The MedXFit-study - CrossFit as a workplace health intervention: a one-year, prospective, controlled, longitudinal, intervention study.

Introduction: Workplace health interventions aim to motivate employees toward healthy behaviors to improve fitness and health in the long-term. We investigated whether CrossFit® is an effective training concept to achieve these goals in inactive employees with sedentary occupations. Methods: The study followed a prospective, controlled intervention design. Employees were invited to participate in intervention group (IG) or control group (CG) on their own preferences. Inclusion criteria were a predominantly sedentary occupation and execution of less than two muscle and/or mobility enhancing training sessions per week at the time of enrolling. The IG did at least two times a week a CrossFit training of 1 h. Mobility, strength, well-being, and back-issues were measured at the beginning, after 6, and 12 months. Participants in the CG were free to choose any other activities offered at the same time (e.g., circuit training, meditation, full body stability training). Adherence, respectively, behavioral change and maintenance qualities were evaluated based on the COM-B system and presence of behavior maintenance motives. Results: 89 employees were enrolled into the trial, from where 21 dropped out due to external factors (24%). From the remaining participants, 10 out of 39 (26%) in the IG and 1 out of 29 (4%) in the CG stopped for intrinsic reasons, leading to a non-adherence to the intervention of 22 percentage points. Motivation for behavioral change and maintenance in the IG was primarily driven by enhanced physical and psychological capability. Development of physical capability was evident by significant improvements (p < 0.001) in the IG compared to the CG for mobility (d = 3.3), maximal isometric strength (min. d = 1.7, max. d = 2.5), as well as reduction in pain intensity (p = 0.003, r = 0.4) and frequency (p = 0.009, r = 0.35) after 12 months. Significant improvements between the 6-month and the 12-month measurement in mobility and 6 out of 8 strength measures within the IG indicated the effectiveness of CrossFit beyond the beginner phase. Conclusion: CrossFit is a motivating training concept that led to long-term health and fitness improvements in inactive employees doing sedentary work and should be given greater consideration in workplace health promotion.

Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study.

Introduction: Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment of patients with HER2+/HR+ eBC is neratinib, available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria, and Switzerland. Results from an interim analysis of the first 200 patients observed for ≥3 months are reported. Methods: The primary objective of this prospective, multicenter, observational study is to assess patient adherence to neratinib (defined as the percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes. Results: At cut-off (May 2, 2022), a total of 202 patients had been observed for ≥3 months, with neratinib treatment documented for 187 patients (median age: 53.0 years; 67.9% at increased risk of disease recurrence). In total, 151 (80.7%) patients had received prior neoadjuvant treatment; of these, 82 (54.3%) patients achieved a pathologically complete response. Neratinib was initiated at a median 3.6 months after trastuzumab-based treatment, with 36.4% starting at a dose <240 mg/day. Treatment is ongoing for 46.0% of patients, with median treatment duration of 11.2 (interquartile range 0.9-12.0) months. Diarrhea was the most common adverse event (78.6% any grade, 20.3% grade ≥3); pharmacologic prophylaxis was used in 85.6% of patients. Conclusions: The pattern of anti-HER2 pretreatment observed reflected the current treatment for HER2+/HR+ eBC in Germany, Austria, and Switzerland. These interim results suggest that neratinib as an extended adjuvant is a feasible option after various anti-HER2 pretreatments and that its tolerability can be managed and improved with proactive diarrhea management.

CrossFit Motivates a 41-Year-Old Obese Man to Change His Lifestyle and Achieve Long-Term Health Improvements: A Case Report.

The purpose of this case report was to demonstrate how CrossFit (CF) as a workplace health intervention (WHI) led to long-term lifestyle changes and health improvements in an inactive, sedentary individual. Therefore, we analysed the case of a 41-year-old obese man (BMI: 41.3 kg/m2) with elevated blood pressure and poor fitness. To evaluate the factors that facilitated his behavioural change, we collected quantitative and qualitative data (from 2015 to 2022) and analysed it based on the COM-B framework. Given the already great training opportunities at his workplace, we assumed that improvements in capability and motivation led to behavioural change and maintenance. Essential for this behavioural change was the fact that CF combined health-promoting training with intrinsically motivating aspects which are typical for classic sports such as challenge, a feeling of competence, and social interaction. In conjunction with rapid fitness improvements (capability), a positive feedback cycle between capability, motivation, and behaviour developed which enabled physical activity to become habitual. As a result, blood pressure was normalized, BMI (32.9 kg/m2) and resting heart rate decreased (-20 bpm), and mobility (FMS score: +89%), strength (+14 to 71%), and well-being (WHO-5 score: +12%) increased. In conclusion, CF should be considered an effective, efficient, and safe WHI with great potential for behavioural changes and maintenance.

Corrected QT Interval (QTc) Diagnostic App for the Oncological Routine: Development Study.

BACKGROUND: Numerous antineoplastic drugs such as chemotherapeutics have cardiotoxic side effects and can lead to long QT syndrome (LQTS). When diagnosed and treated in time, the potentially fatal outcomes of LQTS can be prevented. Therefore, regular electrocardiogram (ECG) assessments are critical to ensure patient safety. However, these assessments are associated with patient discomfort and require timely support of the attending oncologist by a cardiologist. OBJECTIVE: This study aimed to examine whether this approach can be made more efficient and comfortable by a smartphone app (QTc Tracker), supporting single-lead ECG records on site and transferring to a tele-cardiologist for an immediate diagnosis. METHODS: To evaluate the QTc Tracker, it was implemented in 54 cancer centers in Germany. In total, 266 corrected QT interval (QTc) diagnoses of 122 patients were recorded. Moreover, a questionnaire on routine ECG workflow, turnaround time, and satisfaction (1=best, 6=worst) was answered by the centers before and after the implementation of the QTc Tracker. RESULTS: Compared to the routine ECG workflow, the QTc Tracker enabled a substantial turnaround time reduction of 98% (mean 2.67, 95% CI 1.72-2.67 h) and even further time efficiency in combination with a cardiologic on-call service (mean 12.10, 95% CI 5.67-18.67 min). Additionally, nurses and patients reported higher satisfaction when using the QTc Tracker. In particular, patients' satisfaction sharply improved from 2.59 (95% CI 2.41-2.88) for the routine ECG workflow to 1.25 (95% CI 0.99-1.51) for the QTc Tracker workflow. CONCLUSIONS: These results reveal a significant improvement regarding reduced turnaround time and increased user satisfaction. Best patient care might be guaranteed as the exposure of patients with an uncontrolled risk of QTc prolongations can be avoided by using the fast and easy QTc Tracker. In particular, as regular side-effect monitoring, the QTc Tracker app promises more convenience for patients and their physicians. Finally, future studies are needed to empirically test the usability and validity of such mobile ECG assessment methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04055493; https://classic.clinicaltrials.gov/ct2/show/NCT04055493.

Diagnostic Accuracy of Single-Lead Electrocardiograms Using the Kardia Mobile App and the Apple Watch 4: Validation Study.

BACKGROUND: To date, the 12-lead electrocardiogram (ECG) is the gold standard for cardiological diagnosis in clinical settings. With the advancements in technology, a growing number of smartphone apps and gadgets for recording, visualizing, and evaluating physical performance as well as health data is available. Although this new smart technology is innovative and time- and cost-efficient, less is known about its diagnostic accuracy and reliability. OBJECTIVE: This study aimed to examine the agreement between the mobile single-lead ECG measurements of the Kardia Mobile App and the Apple Watch 4 compared to the 12-lead gold standard ECG in healthy adults under laboratory conditions. Furthermore, it assessed whether the measurement error of the devices increases with an increasing heart rate. METHODS: This study was designed as a prospective quasi-experimental 1-sample measurement, in which no randomization of the sampling was carried out. In total, ECGs at rest from 81 participants (average age 24.89, SD 8.58 years; n=58, 72% male) were recorded and statistically analyzed. Bland-Altman plots were created to graphically illustrate measurement differences. To analyze the agreement between the single-lead ECGs and the 12-lead ECG, Pearson correlation coefficient (r) and Lin concordance correlation coefficient (CCCLin) were calculated. RESULTS: The results showed a higher agreement for the Apple Watch (mean deviation QT: 6.85%; QT interval corrected for heart rate using Fridericia formula [QTcF]: 7.43%) than Kardia Mobile (mean deviation QT: 9.53%; QTcF: 9.78%) even if both tend to underestimate QT and QTcF intervals. For Kardia Mobile, the QT and QTcF intervals correlated significantly with the gold standard (rQT=0.857 and rQTcF=0.727; P<.001). CCCLin corresponded to an almost complete heuristic agreement for the QT interval (0.835), whereas the QTcF interval was in the range of strong agreement (0.682). Further, for the Apple Watch, Pearson correlations were highly significant and in the range of a large effect (rQT=0.793 and rQTcF=0.649; P<.001). CCCLin corresponded to a strong heuristic agreement for both the QT (0.779) and QTcF (0.615) intervals. A small negative correlation between the measurement error and increasing heart rate could be found of each the devices and the reference. CONCLUSIONS: Smart technology seems to be a promising and reliable approach for nonclinical health monitoring. Further research is needed to broaden the evidence regarding its validity and usability in different target groups.

Favorable impact of therapy management by an interactive eHealth system on severe adverse events in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer treated by palbociclib and endocrine therapy.

BACKGROUND: Oral cancer medications offer advantages but also pose challenges for therapy management and adherence. An eHealth-based platform such as CANKADO can help to support therapy management by probing the patient's quality of life (QoL) continuously throughout the course of treatment. MATERIAL AND METHODS: AGO-B WSG PreCycle (NCT03220178) is a multicenter, randomized phase IV intergroup trial evaluating the impact of eHealth-based Patient-Reported Outcome (ePRO) assessment on QoL in patients with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer treated with palbociclib and endocrine therapy. Patients were randomized (2:1) to CANKADO-active arm (supported by CANKADO PRO-React) or CANKADO-inform arm (drug intake documentation only) This exploratory analysis reports the impact of CANKADO PRO-React on safety. Time to first serious adverse event (SAE) was estimated taking competing risks into account. RESULTS: While distributions of adverse events (AEs) were similar by arm overall, patients in the CANKADO-active arm had a favorable hazard ratio of 0.67 (95%CI 0.46-0.97; p = 0.04) for time to first SAE and were significantly less likely overall to suffer an SAE than patients in the inform arm. At 24 months, 22.9% [17.9%-27.8%] of patients in CANKADO-active had suffered an SAE vs. 30.3% [22.6%-38.0%] in CANKADO-inform. AE-related dose reductions affected approximately 20% of patients (CANKADO-active: 18.2%, CANKADO-inform: 21.1%). CONCLUSION: Exploratory safety analysis of PreCycle demonstrates for the first time in a randomized prospective trial that interactive autonomous eHealth-based support has a substantial favorable impact on the risk of SAEs and mitigates their severity for patients with advanced HR+/HER2- breast cancer on oral tumor therapy.

PRECYCLE: multicenter, randomized phase IV intergroup trial to evaluate the impact of eHealth-based patient-reported outcome (PRO) assessment on quality of life in patients with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer treated with palbociclib and an aromatase inhibitor or palbociclib and fulvestrant.

BACKGROUND: Efficacy and quality of life (QoL) are key criteria for therapy selection in metastatic breast cancer (MBC). In hormone receptor positive (HR +) human epidermal growth factor receptor 2 negative (HER2 -) MBC, addition of targeted oral agents such as everolimus or a cycline-dependent kinase 4/6 (CDK 4/6) inhibitor (e.g., palbociclib, ribociclib, abemaciclib) to endocrine therapy substantially prolongs progression-free survival and in the case of a CDK 4/6i also overall survival. However, the prerequisite is adherence to therapy over the entire course of treatment. However, particularly with new oral drugs, adherence presents a challenge to disease management. In this context, factors influencing adherence include maintaining patients' satisfaction and early detection/management of side effects. New strategies for continuous support of oncological patients are needed. An eHealth-based platform can help to support therapy management and physician-patient interaction. METHODS: PreCycle is a multicenter, randomized, phase IV trial in HR + HER2 - MBC. All patients (n = 960) receive the CDK 4/6 inhibitor palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant) according to national guidelines. PreCycle evaluates and compares the time to deterioration (TTD) of QoL in patients supported by eHealth systems with substantially different functionality: CANKADO active vs. inform. CANKADO active is the fully functional CANKADO-based eHealth treatment support system. CANKADO inform is a CANKADO-based eHealth service with a personal login, documentation of daily drug intake, but no further functions. To evaluate QoL, the FACT-B questionnaire is completed at every visit. As little is known about relationships between behavior (e.g., adherence), genetic background, and drug efficacy, the trial includes both patient-reported outcome and biomarker screening for discovery of forecast models for adherence, symptoms, QoL, progression free survival (PFS), and overall survival (OS). DISCUSSION: The primary objective of PreCycle is to test the hypothesis of superiority for time to deterioration (TTD) in terms of DQoL = "Deterioration of quality of life" (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in patients merely receiving eHealth-based information (CANKADO inform). EudraCT Number: 2016-004191-22.

Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor-Positive/ERBB2-Positive Early Breast Cancer: The Neoadjuvant WSG-TP-II Randomized Clinical Trial.

Importance: Combination of chemotherapy with (dual) ERBB2 blockade is considered standard in hormone receptor (HR)-positive/ERBB2-positive early breast cancer (EBC). Despite some promising data on endocrine therapy (ET) combination with dual ERBB2 blockade in HR-positive/ERBB2-positive BC, to our knowledge, no prospective comparison of neoadjuvant chemotherapy vs ET plus ERBB2 blockade in particular with focus on molecular markers has yet been performed. Objective: To determine whether neoadjuvant de-escalated chemotherapy is superior to endocrine therapy, both in combination with pertuzumab and trastuzumab, in a highly heterogeneous HR-positive/ERBB2-positive EBC. Design, Setting, and Participants: This prospective, multicenter, neoadjuvant randomized clinical trial allocated 207 patients with centrally confirmed estrogen receptor-positive and/or progesterone receptor-positive (>1%) HR-positive/ERBB2-positive EBC to 12 weeks of standard ET (n = 100) vs paclitaxel (n = 107) plus trastuzumab and pertuzumab. A total of 186 patients were required to detect a statistically significant difference in pathological complete response (pCR) (assumptions: 19% absolute difference in pCR; power, ≥80%; 1-sided Fisher exact test, 2.5% significance level). Interventions: Standard ET (aromatase inhibitor or tamoxifen) or paclitaxel, 80 mg/m2, weekly plus trastuzumab and pertuzumab every 21 days. Main Outcomes and Measures: The primary end point was pCR (ypT0/is, ypN0). Secondary end points included safety, translational research, and health-related quality of life. Omission of further chemotherapy was allowed in patients with pCR. PAM50 analysis was performed on baseline tumor biopsies. Results: Of the 207 patients included (median [range] age, 53 [25-83] years), 121 (58%) had cT2 to cT4 tumors, and 58 (28%) had clinically node-positive EBC. The pCR rate in the ET plus trastuzumab and pertuzumab arm was 23.7% (95% CI, 15.7%-33.4%) vs 56.4% (95% CI, 46.2%-66.3%) in the paclitaxel plus trastuzumab and pertuzumab arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P < .001). Both immunohistochemical ERBB2 score of 3 or higher and ERBB2-enriched subtype were independent predictors for pCR in both arms. Paclitaxel was superior to ET only in the first through third quartiles but not in the highest ERBB2 quartile by messenger RNA. In contrast with the paclitaxel plus trastuzumab and pertuzumab arm, no decrease in health-related quality of life after 12 weeks was observed in the ET plus trastuzumab and pertuzumab arm. Conclusions and Relevance: The WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing 2 neoadjuvant de-escalation treatments in HR-positive/ERBB2-positive EBC and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after ET plus trastuzumab and pertuzumab. Trial Registration: ClinicalTrials.gov Identifier: NCT03272477.

Evaluating the ability of an artificial-intelligence cloud-based platform designed to provide information prior to locoregional therapy for breast cancer in improving patient's satisfaction with therapy: The CINDERELLA trial.

BACKGROUND: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. METHODS: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. DISCUSSION: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome.

MedXFit-Effects of 6 months CrossFit® in sedentary and inactive employees: A prospective, controlled, longitudinal, intervention study.

Background and Aims: Sedentary behavior and physical inactivity are associated with musculoskeletal disorders (MSD). Muscle and mobility enhancing training is recommended to promote musculoskeletal fitness and prevent MSD. A functional fitness program emphasizing the importance of musculoskeletal fitness is provided by CrossFit®. However, data from long-term CrossFit® interventions assessing measures of musculoskeletal fitness in sedentary and inactive individuals does not exist. Methods: This prospective, controlled study investigates the effects of 6 months CrossFit® training (2×60 min/week) in inactive adults (in terms of <2 muscle or mobility enhancing training sessions per week) with predominantly sitting or standing occupations. 91 participants were initially assessed, 2 were excluded, 55 self-selected for intervention (IG), and 34 for the control group (CG). Primary endpoint was a change in mobility (Functional Movement Screen score). Secondary endpoints were changed in strength (maximum isometric strength in kg; Dr. Wolff BackCheck®), and well-being (WHO-5 score). Key exploratory endpoints were changes in back-issue measures (pain intensity, limitation, and frequency). Results: 39 participants of IG and 31 of CG completed the evaluation after 6 months. The IG improved significantly more (p < 0.001) compared with the CG in the FMS (η² = 0.58), trunk extension (η² = 0.46), trunk flexion (η² = 0.47), trunk lateral flexion left (η² = 0.41), trunk lateral flexion right (η² = 0.42), upper body push (η² = 0.4), upper body pull (η² = 0.25), hip extension left (η² = 0.18), and hip extension right (η² = 0.4). Change of WHO-5 scores did not significantly differ between groups (p = 0.55; η² = 0.01). Exploratory analysis of back-issue data showed a higher decrease for pain intensity, limitation, and frequency in the IG compared with the CG. Conclusion: This study proves for the first time within the scope of a prospective, controlled study the broad benefits of CrossFit® in inactive adults doing predominantly sedentary work.

Should routine risk reduction procedures for the prevention and control of pandemics become a standard in all oncological outpatient clinics? The prospective COVID-19 cohort study: protect-CoV.

Limited knowledge exists on the effectiveness of preventive preparedness plans for the care of outpatient cancer patients during epidemics or pandemics. To ensure adequate, timely and continuous clinical care for this highly vulnerable population, we propose the establishment of preventive standard safety protocols providing effective early phase identification of outbreaks at outpatient cancer facilities and communicating adapted standards of care. The prospective cohort study Protect-CoV conducted at the LMU Klinikum from mid-March to June 2020 investigated the effectiveness of a rapid, proactive and methodical response to protect patients and interrupt SARS-CoV-2 transmission chains during the first pandemic wave. The implemented measures reduced the risk of infection of individual cancer patients and ensured safe adjunctive infusion therapy in an outpatient setting during the early COVID-19 pandemic. In addition to the immediate implementation of standard hygiene procedures, our results underscore the importance of routine PCR testing for the identification of asymptomatic or pre-symptomatic COVID-19 cases and immediate tracing of positive cases and their contacts. While more prospective controlled studies are needed to confirm these results, our study illustrates the importance of including preventative testing and tracing measures in the standard risk reduction procedures at all out patient cancer centers.

A Web- and App-Based Connected Care Solution for COVID-19 In- and Outpatient Care: Qualitative Study and Application Development.

BACKGROUND: From the perspective of health care professionals, coronavirus disease (COVID-19) brings many challenges as well as opportunities for digital health care. One challenge is that health care professionals are at high risk of infection themselves. Therefore, in-person visits need to be reduced to an absolute minimum. Connected care solutions, including telehealth, remote patient monitoring, and secure communications between clinicians and their patients, may rapidly become the first choice in such public health emergencies. OBJECTIVE: The aim of the COVID-19 Caregiver Cockpit (C19CC) was to implement a free-of-charge, web- and app-based tool for patient assessment to assist health care professionals working in the COVID-19 environment. METHODS: Physicians in Argentina, Germany, Iran, Italy, Portugal, Switzerland, and the United States explained their challenges with COVID-19 patient care through unstructured interviews. Based on the collected feedback, the first version of the C19CC was built. In the second round of interviews, the application was presented to physicians, and more feedback was obtained. RESULTS: Physicians identified a number of different scenarios where telemedicine or connected care solutions could rapidly improve patient care. These scenarios included outpatient care, discharge management, remote tracking of patients with chronic diseases, as well as incorporating infected physicians under quarantine into telehealth services. CONCLUSIONS: The C19CC is the result of an agile and iterative development process that complements the work of physicians. It aims to improve the care and safety of people who are infected by COVID-19.

EVA-Scalp: Evaluation of Patient Satisfaction with a Scalp Cooling Device to Prevent Chemotherapy-Induced Alopecia in Breast Cancer Patients.

PURPOSE: Scalp cooling (SC) offers a chance to reduce hair loss (HL), but patient satisfaction, the effect on well-being, as well as patient selection criteria have not been sufficiently assessed yet. METHODS: In the EVAScalp trial, SC was offered to 70 breast cancer patients who received chemotherapy between November 2015 and September 2018. For SC, the Paxman-Orbis-II System was used. Satisfaction was measured by a questionnaire evaluating the level of depression with the WHO-5 well-being index (WHO-5) plus questions addressing the patient's experiences and side effects using the SC device. To evaluate efficacy, documentation by photo, by a physician, and by an HL-diary was conducted. RESULTS: Regarding efficacy, a significant difference between chemotherapy regimens is seen. Anthracycline-based therapies led to a stop of SC in 71% of the patients, whereas taxane-based therapies without anthracyclines were associated with a high acceptance of SC, and 88% of patients with paclitaxel-based therapies continued SC throughout their chemotherapy. Overall, only 7.69% of the patients stopped because of side effects. As an indicator for quality of life, WHO-5 was higher (65.8%) in patients with successful SC compared to in patients who stopped SC because of HL or side effects (only 53.0%). The majority of patients (82.22%) with successful SC would recommend SC to other patients. CONCLUSIONS: Patients tolerated SC as long as HL was successfully prevented. The well-being of patients with successful SC was significantly higher than that of patients who stopped SC prematurely. In general, SC is a promising approach and improves patient well-being, but there are still limitations to its utility depending on the chemotherapy regimen used.

Individualized eHealth Support for Oncological Therapy Management.

eHealth support for oncological therapy management has different faces. In addition to the direct support of therapy-supportive measures such as the promotion of physical activities, monitoring of the diet and observation of the quality of life through eHealth approaches are possible. Many solutions are now in transition between research and routine use. The most substantial evidence today is in the area of symptom monitoring. Independent studies have shown a significant survival benefit among other advantages as well. There is also a good overlap in eHealth and physical activity. More and more solutions are coming onto the market, which also has an impact for cancer patients. In the field of nutrition, there are only a few successful approaches both within and outside oncology. In contrast, the application of eHealth for the detection of disease-related malnutrition seems promising. Innovative approaches involving "artificial intelligence" or "Internet of Things" are slowly finding their place in both research and routine. For routine care, it will be necessary for doctors, nurses, and patients to know what a real medical eHealth application is and which are just lifestyle products without the needed quality for professional medical usage.

In vitro secreting profile of human mesenchymal stem cells.

In addition to their multilineage potential, mesenchymal stem cells (MSCs) also have a wide range of functionality. Not only can MSCs reconstruct a tissue, but they also have the ability to control or cure other cells and can reconstruct a coordinating function. The opportunity to control other cells depends on MSCs being able to secrete factors like cytokines and chemokines. Therefore, we focused on asking, Which factors can be secreted by human MSCs? To answer this question, we analyzed the secreting profile of in vitro-expanded MSCs by using cytokine arrays. The media concentrations of 44 of the 120 analyzed cytokines were significantly increased by MSCs. Conversely, concentrations of 40 cytokines given with the sera were significantly decreased. The data presented here provide an overview about a large range of factors that were secreted by MSCs under cell culture conditions. These data indicate that MSCs demonstrate all previously described functions in cellular interactions without an external stimulus. The MSCs secreted angiogenic, immunosuppressive, anti-apoptotic, and proliferation-stimulating factors.

Practical guidelines for diagnostic use of in vitro chemosensitivity tests.

To date, a multitude of chemotherapy sensitivity and resistance assays (CSRAs) have been developed to examine the efficiency of diverse cytostatic drugs on a patient's tumour material in vitro, and therefore provide the opportunity of customizing the particular treatment strategy in vivo. In an attempt to assess the impact of the hitherto developed CSRAs on routine clinical practice, in 2004, the American Society of Clinical Oncology (ASCO) performed a comparative analysis of previously published studies (1966 until January 2004) referring to the diverse assays and came to the conclusion that none of these assays was suitable for routine clinical practice. As the CSRAs aim to support the clinician in selecting the most efficient regimen to be applied to the individual patient, they must comply with several technical requirements. In this report, we examined the indispensable criteria for a CSRA to be broadly applicable to clinical routine use and to be meaningful for treatment recommendations not only at present but also with respect to newer cytostatic drugs in the future.

Human bone marrow stroma cells display certain neural characteristics and integrate in the subventricular compartment after injection into the liquor system.

Because the neural differentiation capacity of bone marrow stromal cells (BMSCs) is still a matter of controversial debate, we performed a thorough investigation into the differentiation capacity of human BMSCs and examined their therapeutic potency. BMSCs were isolated from the femur and kept in cell cultures with various cultivation protocols being applied. In standard culture conditions using a fetal calf serum-enriched medium, while not exhibiting a neural phenotype, the majority of cells expressed a variety of neuronal marker proteins as well as the astrocyte marker GFAP. Only a minority of stem cells expressed nestin, a marker for neural precursor cells. Cultivation in serum-free medium supplemented with specific growth factors resulted in a markedly higher percentage of nestin-positive cells. To establish the therapeutic potency of bone marrow-derived cells, the synthesis of neurotrophic factors such as NGF, BDNF and GDNF was analyzed under non-stimulating standard culture conditions as well as after a neural selection procedure. The therapeutic potency of BMSCs was further examined with regard to their migratory potential in vitro and after transplantation in vivo. After stereotactic engraftment into the lateral ventricle of adult rats, mesenchymal stem cells were seen to adhere to the ependymocytes and cells of the choroids plexus. Afterwards grafted cells passed through the ependymal barrier, locating in the subventricular space. Their BMSCs took up a close host graft interaction without any degenerative influence on the host cells. Furthermore, there was morphological as well as immunohistochemical evidence for a transdifferentiation within the host tissue. In addition, BMSCs could be efficiently transduced using a third-generation adenoviral vector, indicating their potential feasibility for a gene-therapeutic option.

Mesenchymal stem cells transmigrate over the endothelial barrier.

Mesenchymal stem cells (MSCs) seem to be a useful tool for cellular therapy in injured tissues, e.g. myocardial infarction or cardiomyopathies resulting in heart failure. For therapeutic approaches it is crucial that MSCs cross the endothelial barrier especially in intravascular or rather intracoronary application. Until today little is known about MSCs transmigrating across the endothelium. We performed co-culture experiments of MSCs on an endothelial monolayer to analyse direct interactions. An increasing flattened morphology of the MSCs was followed by a total integration into the monolayer after 2h. We repeated these experiments in isolated heart perfusions with gold-labelled MSCs. Using electron microscopy we detected MSCs exhibited direct cell-cell contacts. Tight junctions between the endothelial cells became abolished resulting in a distinct split between the cells. MSCs developed tight cell-cell contacts and became integrated into the endothelial wall of the capillary vessel. Finally, using confocal laser scanning microscopy, we assessed the ability of the MSCs to fully pass the endothelial barrier. Within the first 30 min, 30+/-8% of MSCs transmigrated, increasing to about half at 60 min (50+/-8%), whereas after 120 min the rate remained nearly unchanged (53+/-10%). This work demonstrates the capability of MSCs for transendothelial migration. Moreover we showed that the vast majority of MSCs migrated within 30 min, an important finding for the exposure times in clinical settings.

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.