Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

Psychological and work-related outcomes after inpatient multidisciplinary rehabilitation of chronic low back pain: a prospective randomized controlled trial.

BACKGROUND: This study investigated the long-term effects (12 months post-rehabilitation) of a standard inpatient multidisciplinary rehabilitation program for patients with chronic low back pain (CLBP), in which a control group (CG) received pain competence training and an intervention group (IG) received combined pain competence and depression prevention training. METHODS: In this prospective control group study with cluster-block randomization, a total of n = 583 patients were included into per protocol analyses. To examine the effects of rehabilitation on depressive symptoms, pain self-efficacy, and work ability, patients were stratified in repeated-measures analyses of variance by treatment condition (IG vs. CG), level of depressive symptoms (low vs. high), and time of assessment (pre, post, 6, and 12 months after rehabilitation). The impact of each treatment on pain-related days of sick leave (DSL; dichotomized into ≤ vs. > 2 weeks) was determined separately by conducting non-parametric analyses. Multiple imputations (n = 1225) confirmed the results. Effects were interpreted if clinical significance was given. RESULTS: Only patients with high levels of depressive symptoms showed long-term improvements in depressive symptoms and self-efficacy. Long-term improvements in work ability index and mental work ability item were restricted to the IG. Furthermore, long-term effects on pain-related DSL were ascertained by per protocol and multiple imputation analyses only for the IG. CONCLUSIONS: Patients with high levels of depressive symptoms showed improvements in depressive symptoms and self-efficacy, supporting the psychological effectiveness of both interventions. However, the beneficial long-term effects of rehabilitation on work ability and pain-related DSL among the IG support implementation of combined pain competence and depression prevention training. TRIAL REGISTRATION: DRKS00015465 (German Clinical Trial Register DRKS); date of registration: 03.09.2018.

[Aftercare Following Inpatient Rehabilitation of Patients with Obesity: Feasibility of the KgAS-Concept]. / Ambulante Nachsorge nach stationärer Adipositasrehabilitation: Machbarkeit des KgAS-Nachsorgekonzeptes.

Even though the inpatient rehabilitation of children and adolescents with obesity shows beneficial effects in short term, the relapse rate afterwards is high. Previous attempts to implement successful aftercare programs that are open to all patients were either not successful or have been cancelled. Therefore, a new program was developed and evaluated in terms of feasibility. In a cooperation of a rehabilitation clinic with aftercare specialists, 25 families were enabled to participate. During the inpatient treatment a case management was established to accompany and transfer the patients to the ambulatory care afterwards. The process and the aftercare were evaluated by questionnaires (children/adolescents, parents, aftercare specialists) as well as one-on-one interviews and a focus group with the aftercare specialists that were also analyzed. Results show the feasibility of the program and good satisfaction rates among all participating groups (children/adolescents, parents, aftercare specialists, inpatient rehabilitation center). Thus, the program might be eligible in the treatment process. However, the evaluation of the effectiveness in a randomized controlled study is recommended.

[Patient Education Programs in Child and Adolescent Rehabilitation]. / Patientenschulung in der Kinder- und Jugendlichenrehabilitation.

Comprehensive evidence has been provided for the significant increase in most chronic physical illnesses among children and adolescents. Therefore, early diagnosis and multimodal intervention in childhood and adolescence is required to prevent a chronic course of disease. Thus, patient education is essential for the medical child and adolescent rehabilitation. In particular, in developing asthma, atopic dermatitis and obesity training in the past, a basic consensus on the theory and methodology of patient education has emerged. Specifically, in addition to illness-specific modules, generic modules and treatment objectives should be incorporated.

[Is the relationship between fear-avoidance cognitions and quality of life mediated by depressive symptoms?] / Mediiert die Depressivität die Beziehung zwischen Angst-Vermeidungs-Kognitionen und Lebensqualität?

BACKGROUND: Chronic low back pain is often accompanied by fear-avoidance cognitions, increased depressive symptoms and decreased quality of life. OBJECTIVE: Is the relationship between fear-avoidance cognitions and quality of life mediated by depressive symptoms? METHODS: Mediation analyses were conducted to predict the long-term quality of life with depressive symptoms as mediator using longitudinal data from 131 patients. RESULTS: Fear-avoidance cognitions prior to rehabilitation predicted the physical quality of life 24 months after rehabilitation, which was mediated by the degree of depressive symptoms 6 months after rehabilitation. The other assumed models could not be tested due to non-significant correlations between the model variables. CONCLUSION: To improve the physical quality of life, depressive symptoms should be included into the treatment of chronic low back pain.

Psychological Aspects in the Treatment of Chronic Low Back Pain in Germany: A Review.

Bei chronischen, nicht spezifischen Rückenschmerzen haben psychische Komorbiditäten deutlich zugenommen, sodass im Rahmen einer multimodalen Behandlung zunehmend auch psychotherapeutische Behandlungsansätze implementiert werden. Ziel dieses Reviews war es, die aktuelle Forschung zu psychologischen Aspekten bei der Behandlung von chronischen Rückenschmerzen zu thematisieren. Dazu wurde eine selektive Literaturrecherche durchgeführt, um Studien aus Deutschland zu identifizieren, die in den letzten 5 Jahren veröffentlicht wurden. Dabei wurden 12 Artikel von 5 Forschergruppen gefunden, die unterschiedliche Aspekte der stationären, teilstationären und ambulanten Rehabilitation sowie der Nachsorge thematisierten. Die Evidenz für die Effektivität von psychologischer Behandlung bei chronischen Rückenschmerzen ist in den letzten Jahren gestiegen, gerade im Bereich der Nachsorge ist jedoch weitere Forschung für eine erfolgreiche Implementierung notwendig.

[Promoting Factors, Barriers and Barrier Management to the Implementation of Health-Promoting Behavior among Rehabilitative Patients with Chronic Low Back Pain - A Qualitative Analysis]. / Förderfaktoren, Barrieren und Barrierenmanagement zur Umsetzung gesundheitsförderlicher Verhaltensweisen von Rehabilitanden mit chronischem Rückenschmerz - Eine qualitative Analyse.

UNLABELLED: Backgroundand aim: The long-term success of rehabilitation in chronic low back pain is not yet established. The present study examined promoting factors, barriers and barrier management of health-promoting behavior among rehabilitative patients. METHOD: In total, 35 documents of patients of 4 inpatient behavioral medicine orthopedic rehabilitation clinics were included into the analysis of a written survey based on 3 open questions. The free-worded statements were electronically recorded and then analyzed by content analysis. RESULTS: Promoting factors of patients for the implementation of healthy life style behaviors included the learning of techniques for pain and stress management as well as increased volition and quality of life. Among patients with increased depressive symptoms, insufficient volition, family and professional pressures were identified as barriers. Finally, social support was reported to facilitate implementing health-promoting behavior into daily life. CONCLUSIONS: The results suggest that the long-term rehabilitation success can be improved by treating exercises to implement health-promoting behavior into daily life, applying individualized barrier management, and offering post-rehabilitative treatments in all communities.

[Patients with chronic low back pain: the impact of psychosocial features]. / Patienten mit chronisch unspezifischem Rückenschmerz: Zur Bedeutung psychosozialer Merkmale.

BACKGROUND: Chronic low back pain (CLBP) is often associated with clinical and subclinical levels of psychological problems. A higher stage of chronicity is associated with an increase in co-existing psychological disorders. Previous programmes of inpatient orthopaedic rehabilitation reveal little evidence of sustained rehabilitation effects, a finding which may be attributable to the absence of specific psychological treatment during the programme. PURPOSE: Does cognitive-behavioural depression management training in patients with CLBP and depressive symptoms improve the inpatient orthopaedic rehabilitation success depending on the stage of chronicity? METHOD: Effects of the new programme on psychological well-being (ADS depressive symptoms, HADS anxiety, SCL somatization and mental health of the SF-12) were investigated in n=75 patients with first and second stage of chronicity immediately after, six months after and 24 months after rehabilitation and were compared to standard rehabilitation without management of depressive symptoms. RESULTS: All patients benefited from both treatments immediately after rehabilitation. However, six months after rehabilitation only patients of the intervention group showed significant beneficial effects with regard to depressive symptoms and mental health. The lowered depressive symptoms remained stable up to the 24-month follow-up assessment. Anxiety in the second stage of chronicity was reduced up to the 6-month follow-up and in the first stage up to the 24-month follow-up. CONCLUSIONS: The new programme with a cognitive-behavioural depression management training revealed beneficial effects on mental health in the mid-term and on depressive symptoms in the long-term. However, the effects need to be further improved by after-care programmes.

[Pain staging, gender, and rehabilitation outcome in chronic low back pain. A pilot study]. / Schmerzchronifizierung, Geschlecht und Rehabilitationserfolg bei chronischem Rückenschmerz. Eine Pilotstudie.

BACKGROUND: Current biopsychosocial models of the etiology and chronicity of back pain postulate a major impact of psychological factors in the process of back pain chronicity. PARTICIPANTS AND METHODS: Effects of gender and pain staging on rehabilitation outcome were examined immediately after and 3 and 6 months after rehabilitation in 121 patients with chronic low back pain (43 women, 78 men; M=48 years; ICD-10 diagnoses M54.4/M54.5). Pain was staged using the Mainz Pain Staging System. RESULTS: In the short and mid term, patients in stage I and women benefited from rehabilitation. Rehabilitation outcomes tended not to be improved for men in stage III. CONCLUSIONS: Results support the notion that rehabilitation outcome is significantly influenced by pain staging and gender. Thus, clinical-psychological and gender-specific interventions should be incorporated in future therapeutic regimens to increase the rehabilitation outcomes in patients with higher chronicity of back pain.

[Psychosocial factors in chronic low back pain in orthopaedic inpatient rehabilitation. An analysis using the axes of the Mainz Pain Staging System]. / Psychosoziale Faktoren der Schmerzchronifizierung bei Patienten in der stationären orthopädischen Rehabilitation von chronisch unspezifischem Rückenschmerz. Analyse anhand der Achsenstadien des MPSS.

BACKGROUND: The aim of this study was to investigate the criterion validity of the Mainz Pain Staging System (MPSS), considering the four axes of the MPSS separately. METHODS AND DESIGN: Psychological and pain-related impairments were analysed depending on the stage of axis (I, II, III) for each single axis of the MPSS in a consecutive sample of 280 patients with chronic low back pain in orthopaedic inpatient rehabilitation. In addition, the distribution of frequency of clinically significant symptoms in depression, anxiety and somatisation were examined depending on the stage of axis. RESULTS: For all axes, an increasing stage was associated with greater psychological and pain-related impairments. Particularly patients assigned to stage III on axis 1 (temporal aspects) and 2 (spatial aspects) and patients assigned to stage II on axis 3 (drug intake) and 4 (utilisation of the health care system) showed enhanced psychosocial impairments and more frequently had clinically relevant symptoms in psychological variables. CONCLUSION: Findings confirm the criterion validity of the MPSS for chronic low back pain. In addition, results support the significance of psychosocial factors for the further development of chronicity.

[Staging of pain in patients with chronic low back pain in inpatient rehabilitation: validity of the Mainz Pain Staging System of pain chronification]. / Schmerzchronifizierung bei Rückenschmerzpatienten in der stationären Rehabilitation: Zur Validität des Mainzer Stadienmodells der Schmerzchronifizierung.

BACKGROUND: Criterion-related validity of the Mainz Pain Staging System (MPSS) was examined. PATIENTS AND METHODS: The effect of staging of pain on pain-related and psychosocial measures was investigated in a cross-sectional design among 478 patients with chronic low back pain in inpatient orthopedic rehabilitation (ICD-10 diagnoses: M45.4/M45.5, M54.4/M54.5). Pain-related measures were selected from the German Pain Questionnaire of the International Association for the Study of Pain (DGSS). The psychosocial measures depression (ADS), anxiety (HADS-D), somatization (SCL-90-R), quality of life (SF-12), functional capacity (FFbH-R), pain sensation (SES) as well as pain experience and strategies of coping with pain (FESV) were assessed. Furthermore, the frequency distribution of scores in the clinical range in pain-related and psychosocial measures depending on the staging of pain was examined. Finally, initial indications of the predictive validity of the MPSS were investigated among 116 inpatients. RESULTS: Staging of pain had a significant impact both on levels of measures and proportion of clinically referred patients. Patients in stage III, but also those in stage II showed significantly impaired levels. Patients in stage III also showed more scores in the clinical range than expected in the lowest pain intensity, ADS depression, somatization of the SCL, functional capacity, and pain sensation. The MPSS before rehabilitation, together with mental health, seem to be a good predictor of depressive symptoms 6 months after rehabilitation. CONCLUSION: The results support criterion validity of the MPSS, however, they also corroborate the concept that identification of medium and high grade pain by the MPSS has to be followed by a psychological diagnostic assessment. By this stepwise diagnostic process, therapy aims and treatment regimens can be designed more adequately.

[Influence of depressive symptoms and gender in chronic low back pain rehabilitation outcome: a pilot study]. / Der Einfluss von Depressivität und Geschlecht auf den Rehabilitationserfolg bei chronischem Rückenschmerz: Eine Pilotstudie.

Currently, little is known about the influence of depressive symptoms and gender-specific aspects in rehabilitation outcome of patients with chronic low back pain. Effects of gender and depressive symptoms on rehabilitation outcome were examined immediately after rehabilitation, as well as three and six months after rehabilitation in 116 patients with chronic low back pain (43 women, 73 men; M=48 yrs.; ICD-10 diagnoses: M45.4/M45.5, M54.4/M54.5). Immediately after rehabilitation, general improvements with medium effect sizes in all rehabilitation measures were found. In contrast, six months after rehabilitation, only pain-related measures showed moderate improvements. Additionally, the mid-term outcomes were influenced by gender and depressive symptoms; women showed more stable rehabilitation outcomes in pain intensity, in the impaired function related to family/leisure, and the coping with pain strategies of "perceived self-competence" and "relaxation". In contrast, especially male patients with severe depressive symptoms revealed regressive rehabilitation outcomes, both in pain-related variables as well as marginally in the coping with pain strategy of "cognitive restructuring". In post-hoc analyses, in the mid-term, they even showed a deterioration of functional capacity and somatisation compared to prior to rehabilitation. Our results suggest that the outcome of orthopaedic rehabilitation may be persistently improved by implementing gender-specific treatments in general and elements of depression treatments for the patients with severe but sub-clinical depressive symptoms.

[Rehabilitation of children and adolescents]. / Rehabilitation von Kindern und Jugendlichen.

In recent years a significant increase in most chronic mental and physical illnesses among children and adolescents was reported. Thus, medical child and adolescent rehabilitation plays a major role. Therefore, early diagnosis and multimodal intervention in childhood and adolescence is necessary, to prevent a chronic course of disease. Patient education programs have been shown to be effective in the treatment of chronic illnesses. Those programs are mostly aimed to improve the compliant behavior and disease management. Consecutively, the health status and quality of life should be improved. Due to the implementation of guidelines and evaluation studies the quality of rehabilitation programs was ameliorated during the past 15 years. However, future research should develop flexible rehabilitation programs in particular (rehabilitation duration, rehabilitation near or far from place of residence, rehabilitation chain with in-patient, partially out-patient, and out-patient programs), whose effectiveness has to be proven.

[Multimodal therapy of children with attention deficit/hyperactivity disorder and their parents in in-patient rehabilitation]. / Multimodales Therapiekonzept für Kinder mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen und deren Begleitperson in der stationären Rehabilitation.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is one of the most frequent psychic disorders of childhood, characterized by high persistence and an increased risk for the development of externalising disorders of behavior. Due to ADHD increased problems can be frequently observed at school as well as in the social and emotional context of the child. Concepts for in-patient rehabilitation have not been developed, although effective modifications of the behavior of ADHD patients appeared to be achievable under the conditions found in in-patient rehabilitation. OBJECTIVE: The present pilot study aimed to evaluate whether this newly developed concept has any benefit on psychological problems, coping and quality of life. METHOD: In total, n = 28 boys with ADHD 7 to 12 years old were included into a quasi-experimental pre-post design and completed self-report questionnaires on psychological problems, coping and quality of life. In addition, 26 mothers evaluated the behavior problems, psychological problems and quality of life of their sons at the beginning and the end of in-patient rehabilitation. During a 4-week in-patient rehabilitation all children and their mothers took part in a multimodal training containing components of behavior therapy and cognitive-behavioral therapy (self-instruction, self-management, and stress management), applied in child-, parent-child- and parent-centered interventions. RESULTS: Parents estimated the behavior problems of their children as significantly reduced after in-patient rehabilitation as compared to before. In addition, psychological problems and quality of life improved significantly in self- and parent-proxy reports during the in-patient rehabilitation. CONCLUSION: Our results support the hypothesis that this multimodal therapy concept is an effective tool for the treatment of ADHD patients. However, a replication of our results in a control-group study on a larger population is required.

Effects of nucleotides and divalent cations on phospholipase activity in Saccharomyces cerevisiae.

Divalent cations activate the lysophospholipase and transacylase reactions catalyzed by the same enzymes in the yeast Saccharomyces cerevisiae. The activation was observed at neutral pH, but not at the pH optimum of lysophospholipase/transacylase, near 3.5. Adenine nucleotides, especially AMP and ADP, are strong inhibitors of the same group of enzymes. Half maximal inhibition by AMP was found at a concentration of about 20 microM. The inhibition by nucleotides in low concentrations is enhanced by divalent cations.