSION: Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

γ-Valerolactone as Sustainable and Low-Toxic Solvent for Electrical Double Layer Capacitors.

In this work, γ-valerolactone (GVL), a green solvent based on largely available biomass (carbohydrates), highly biodegradable, and with low eco-toxicological profile, was used as electrolyte component in energy storage devices. This solvent allowed the realization of electrolytes with good transport properties and high thermal stability, which could be successfully applied in electrical double layer capacitors (EDLCs). GVL-based EDLCs could operate at 2.7-2.9 V and displayed good performance in term of capacitance, cycling stability, as well as specific energy and power. The results of this study indicate that the use of solvent obtained from largely available natural sources is a feasible strategy for the realization of sustainable and safe electrolytes for EDLCs.