Long-term care, care needs and wellbeing of individuals after cancer in childhood or adolescence (VersKiK): study protocol of a large scale multi-methods non-interventional study.

BACKGROUND: It has been shown previously that a relevant proportion of childhood cancer survivors suffers from late effects, which are often directly related to the cancer itself or its therapy, resulting in particular follow-up needs, additionally burdening healthcare systems. Being diagnosed with cancer at a vulnerable stage of development, this group of cancer survivors is at comparatively higher risk of relapse or subsequent cancer. Although national and international follow-up guidelines based on treatment modalities have been developed, their implementation seems to leave room for improvement. Additionally, they lack a sufficient consideration of the survivors' psychosocial needs, affecting their adherence to them. The aim of the VersKiK study is to provide representative information on late effects in childhood and adolescence cancer survivors in Germany. The main research objectives are: (1) to describe the state of follow-up care among survivors after a cancer diagnosis in childhood or adolescence; (2) to quantify the occurrence of late effects among this group of survivors; (3) to examine the adherence to selected audiological and cardiological follow-up guidelines and to identify factors affecting it; (4) to explore actual follow-up needs of paediatric cancer survivors; (5) to review selected follow-up guidelines with the aim to improve and expand them. METHODS: VersKiK is designed as a mixed-methods non-interventional study. We will use claims data from statutory health insurance companies in combination with individually linked population-based registry data from the German Childhood Cancer Registry (GCCR). This data base will permit us to quantify diagnoses and procedures in comparison to the general population as well as the adherence to existing follow-up guidelines. Additional information will be obtained through interviews with childhood and adolescence cancer survivors and their informal caregivers, as well as in focus groups with healthcare professionals. DISCUSSION: The present study aims to research the actual needs of individuals after cancer diagnosis and treatment in childhood or adolescence - physical, psychological and organisational - in order to improve existing follow-up guidelines. These improvements might further positively affect not only actual care provided to paediatric cancer survivors, but also benefit healthcare systems in general while decreasing consequent medical visits in this group of patients. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00025960 and DRKS00026092).

Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

[Pathological-anatomical diagnosis according to the German lung cancer guideline 2018]. / Pathologisch-anatomische Diagnostik gemäß S3-Leitlinie Lungenkarzinom 2018.

The German S3-guideline on prevention, diagnosis, therapy and follow-up of lung cancer, published in February 2018, expands on the 2010 guideline to include a total of 19 recommendations and statements regarding the "processing of lung resection specimens (tumor resection specimens)", "processing of lymph nodes", "histo-pathological typing and immunophenotype", "extent of tumor growth in resection specimens", "resection margins" or "R-classification", "grade of malignancy (grading)", "regression grading" as well as the "examination of molecular targets". The statements regarding the analysis of molecular targets result from the diagnostic requirements of the current targeted therapy of advanced lung cancer. At the same time, a pathological-anatomical diagnosis according to the current S3-guideline fulfills all corresponding requirements in certified lung cancer centers.

[Late effects following childhood cancer treatment : A special challenge for transition medicine]. / Spätfolgen einer Krebsbehandlung im Kindes- und Jugendalter : Eine Herausforderung für die Transitionsmedizin.

BACKGROUND: Childhood cancer survivors are at risk of cancer- and treatment-related chronic health conditions. Since these sequelae may occur years after the end of treatment, many patients are already adults and have completed pediatric oncological care. Thus, successful transition is essential in order to ensure long-term surveillance. OBJECTIVES: The present review outlines the most frequent late effects of childhood cancer treatment. Moreover, difficulties in transition of these patients are discussed and interdisciplinary models of care are presented. RESULTS: Late effects following childhood cancer treatment occur in over two thirds of patients 30 years after the end of the oncological treatment and can affect different organs. The most frequent sequelae are endocrine disturbances, cardiac conditions, and subsequent neoplasms. Many late effects are effectively manageable if detected early. This necessitates an interdisciplinary approach as well as life-long surveillance. CONCLUSIONS: Transition from pediatric to internal medicine care as well as a change in the focus of care, shifting from relapse centered follow-up to late-effects centered surveillance, constitute a special challenge for a successful transition of long-term childhood cancer survivors. Specialized late-effects survivorship clinics offering interdisciplinary care from pediatric oncologists, specialists of internal medicine, and further disciplines enable the early diagnosis and treatment of late-effects.

[How are Pediatric Hospitals in North-Rhine Westfalia Prepared to Overcome Language Barriers? A Pilot Study Exploring The Structural Quality of Inpatient Care]. / Wie sind Kinder- und Jugendkliniken in Nordrhein-Westfalen auf die Überwindung von Sprachbarrieren vorbereitet? ­ Eine Pilotstudie zur Strukturqualität in der stationären Gesundheitsversorgung.

Background In Germany, 35% of all children are considered to have a "migration background", and in the state of North-Rhine-Westfalia 43%. Frequently, one or both parents of a patient with a migration background have limited German language proficiency. Communication barriers due to a language difference can have a negative impact on quality of care, patient safety and costs of care. In this study, we investigate how children's hospitals are prepared to meet the challenges associated with language barriers. Methods We surveyed all children's hospitals in the state of North-Rhine-Westfalia, Germany. The questionnaire was based on the "Standards for Culturally and Linguistically Appropriate Services in Health and Health Care (CLAS)" and was adapted to circumstances in Germany. Results Thirty-eight hospitals participated (51%) in this survey. Language barriers occurred frequently (75% of respondents mentioned language difficulties in more than 10% of the patient population). 82% of respondents rated their hospital to be "less than well prepared" to overcome language barriers. In the majority of hospitals (62%), the need for an interpreter was determined on a case-to-case basis and not according to any set protocol. In most cases bilingual staff was used for interpreting. However, only 38% of respondents found a list of available bilingual staff to be a sufficient resource. 42% of respondents did not know the monthly costs for professional interpreting services. In the remaining cases, costs were less than € 500/month. Conclusion To overcome language barriers, hospitals rely on local resources. The majority of respondents did not find them to be appropriate and sufficient. The development of quality standards and the provision of financial resources are necessary to mobilize this potential for improvement. Therefore, other disciplines and sectors of healthcare need to be analyzed in order to provide the evidence for a constructive discussion with decision makers in policy and health insurance.

High spatial resolution, low-noise Brillouin dynamic gratings reflectometry based on digital pulse compression.

Digital pulse compression was used to enhance the performance of optical time-domain reflectometry, employing Brillouin dynamic gratings (BDGs) in polarization-maintaining fibers. The fundamental and unique issues in BDG field-reflection are addressed, and rules for proper selection of the coding and detection techniques are formulated. While coding in BDG applications generally requires coherent processing of the reflection, conditions are established for use of direct detection. A 256-bit Golay complementary unipolar probe code is used to demonstrate an eightfold signal-to-noise ratio enhancement in the measurement of the Brillouin gain spectrum (BGS), with a spatial resolution of 2 cm and a full-BGS acquisition rate of 133⅓ kHz, resulting in an equivalent reduction in the estimation error of small Brillouin frequency shifts.

Design, implementation, and evaluation of a mobile application for patient empowerment and management of long-term follow-up after childhood cancer.

In Germany, about 1,800 new cases of childhood cancer are diagnosed every year. The chances of survival have increased significantly over the last 40 years due to the continuous improvement of treatment strategies. The number of childhood cancer survivors in Germany thus ranges around 30,000 nowadays. But their treatment with surgery, chemotherapy, and radiation has certain side-effects. In addition to the acute effects during the treatment phase, the disease- and treatment-related late effects can occur even decades after the end of therapy. These late effects draw attention as the survival rate constantly increases. Two-thirds of the former patients retain long-term consequences, nearly a fifth with a resulting diminished quality of life. Early detection of these late effects can help to reduce or even to prevent serious health damage. Therefore, the study group LESS supplies long-term follow-up recommendations for former patients. The project described in this paper was to design and implement a mobile application to increase the compliance for this aftercare program. This application provides information about the patient's individual aftercare plan and supports appointment management as well as a reminding functionality. A prototype for former osteosarcoma patients was tested and evaluated in two university hospitals. First results show the application's very high potential for patient empowerment.

Anisotropic dispersion and partial localization of acoustic surface plasmons on an atomically stepped surface: Au(788).

Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized. Our investigation identifies, for the first time, ASPs coupled with intersubband transitions involving multiple surface-state subbands.

Positive or negative fructose breath test results do not predict response to fructose restricted diet in children with recurrent abdominal pain: results from a prospective randomized trial.

OBJECTIVES: To perform a prospective, blinded, randomized interventional trial in patients with recurrent abdominal pain. The primary endpoint was to determine the abdominal pain intensity after 2 weeks of fructose restricted diet. Secondary endpoints were changes of pain frequency and a secondary symptom score (SSS). METHODS: 103 individuals with recurrent abdominal pain for more than 3 months were randomized. 51 patients were allocated to group A (diet) and 52 to group B (no diet). 2 weeks later the patients underwent hydrogen breath test and were assigned to the test positive or negative group to identify patients with fructose malabsorption. RESULTS: 2 weeks after intervention the pain score decreased significantly from a median 5.5 in group A to 4 and did not change significantly in group B (5.3 to 5). In group A both patients with positive and negative breath tests had a significant lower pain score (-2 and -1.75, respectively). Frequency of abdominal pain decreased in both groups but without significant difference, SSS improved only in group A from median 6 to 3.5. Positive breath test was no predicting factor, neither was abdominal pain during the test. CONCLUSIONS: Fructose restricted diet in children and adolescents with recurrent abdominal pain may be of benefit to improve both abdominal pain symptoms and other secondary symptoms. Since a negative breath test result does not exclude a positive response to fructose restriction, the hydrogen breath test does not seem to be the appropriate diagnostic mean to predict the response to the diet.

A methodological protocol for the development of a national guideline on perioperative management of gastrointestinal tumors in Germany.

BACKGROUND: The success of abdominal cancer surgery depends not only on the surgery itself but is influenced by the overall perioperative management. Given the multitude of perioperative measures and the ever-increasing number of studies on perioperative management, it is difficult to keep track and provide evidence-based perioperative management. The planned guideline on perioperative management will review the existing evidence and derive treatment recommendations. METHODS: The processing of the evidence is carried out by 6 working groups according to an 8-step scheme: after drafting the guideline questions in PICO format (1), a systematic literature search is carried out (2), and the records found are screened by two independent reviewers from the coordination team. Subsequently, the full texts of the potentially relevant articles are made available to the working groups for full text screening (3). All articles to be included are reviewed for methodological quality (4) before summary of findings tables are generated (5). In line with the GRADE approach, confidence in the evidence is assessed (6) before a recommendation is derived from the evidence, using a modified GRADE Evidence to Decision Framework (7). Finally, all recommendations are compiled and agreed within the guideline group (8). DISCUSSION: Guidelines serve as foundation for therapy decisions in everyday clinical practice and should therefore be based on up-to-date research results. However, while primary studies and systematic reviews are critically reviewed for their methodological quality, the process of guideline development is often not comprehensible. A protocol with predefined methodology should therefore create transparency and strengthen confidence in the recommendations. TRIAL REGISTRATION: The guideline is registered in the AWMF (Association of the Scientific Medical Societies) Guideline Register (088-010OL).

Enhanced spontaneous backscattering in Brillouin dynamic gratings.

Spontaneous Brillouin backscattering, which accompanies the operation of Brillouin dynamic gratings (BDGs) setups, is investigated both theoretically and experimentally. It is shown that this noisy emission, which cannot be separated from the signal of interest, contains not only the probe spontaneous Brillouin backscattering but also a significant contribution from the spontaneous/stimulated acoustic field, originating from the high-frequency writing pump. In the absence of the low-frequency writing pump and for a strong enough high-frequency writing pump, the observed Stokes noise can exhibit an average backscattered power much higher than that from the probe alone.

Correlated motion of electrons on the Au(111) surface: anomalous acoustic surface-plasmon dispersion and single-particle excitations.

The linear dispersion of the low-dimensional acoustic surface plasmon (ASP) opens perspectives in energy conversion, transport, and confinement far below optical frequencies. Although the ASP exists in a wide class of materials, ranging from metal surfaces and ultrathin films to graphene and topological insulators, its properties are still largely unexplored. Taking Au(111) as a model system, our combined experimental and theoretical study revealed an intriguing interplay between collective and single particle excitations, causing the ASP associated with the Shockley surface state to be embedded within the intraband transitions without losing its sharp character and linear dispersion.

[Language barriers in the care for pediatric immigrant patients -- results of a pilotstudy among pediatricians in Germany]. / Sprachbarrieren in der Betreuung von Patienten mitMigrationshintergrund ­ Ergebnisse einer Pilotstudiezu den Erfahrungen von Kinder- und Jugendärzten

BACKGROUND: In 2010, 19.3% of German inhabitants were either first or second generation immigrants. Language barriers can potentially impair quality of care of this heterogenous group of patients. It has not yet been studied how pediatricians practicing in Germany experience and cope with language barriers. METHODS: We conducted a written survey among participants of the 105th annual meeting of the German Society of Pediatrics in 2009. The questionnaire was newly developed and consisted of 39 items and 3 open questions. Frequency distribution and cross tables were used for descriptive analysis of categorical data. RESULTS: 229 participants returned the questionnaire (40% in inpatient care, 33% in private practice, 26% in public outpatient services). 75% of participants are confronted with language barriers regularly. The most widespread strategy to overcome barriers is using bilingual colleagues, employees or patient family members as interpreters. The opportunity to access professional interpreters depends on the care setting (22% [inpatient care] vs. 5% [private practice] vs. 28% [public outpatient service]). 91% claim that the expenditure of time to organize professional interpreting services is high. CONCLUSION: The results of the pilot project suggest that the possibilities to overcome language barriers largely depend on the care setting. A high amount of organizational work and vague financing currently limit the use of professional interpreting services. However, health politics and science increasingly demand their use.

YouTube as a source of information for children with paroxysmal episodes.

Whereas to date the internet is a main source of information for many parents, there are no restrictions regarding data presentation. Thus, the aim of this study was to assess the quality of internet material concerning paroxysmal episodes.We rated videos on YouTube for several conditions like infantile spasms, absence seizures, Sandifer syndrome, sleep myoclonus, and shuddering attacks. Videos were classified into different categories of certainty of diagnosis according to expert opinion based on a 4 point Likert scale followed by calculation of interrater reliability. Also the quality of supplemental information was assessed, as well as whether videos were helpful from a neuropaediatrican's point of view in counselling patients and their parents.In sleep myoclonus, absences and infantile spasms correlation between title of videos and classification by expert opinion was good. There was more discrepancy with the videos concerning Sandifer syndrome and shuddering attacks. Interrater reliability was low for Sandifer syndrome, fair for absences, shuddering attacks and sleep myoclonus and moderate for infantile spasms. Some supplemental information was rated to be helpful but other information was found to be misleading or even unsettling for patients and their parents.We consider that video material on YouTube can generally not be considered as helpful for parents because of a significant disagreement between experts, even for the most well defined disorders in our study.

Helmet continuous positive airway pressure for patients' transport using a single oxygen cylinder: A bench study.

BACKGROUND: Continuous positive airway pressure (CPAP) is frequently used to treat patients with acute respiratory failure in out-of-hospital settings. Compared to a facemask, the helmet has many advantages for the patient but requires a minimum gas flow of 60 L/min to avoid CO2 rebreathing. The aim of the present bench study was to evaluate the performance of four Venturi devices, connected to a single oxygen cylinder, in delivering helmet-CPAP with clinically relevant gas flow, fraction of inspired oxygen (FiO2), and positive end-expiratory pressure (PEEP) values. METHODS: Three double-inlet Venturi systems (EasyVent, Ventuplus, Compact-HAR) were connected to full 5-L oxygen cylinders using a double flowmeter, and their oxygen requirements to reach different setups (flow 60-80 L/min; FiO2 0.4-0.5-0.6, PEEP 7.5-10-12.5 cmH2O) were tested. The fourth Venturi system (O2-MAX) was directly attached to the tank, and the flow and FiO2 delivered at preset FiO2 0.3 and 0.6 were recorded. The runtime of the cylinder was assessed. RESULTS: EasyVent, Ventuplus, and O2-MAX were able to deliver helmet-CPAP with clinically useful setups when connected to a single oxygen cylinder, while Compact-HAR did not. The runtime of the cylinders ranged between 28 and 60 minutes according to the preset flow and FiO2. The delivered gas flow decreased slowly and linearly with the drop in cylinder pressure until its exhaustion. CONCLUSIONS: Helmet-CPAP might be provided using portable Venturi systems connected to an oxygen cylinder, but not all of them are able to deliver it. The use of a double flowmeter allows delivery of both high flow and high FiO2 when double-inlet Venturi systems are used. Due to the flow drop observed during the cylinder consumption, a flow >60 L/min should be set when helmet-CPAP is started. Considering the flow drop phenomenon, the estimated duration of the tank runtime can be used with a margin of safety when planning patient transport.

VersKiK: Study protocol of an observational registry-based study on the current state of follow-up care and adherence to follow-up guidelines after cancer in childhood or adolescence.

BACKGROUND: This article describes the study design of the quantitative part of the VersKiK study, The primary objectives of this study are to examine the occurrence of late effects in survivors of childhood or adolescent cancer (module 1), investigate health-related vulnerabilities and medical service utilization within this survivor group (modules 1 and 3), and assess the alignment between documented follow-up care for cardiological and audiological late effects with guideline recommendations, along with evaluating the extent of adherence among paediatric cancer survivors (module 3). METHODS: This is a non-interventional retrospective observational cohort study. It is based on stochastically linked insurance claims data from approximately 150,000 statutory insured persons with information concerning around 25,000-30,000 cancer survivors recorded in the German Childhood Cancer Register (GCCR). To explore adherence to selected follow-up guidelines, intention to treat treatment data from clinical study groups for particular diagnostic entities will be additionally included. DISCUSSION: The growing group of survivors after cancer in childhood and adolescence is representing a special population with an increasing demand for life-long healthcare services through relative high probability of late effects. Currently, there is a limited evidence in Germany on utilization of corresponding medical services and adherence to follow-up guidelines. With this study design, we are aiming to address these gaps and, consequently, suggest improvements to existing follow-up guidelines and follow-up care provision in Germany.

Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients.

BACKGROUND: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a promising immunotherapeutic approach for patients with advanced solid tumors. While numerous advances have been made, the contribution of neoantigen-specific CD4+T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. METHODS: We analyzed infused TIL products from metastatic melanoma patients previously treated with ACT for the presence of neoantigen-specific T cells. TILs were enriched on reactivity to neoantigen peptides derived and prioritized from patient sample-directed mutanome analysis. Enriched TILs were further investigated to establish the clonal neoantigen response with respect to function, transcriptomics, and persistence following ACT. RESULTS: We discovered that neoantigen-specific TIL clones were predominantly CD4+ T cells and were present in both therapeutic responders and non-responders. CD4+ TIL demonstrated an effector T cell response with cytotoxicity toward autologous tumor in a major histocompatibility complex class II-dependent manner. These results were validated by paired TCR and single cell RNA sequencing, which elucidated transcriptomic profiles distinct to neoantigen-specific CD4+ TIL. CONCLUSIONS: Despite methods which often focus on CD8+T cells, our study supports the importance of prospective identification of neoantigen-specific CD4+ T cells within TIL products as they are a potent source of tumor-specific effectors. We further advocate for the inclusion of neoantigen-specific CD4+ TIL in future ACT protocols as a strategy to improve antitumor immunity.