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Myasthenia gravis (MG) is an antibody-mediated immune disorder of the neuromuscular junction. SARS-CoV-2 is now recognised as a trigger factor for autoimmune diseases and to cause immune-mediated dysregulation, likely due to molecular mimicry induced by viral antigens. SARS-CoV-2 vaccination, similarly, results in exposure to viral antigen. Here we report 7 cases of new-onset myasthenia gravis in timely association with SARS-CoV-2 vaccination, including the first paediatric case identified to date. We also reviewed the literature for other new-onset MG cases reported within 4 weeks of SARS-CoV-2 vaccination and discuss our findings in the context of altered (auto)immunity following SARS-CoV-2 vaccination and/or infection.

Tolvaptan is the first orally active vasopressin receptor 2 antagonist approved by FDA in 2009 for the treatment of clinically significant hypervolemic and euvolemic hyponatremia associated with heart failure, syndrome of inappropriate antidiuretic hormone secretion, liver cirrhosis. Binding of vasopressin to V2 receptors which are located on renal collecting duct cells were competitively inhibited by Tolvaptan thus prevents vasopressin-mediated activation of these receptors and leads to an increase in the water permeability of the collecting duct causing an increase in the concentration of urine, results in an increase in free water clearance, a decrease in urine osmolality and a fall in serum sodium concentration. Tolvaptan is different from other conventional diuretics because it does not stimulate the sodium channel and increases free water excretion without affecting urinary sodium and potassium excretion. It is metabolized principally via the cytochrome P 450 (CYP 3A) isoenzymes and is eliminated by routes other than renal. Concurrent administration of tolvaptan with ketoconazole or other strong CYP 3A inhibitor decrease the total clearance of tolvaptan and increases tolvaptan concentrations. Urine sodium potassium ratio, weight loss, soluble CD14, urinary aquaporin 2 levels are known predictors of tolvaptan response. Tolvaptan is associated with decreased cost and high effectiveness.

Lifestyle interventions can have a positive impact on quality of life and psychological parameters in patients with metabolic syndrome (MetS). In this randomized controlled trial, 145 participants with MetS (62.8% women; 59.7 ± 9.3 years) were randomized to (1) 5-day fasting followed by 10 weeks of lifestyle modification (F + LM; modified DASH diet, exercise, mindfulness; n = 73) or (2) 10 weeks of lifestyle modification only (LM; n = 72). Outcomes were assessed at weeks 0, 1, 12, and 24, and included quality of life (Short-Form 36 Health Survey Questionnaire, SF-36), anxiety/depression (Hospital Anxiety and Depression Scale, HADS), stress (Cohen Perceived Stress Scale, CPSS), mood (Profile of Mood States, POMS), self-efficacy (General Self-Efficacy Scale, GSE), mindfulness (Mindfulness Attention Awareness Scale, MAAS), and self-compassion (Self-Compassion Scale, SCS). At week 1, POMS depression and fatigue scores were significantly lower in F + LM compared to LM. At week 12, most self-report outcomes improved in both groups—only POMS vigor was significantly higher in F + LM than in LM. Most of the beneficial effects within the groups persisted at week 24. Fasting can induce mood-modulating effects in the short term. LM induced several positive effects on quality of life and psychological parameters in patients with MetS.

BACKGROUND: Older adult patients are frequently referred to surgical services for the treatment of nonmelanoma skin cancer (NMSC). The appropriateness of offering surgery to patients with serious comorbidities and a limited life expectancy has been questioned in the literature. The purpose of this study was to determine the morbidity and 5-year mortality for patients with NMSC referred to the plastic surgery service. METHODS: A retrospective chart review was performed from July 1, 2011, to June 30, 2015, of all plastic surgery service consults for the treatment of NMSC. We collected the following data: age and life-limiting comorbidities at the time of referral, treatment, complications, and 5-year mortality. A χ(2) analysis was used to determine the statistical significance (P < .05) between the individual risk factors and 5-year mortality. The relative risk of 5-year mortality was calculated combining advanced age with individual comorbidities. RESULTS: The plastic surgery service completed 800 consults for NMSC over a 4-year period. Five-year mortality was 28.6%. Median age of patients deceased at 5 years was 78 years at the time of the consult submission. The surgical complication rate was 5%. Aged ≥ 80 years, coronary artery disease, congestive heart failure, cerebral vascular disease, peripheral vascular disease, dementia, chronic kidney disease, chronic obstructive pulmonary disease, and diabetes mellitus were found individually to be statistically significant predictors of 5-year mortality. Combining aged ≥ 80 years, coronary artery disease, congestive heart failure, or dementia increased the 5-year mortality to a relative risk > 3. CONCLUSIONS: Surgical excision of NMSC in older adult patients is indicated in most situations. A frank discussion with the patient and caregiver is suggested. Surgical treatment of NMSC in older adult patients has a low morbidity but needs to be balanced against a patient’s quality of life when they present with life-limiting comorbidities.

Background: Lifestyle interventions, such as fasting, diet, and exercise, are increasingly used as a treatment option for patients with metabolic syndrome (MS). This study assesses the efficacy and safety of fasting followed by lifestyle modification in patients with MS compared to lifestyle modification only. Methods: Single-blind, multicenter, parallel, randomized controlled trial in two German tertiary referral hospitals in metropolitan areas. Interventions: (a) 5-day fasting followed by 10 weeks of lifestyle modification (modified DASH diet, exercise, mindfulness; n = 73); (b) 10 weeks of lifestyle modification only (n = 72). Main outcomes and measures: Co-primary outcomes were ambulatory systolic blood pressure and the homeostasis model assessment (HOMA) index at week 12. Further outcomes included anthropometric, laboratory parameters, and the PROCAM score at weeks 1, 12, and 24. Results: A total of 145 patients with metabolic syndrome (62.8% women; 59.7 ± 9.3 years) were included. No significant group differences occurred for the co-primary outcomes at week 12. However, compared to lifestyle modification only, fasting significantly reduced HOMA index (Δ = −0.8; 95% confidence interval [CI] = −1.7, −0.1), diastolic blood pressure (Δ = −4.8; 95% CI = −5.5, −4.1), BMI (Δ = −1.7; 95% CI = −2.0, −1.4), weight (Δ = −1.7; 95% CI = −2.0, −1.4), waist circumference (Δ = −2.6; 95% CI = −5.0, −0.2), glucose (Δ = −10.3; 95% CI = −19.0, −1.6), insulin (Δ = −2.9; 95% CI = −5.3, −0.4), HbA1c (Δ = −0.2; 95% CI = −0.4, −0.05;), triglycerides (Δ = −48.9; 95% CI = −81.0, −16.9), IL−6 (Δ = −1.2; 95% CI = −2.5, −0.005), and the 10-year risk of acute coronary events (Δ = −4.9; 95% CI = −9.5, −0.4) after week 1. Fasting increased uric acid levels (Δ = 1.0; 95% CI = 0.1, 1.9) and slightly reduced eGRF (Δ = −11.9; 95% CI = −21.8, −2.0). Group differences at week 24 were found for weight (Δ = −2, 7; 95% CI = −4.8, −0.5), BMI (Δ = −1.0; 95% CI = −1.8, −0.3), glucose (Δ = −7.7; 95% CI = −13.5, −1.8), HDL (Δ = 5.1; 95% CI = 1.5, 8.8), and CRP (Δ = 0.2; 95% CI = 0.03, 0.4). No serious adverse events occurred. Conclusions: A beneficial effect at week 24 was found on weight; fasting also induced various positive short-term effects in patients with MS. Fasting can thus be considered a treatment for initializing lifestyle modification for this patient group; however, it remains to be investigated whether and how the multilayered effects of fasting can be maintained in the medium and longer term.

ZusammenfassungDie Diagnose Krebs bedeutet für die Betroffenen in der Regel einen massiven Einschnitt in ihr Leben, der mit Angst, Verunsicherung und Verlust an Lebensqualität einhergeht. Die psychische Belastung ist vor allem im Zeitraum zwischen Diagnose und Behandlungsbeginn sehr ausgeprägt mit deutlichen Auswirkungen auf den weiteren Krankheitsverlauf. Aktuelle Daten geben Hinweise darauf, dass es sinnvoll ist, schon frühzeitig resilienzfördernde therapeutische Interventionen in die Behandlung onkologischer Patienten zu integrieren. Interventionen aus dem Bereich der Mind-Body-Medizin (MBM), die in Kombination mit naturheilkundlichen Therapieansätzen im Rahmen einer integrativ-onkologischen Behandlung zunehmend Verbreitung auch im akutmedizinischen Bereich finden, können hier die psychoonkologische Versorgung effektiv ergänzen.

The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data, while N = 415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate.

BACKGROUND AND PURPOSE Patent foramen ovale (PFO)is associated with cryptogenic stroke, especially in young adults. Transcranial Doppler (TCD) ultrasound is used as a screening tool before transesophageal echocardiography (TEE). However, the use of Valsalva maneuver (VM) to identify a right-to-left-shunt underlies interindividual variability. Here, we aimed to assess whether a pressure-controlled standardization of VM is useful to estimate PFO size. METHODS We included patients aged 18-80 years with a PFO according to TEE. Subjects underwent TCD with microembolic signals (MES) counted under four pressure conditions (i.e., at rest, 15 mbar, 40 mbar, and maximum expiratory pressure). Findings were correlated with TEE-based PFO size. The predictive value of TCD at rest and VM-based TCD for PFO size estimation was assessed by stepwise multivariate linear regression models and multiple cross-tab-analyses. RESULTS We screened 203 subjects after a cerebrovascular event, of which 78 (48 males [61.5%], median age 55 years [22-80]) with PFO were included. We found an association between MES count and expiratory pressure (p < .001). Predefined MES count categories at TCD pressure conditions correlated significantly with PFO size measured by TEE. We propose a PFO size estimation model based on TCD at rest and under VM, which classified PFO size correctly in 64.1% with the highest accuracy for small PFOs. CONCLUSION Our data provide evidence that TCD with step-wise barometric standardization allows an estimation of PFO size with good accuracy. Though TCD will not replace TEE in future, this might be of clinical value in circumstances where TEE cannot be easily performed.

Background: Patients with cancer receiving tumor therapy often suffer from oral mucositis. Objectives: The aim of this project was to summarize experiences with nursing procedures by experts in integrative oncology and to establish recommendations for nursing interventions that can prevent or cure mucositis. Methods: The study design was an interdisciplinary consensus process based on a systematic literature search. Results: The panel discussed and agreed on 19 nursing procedures, which included mouthwashes, such as teas, supplements, oil applications, and different kinds of ice cubes to suck, as well as flaxseed solution, propolis, and mare milk. Twelve interventions were classified as effective, with effectiveness for OraLife, propolis, sea buckthorn pulp oil, marshmallow root tea also for xerostomia, Helago chamomile oil, mare milk, and Saliva Natura rated as highly effective in clinical experience. In the systematic literature search, a total of 12 out of 329 randomized controlled trials and meta-analyses on chamomile (n = 3), Calendula (n = 1) and sage (n = 1), propolis (n = 2), and sucking ice cubes (cryotherapy; n = 5) met all inclusion criteria. Trial evidence for effectiveness in oral mucositis was revealed for propolis and cryotherapy. Conclusions: The current evidence supports the use of some nursing procedures (f.e. propolis for 2 and 3 grade mucositis) for improving oral mucositis during cancer therapies. There is still a need to define general clinical practice guidelines for the supportive treatment of mucositis, as well as for more interdisciplinary research in this area.

Coronavirus disease (COVID-19)-associated mucormycosis (CAM) is an emerging threat globally, especially in India. More than 40,000 CAM cases have been reported in India. The emergence of CAM cases in India has been attributed to environmental, host, and iatrogenic factors. Mucorales spore burden has been reported globally; however, their presence is higher in tropical countries such as India, contributing to the emergence of CAM. Before the COVID-19 pandemic, patients with diabetes mellitus, haematological malignancies, solid organ transplants, corticosteroid therapy and neutropenia were more prone to mucormycosis, whereas in COVID-19 patients, virus-induced endothelial dysfunction, hyperglycaemia, and immune dysfunction following corticosteroid use increase the risk of acquiring mucormycosis. The interaction of Mucorales spores with the epithelial cells, followed by endothelial invasion, is a crucial step in the pathogenesis of mucormycosis. Endothelial damage and increased endothelial receptor expression induced by COVID-19 infection may predispose patients to CAM. COVID-19 infection may directly induce hyperglycaemia by damaging beta cells of the pancreas or by corticosteroid therapy, which may contribute to CAM pathogenesis. Iron acquisition from the host, especially in diabetic ketoacidosis (DKA) or deferoxamine therapy, is an important virulence trait of Mucorales. Similarly, the hyperferritinaemia caused by COVID-19 may act as a source of iron for Mucorales growth and invasion. In addition, corticosteroid treatment reduces or abolishes the innate immune functions of phagocytic cells contributing to the pathogenesis of CAM. This review aims to discuss primarily the host and iatrogenic factors shared between COVID-19 and mucormycosis that could explain the emergence of CAM.

Background: Breast cancer is one of the leading cancers in women in the Western world. Cancer treatment, especially chemotherapy, is often associated with physical and psychosocial side effects. Objective: To improve the quality of life and manage side effects, a new integrative mind-body-medicine group concept for breast cancer patients receiving chemotherapy was developed and pilot tested. Methods: Breast cancer patients participated in a 66 hours mind-body-medicine group program tailored to the needs of cancer patients during chemotherapy. The program was integrated into standard care encompassing mindfulness training, yoga, moderate exercise, nutrition, complementary self-help strategies, cognitive restructuring, and acupuncture. Quality of life (EORTC QLQ-C30), depression and anxiety (HADS), stress (PSS-10), and fatigue (BFI) were assessed before and after the program, as well as satisfaction and safety. Analyses were carried out on exploratory basis with paired samples t-tests. Results: Fifty-seven female patients, aged 51.3±10.5 years, with breast cancer diagnoses were enrolled. After completing the program, global EORTC quality of life was improved (D=9.5; 95%-CI=[2.9|16.1]; p=.005), although the EORTC-symptom scales assessing fatigue (D=9.9; 95%-CI=[1|18.8]; p=.030), nausea (D=7.1; 95%- CI=[0.6|13.6]; p=.031), and dyspnea (D=12.5; 95%-CI=[2.9|22.1]; p=.011) were found to be increased. Stress (D=-3.5; 95%-CI=[-5|-2.1]; p=.000), anxiety (D=-3.8; 95%-CI=[-4.9|-2.7]; p=.000) and depression (D=-3.9; 95%-CI=[-4.9|-2.8]; p=.000) were also found to be significantly reduced. Regarding the severity of (D=0.2; 95%- CI=[-0.8|0.5]; p=.644) and the impairment due to fatigue (D=0.1; 95%-CI=[-0.8|0.6]; p=.696), no significant worsening was observed. Patients were satisfied with the program. No serious adverse events were reported. Conclusion: Breast cancer patients benefit from an integrative mind-body-medicine group program during chemotherapy regarding the quality of life and psychological symptoms. Randomized controlled trials are warranted.

Purpose The aim of the present cross-sectional real-world study is to evaluate the impact of switch of anti-VEGF agent from ranibizumab to aflibercept on visual acuity, treatment frequency and retinal morphology after 12 months in eyes with ongoing chronic treatment for wet age-related macular degeneration (AMD) compared to eyes not subjected to switch of anti-VEGF agent. Methods Data was obtained retrospectively from the Swedish Macular Register, spectral-domain optical coherence tomography (OCT) images and electronic patient charts. All eyes included were treated in the same clinical setting at the Department of Ophthalmology at the county hospital of Västmanland in Västerås, Sweden. Results In total, 282 and 359 eyes were included in the non-switch and switch cohorts, respectively. The cohorts were well balanced. Visual acuity remained stable during the observation period in both cohorts of eyes. The number of anti-VEGF treatments slowly declined over time in both cohorts of eyes and, consequently, the treatment intervals increased during the observation period. In eyes subjected to switch of anti-VEGF agent, planned treatment interval at 12 months was 7.6 (mean; SD 2.9) weeks compared to 6.8 (mean; SD 2.7) in the non-switch cohort (P = 0.001). OCT images demonstrated lower prevalence of intraretinal and subretinal fluid as well as pigment epithelial detachment at 12 months in eyes subjected to switch of anti-VEGF agent compared to non-switch eyes. Conclusion Switch of anti-VEGF agent from ranibizumab to aflibercept did not affect visual function whereas improvement in retinal morphology was observed. These findings suggest a beneficial effect of switching from ranibizumab to aflibercept in eyes with ongoing chronic anti-VEGF treatment irrespective of previous response to ranibizumab. Longer follow-up is required to further evaluate the potential clinical significance of this finding.

Patients with ulcerative colitis suffer from impaired health-related quality of life (HrQoL). Comprehensive lifestyle-modification might increase HrQoL and decrease disease activity. Ninety-seven patients in clinical remission with impaired HrQoL were randomly assigned to a 10 week comprehensive lifestyle-modification program (LSM, n = 47, 50.28 &plusmn, 11.90 years) or control (n = 50, 45.54 &plusmn, 12.49 years) that received a single workshop of intense training in naturopathic self-help strategies. Primary outcome was HrQoL (Inflammatory Bowel Disease Questionnaire, IBDQ) at week 12. Secondary outcomes included IBDQ subscales, generic HrQoL, disease activity and microbiome. Both groups showed improvement in HrQoL from baseline to post-treatment at week 12. The IBDQ sum score showed no significant group difference (p = 0.251). If patients attended more than 50% of the training sessions, a significant group effect (p = 0.034) was evident in favor of LSM. In addition, the SF-36 mental component summary (p = 0.002) was significantly different between the groups in favor of LSM. Disease activity microbiome and adverse events did not differ. Both a single workshop and a 10-week comprehensive lifestyle-modification program can improve HrQoL in patients with ulcerative colitis in remission with no apparent effects on clinical disease activity. A treatment difference was observed when examining a subsample of patients who attended &ge, 50% of sessions.

Background Cancer registries usually assess data of conventional treatments and/or patient survival. Beyond that, little is known about the influence of other predictors of treatment response related to the use of complementary therapies (CM) and lifestyle factors affecting patients’ quality and quantity of life. Methods INTREST is a prospective cohort study collecting register data at multiple German certified cancer centers, which provide individualized, integrative, in- and outpatient breast cancer care. Patient-reported outcomes and clinical cancer data of anticipated N = 715 women with pTNM stage I-III breast cancer are collected using standardized case report forms at the time of diagnosis, after completing neo−/adjuvant chemotherapy, after completing adjuvant therapy (with the exception of endocrine therapy) as well as 1, 2, 5, and 10 years after baseline. Endpoints for multivariable prediction models are quality of life, fatigue, treatment adherence, and progression-based outcomes/survival. Predictors include the study center, sociodemographic characteristics, histologic cancer and comorbidity data, performance status, stress perception, depression, anxiety, sleep quality, spirituality, social support, physical activity, diet behavior, type of conventional treatments, use of and belief in CM treatments, and participation in a clinical trial. Safety is recorded following the Common Terminology Criteria for Adverse Events. Discussion This trial is currently recruiting participants. Future analyses will allow to identify predictors of short- and long-term response to integrative breast cancer treatment in women, which, in turn, may improve cancer care as well as quality and quantity of life with cancer. Trial registration German Clinical Trial Register DRKS00014852. Retrospectively registered at July 4th, 2018.

Komplementarmedizin wird im Sinne einer integrativen Onkologie erganzend zur konventionellen Medizin eingesetzt und grenzt sich damit ab von der sog. Alternativmedizin, die anstelle der etablierten Medizin zum Einsatz kommt. Von der alternativen Therapie des Mammakarzinoms wird wegen eines erhohten Mortalitatsrisikos abgeraten. Uber die Leitlinien der SIO (Society for Integrative Oncology) und die Therapieempfehlungen der AGO (Arbeitsgemeinschaft Gynakologische Onkologie e. V.) sowie die Website des Memorial Sloan Kettering Cancer Center konnen fundierte Informationen zu komplementarmedizinischen Verfahren eingeholt werden. Evidenz zur Therapie von Insomnie, Angst/Stress und Fatigue besteht fur Verfahren der Mind-Body-Medizin (MBM, z. B. Ausdauer- und Krafttraining, MBSR [Mindfulness Based Stress Reduction] und Yoga). Zur Therapie der Fatigue konnen daruber hinaus Akupunktur und Akupressur in Erwagung gezogen werden, wahrend von der Gabe von Acetyl-L-Carnitin abgeraten wird. Stressbelastungen und Insomnie sollten aufgrund der prognostischen Relevanz fruhzeitig erfasst und behandelt werden.

Mind-Body-Medizin ist ein Teil der Komplementarmedizin. Im Gegensatz zur Konzentration auf die Erkrankung in der Schulmedizin liegt bei der Mind-Body-Medizin der Fokus darauf, Gesundheit zu entwickeln und zu erhalten. Eingesetzte Verfahren sind unter anderem Yoga, progressive Muskelrelaxation und Meditation.

Einleitung: Die Diagnose und Behandlung von Krebserkrankungen gehen häufig mit körperlichen und psychosozialen Beeinträchtigungen einher. Viele Krebspatienten wünschen Komplementärmedizin wie z.B. die Mind Body Medicine. Konzept: Die Klinik für Naturheilkunde und Integrative Medizin an den Kliniken Essen-Mitte bietet Mind Body Medicine, basierend auf dem «Mindfulness-Based Stress Reduction Program» (Stressreduktion durch Achtsamkeit) und dem Mind-Body-Krebsmedizinprogramm des Harvard Mind-Body Medical Institute, im Rahmen einer Tagesklinik für Krebspatienten an. Das Programm umfasst Achtsamkeitstraining, Yoga, achtsame Körperübungen, Ernährung, naturheilkundliche Selbsthilfestrategien und kognitive Umstrukturierungen. Fälle: Zwei Patientinnen, die an dem Tagesklinikprogramm teilgenommen haben, werden vorgestellt. Eine Patientin litt an Angst und Depressivität nach einer kürzlich diagnostizierten Brustkrebserkrankung, die andere an psychischen Beeinträchtigungen infolge mehrfacher Exzisionen von Nävi nach chirurgischer Entfernung eines malignen Melanoms. Bei beiden Patientinnen war Besserung im Hinblick auf Angst und weitere psychische Symptome festzustellen. Schlussfolgerung: Das onkologisch-naturheilkundliche Mind Body Medicine-Programm an den Klinischen Essen-Mitte scheint psychische Folgen von Krebs und seiner Behandlung zu lindern. Weitere Untersuchungen und randomisierte kontrollierte Studien sind notwendig, um diese Ergebnisse zu bestätigen. Übersetzung aus Integrative Cancer Therapies 2013;12:503-507

Die Mind-Body-Medizin (MBM) nutzt gezielt die Interaktion zwischen Psyche, Korper und Verhalten, um somatische Erkrankungen und deren psychische Begleitsymptomatik supportiv zu behandeln. In der Onkologie fokussiert die MBM auf die Reduktion von Begleitsymptomen und Nebenwirkungen der kurativen oder adjuvanten Therapie. Zahlreiche Verfahren der MBM sind mittlerweile in wissenschaftlichen Studien evaluiert worden. So zeigten Metaanalysen, dass „mindfulness-based stress reduction“, ein achtsamkeitsbasiertes Gruppenprogramm, eine signifikante positive Wirkung auf Lebensqualitat, Fatigue, Schlafstorungen, Stress, Angst und Depressivitat bei Frauen mit Mammakarzinom ausubt. Ahnliches gilt fur Yoga: Ein aktueller Cochrane-Review fand positive Wirkungen auf Lebensqualitat und korperliche wie psychische Symptomatik bei Frauen mit Mammakarzinom. Die Wirkungen beider Methoden bei anderen Tumorentitaten sind jedoch unklar. Hypnotherapie reduzierte in randomisierten Studien Schmerz und Stress im Zusammenhang mit Brustbiopsien oder Lumpektomien sowie padiatrischen Lumbalpunktionen. Daneben finden sich positive Wirkungen auf mit Radiotherapie assoziierter Fatigue sowie menopausale Symptome bei Frauen unter antihormoneller Therapie. Die MBM kann insbesondere als multimodales Programm in die supportive Onkologie integriert werden. Im Rahmen klinischer Studien zeigten solche Programme positive Wirkungen auf korperliche und psychische Symptomatik bei gemischten onkologischen Patientengruppen. Da alle Einzelinterventionen sowie multimodale Programme effektiv und auch sicher zu sein scheinen, kann die MBM als sinnvolle supportive Erganzung in der Onkologie berucksichtigt werden.

Theoretical models of dopamine function stemming from reinforcement learning theory have emphasized the importance of prediction errors, which signal changes in the expectation of impending rewards. Much less is known about the effects of mean reward rates, which may be of motivational significance due to their role in computing the optimal effort put into exploiting reward opportunities. Here, we used a reinforcement learning model to design three functional neuroimaging studies and disentangle the effects of changes in reward expectations and mean reward rates, showing recruitment of specific regions in the brainstem regardless of prediction errors. While changes in reward expectations activated ventral striatal areas as in previous studies, mean reward rates preferentially modulated the substantia nigra/ventral tegmental area, deep layers of the superior colliculi, and a posterior pontomesencephalic region. These brainstem structures may work together to set motivation and attentional efforts levels according to perceived reward opportunities.

Background To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort. Methods Patient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients. Results 14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course. Conclusion A small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.

© 2019 The Author(s). Background: Distortion of taste sensations is a common chemotherapy-induced side effect; however, treatment evidence is limited. Pilot data indicated that acupuncture might be able to improve symptoms of dysgeusia. Thus, the aim of this study is to investigate the effects and side effects of hypoglossal acupuncture in the treatment of dysgeusia in patients with breast cancer undergoing chemotherapy. Methods/design: The study is a randomized controlled trial comparing a single verum acupuncture treatment with two active comparators: sham acupuncture and dietary recommendations. Sample size calculation revealed a total of 75 patients pending an alpha of 0.05, a power of 0.8, and an estimated effect size of 0.80. Patients with breast cancer undergoing platinum- or taxane-based chemotherapy will be included if they present with phantogeusia (abnormal taste sensations without an external oral stimulus) with an intensity of 4 points or above on an 11-point numeric rating scale (NRS). The primary outcome is phantogeusia; secondary outcomes include parageusia (abnormal taste of food), hypogeusia (reduced taste sensations), hypergeusia (increased taste sensations), xerostomia (dry mouth), stomatitis, appetite, and functional impairment. All outcomes will be assessed at baseline and prior to the next chemotherapy administration using an 11-point NRS for each. All adverse events will be recorded. Discussion: The results of this study will demonstrate the extent to which hypoglossal acupuncture may influence the intensity of and functional impairment due to chemotherapy-induced dysgeusia. Trial registration: Clinical Trials.gov, NCT02304913. Registered on 19 November 2014.