Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[Discontinuation of Chromium-51 for clinical use: What are the possible alternatives for radiopharmacies and nuclear medicine departments?] / Arrêt de production du chrome-51 (51Cr) a usage clinique : quelles alternatives possibles pour les services de radiopharmacie et de médecine nucléaire ?

OBJECTIVES: Last October, the nuclear medicine departments were informed of the closure of the chromium-51 production line for clinical use. This radionuclide has different diagnostic indications in nephrology and hematology. It was therefore essential to set up alternative exploration protocols to overcome this production stoppage. METHODS: Chromium-51 EDTA has been replaced by technetium-99m DTPA for the determination of glomerular filtration rates. Sodium chromate was substituted by sodium pertechnetate for the determination of globular volumes. A retrospective analysis of the chromium-51 data was performed followed by a prospective study, from January to December 2019 for technetium tracers. RESULTS: One hundred and forty-four patients were included in the study. Forty-two EDTA-51Cr and 30 DTPA-99mTc exams were conducted and compared. There were no significant differences between the methods used to assess renal function (P=0.355). For the determination of blood cell and plasma volumes, 47 tests with 51Cr and 125I and 25 tests with 99mTc and 125I were performed and compared. There were no significant differences in the determination of total (P=0.325) and globular (P=0.148) volumes. CONCLUSIONS: The study carried out shows that there is no significant difference between the results obtained with chromium-51 and technetium tracers. As a result, clinical activity was maintained in good conditions.

[Yoga for mental disorders]. / Yoga bei psychischen Störungen.

BACKGROUND: The demand for complementary clinically efficacious, safe, patient acceptable, and cost-effective forms of treatment for mental illness is growing. Yoga has beneficial effects on somatic and mental health factors; therefore, yoga has preventive and therapeutic capabilities to improve mental dysfunction. OBJECTIVE: In this overview of the current literature, the evidence of the effects of yoga on selected major psychiatric disorders is summarized. RESULTS: The strongest evidence base for yoga exists in reducing depressive symptoms but its use in major depressive disorders is less clear. The evidence for the efficacy of yoga for anxiety disorders, and posttraumatic stress disorder (PTSD) is encouraging, but not definitive due to only a few randomized controlled trials and methodological problems. CONCLUSION: There is preliminary evidence that meditation-based yoga interventions may be helpful for depression, anxiety and PTSD; however, there may also be the risk of engaging in extreme yoga practices. The value of integrating yoga into a treatment plan for patients with psychiatric disorders needs to be evaluated on an individual basis. Healthcare providers can motivate and help patients evaluate whether a given yoga class is helpful and safe for them. Methodological problems and the unclear risk-benefit ratio preclude definitive recommendations for yoga as an adjunct treatment.

[Melasma : An update on the clinical picture, treatment, and prevention]. / Melasma : Ein Update zu Klinik, Therapie und Prävention.

Melasma, also known as chloasma or mask of pregnancy, presents clinically as hyperpigmented skin areas, which develop mostly in the face as a consequence of increased synthesis of melanin. The established treatment options, including topically applied agents and the use of various laser systems, mostly result in improvement but not in complete remission of the lesions. Because of its significant impact on quality of life and the limited effectivity of available treatment options, the management of melasma is challenging for the treating physician. Although many risk factors, including pregnancy and UV exposure, have been identified, the pathogenesis is not yet fully understood. Avoiding solar or artificial UV exposure is of high importance both for the prevention of melasma and for the clinical outcome of existing lesions. In order to avoid vitamin D deficiency, oral vitamin D supplementation should be recommended. In this review, we give an update on clinical aspects, epidemiology, pathogenesis and therapy of melasma and give an outlook on future developments.

Effect of dietary fish oil on the expression of genes involved in lipid metabolism in liver and skeletal muscle of lactating sows.

This study investigated the hypothesis that dietary supplementation of fish oil as a source of n-3 polyunsaturated fatty acids (PUFA) influences the expression of target genes of sterol regulatory element-binding proteins (SREBP)-1 and (SREBP)-2 involved in triacylglycerol (TAG) synthesis and fatty acid and cholesterol metabolism in the liver, and moreover activates the expression of target genes of peroxisome proliferation-activated receptor (PPAR)-α involved in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating sows were fed a control diet or a fish oil diet with either 50 g of a mixture of palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish oil group contained 19.1 g of n-3 PUFA (mainly 20:5 n-3 and 22:6 n-3) per 100 g of total fatty acids, while the diet of the control group contained 2.4 g of n-3 PUFA (mainly 18:3 n-3) per 100 g of total fatty acids. The fish oil group had reduced relative mRNA concentrations of various target genes of SREBP-1 involved in fatty acid and TAG synthesis in comparison with the control group (p < 0.05). Relative mRNA concentrations of target genes of PPARα involved in fatty acid catabolism in both liver and muscle, and mRNA concentrations of target genes of SREBP-2 involved in cholesterol synthesis and uptake were not influenced by fish oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content of milk and weight gains of litters during the suckling period were not different between the two groups of sows. In conclusion, this study suggests that fish oil has only minor effects on hepatic lipid metabolism, which are non-critical with respect to milk production in sows.

Synergistic effects of diet and exercise on hippocampal function in chronically stressed mice.

Severe chronic stress can have a profoundly negative impact on the brain, affecting plasticity, neurogenesis, memory and mood. On the other hand, there are factors that upregulate neurogenesis, which include dietary antioxidants and physical activity. These factors are associated with biochemical processes that are also altered in age-related cognitive decline and dementia, such as neurotrophin expression, oxidative stress and inflammation. We exposed mice to an unpredictable series of stressors or left them undisturbed (controls). Subsets of stressed and control mice were concurrently given (1) no additional treatment, (2) a complex dietary supplement (CDS) designed to ameliorate inflammation, oxidative stress, mitochondrial dysfunction, insulin resistance and membrane integrity, (3) a running wheel in each of their home cages that permitted them to exercise, or (4) both the CDS and the running wheel for exercise. Four weeks of unpredictable stress reduced the animals' preference for saccharin, increased their adrenal weights and abolished the exercise-induced upregulation of neurogenesis that was observed in non-stressed animals. Unexpectedly, stress did not reduce hippocampal size, brain-derived neurotrophic factor (BDNF), or neurogenesis. The combination of dietary supplementation and exercise had multiple beneficial effects, as reflected in the number of doublecortin (DCX)-positive immature neurons in the dentate gyrus (DG), the sectional area of the DG and hippocampal CA1, as well as increased hippocampal BDNF messenger ribonucleic acid (mRNA) and serum vascular endothelial growth factor (VEGF) levels. In contrast, these benefits were not observed in chronically stressed animals exposed to either dietary supplementation or exercise alone. These findings could have important clinical implications for those suffering from chronic stress-related disorders such as major depression.

[Quality of life after multiple trauma]. / Lebensqualität nach Polytrauma.

BACKGROUND: Multiple trauma is an independent injury pattern which, because of its complexity, is responsible for 25 % of the costs for the treatment of all injured patients. Because of the often long-lasting physical impairment and the high incidence of residual permanent handicaps, it is apparent that multiple trauma can lead to a reduction in patient quality of life. OBJECTIVES: The aim of this study was to give an overview of the known data concerning the change in quality of life for multiple trauma patients. Furthermore, predictors for the reduction of quality of life after multiple trauma will be identified. MATERIALS AND METHODS: A MedLine search was performed to identify studies dealing with the outcome after multiple trauma. RESULTS: In addition to functional outcome parameters, the term quality of life has become more important in recent years when it comes to evaluating the outcome following injury. While the mortality after multiple trauma could be significantly reduced over the years, there is no comparable effect on the quality of life. Predictors for a worse quality of life after multiple trauma are female gender, high age, low social status, concomitant head injuries and injury to the lower extremities. CONCLUSION: The fact that mortality after multiple trauma has decreased but not impairment of the quality of life makes it clear that in addition to the acute medical treatment, a follow-up treatment including not only physiotherapy but also psychotherapy is crucial for multiple trauma patients.

British Dietetic Association evidence-based guidelines for the dietary management of Crohn's disease in adults.

BACKGROUND: Crohn's disease is a debilitating chronic inflammatory bowel disease. Appropriate use of diet and nutritional therapy is integral to the overall management strategy of Crohn's disease. The aim was to develop evidence-based guidelines on the dietary management of Crohn's disease in adults. METHODS: Questions relating to the dietary management of Crohn's disease were developed. These included the roles of enteral nutrition to induce remission, food re-introduction diets to structure food re-introduction and maintain remission, and dietary management of stricturing disease, as well as whether probiotics or prebiotics induce or maintain remission. A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic database search engines CINAHL, Cochrane Library, EMBASE, MEDLINE, Scopus and Web of Science. Evidence statements, recommendations, practical considerations and research recommendations were developed. RESULTS: Fifteen research papers were critically appraised and the evidence formed the basis of these guidelines. Although corticosteroids appear to be more effective, enteral nutrition (elemental or non-elemental) can be offered as an alternative option to induce disease remission. After a course of enteral nutrition, food re-introduction diets may be useful to structure food re-introduction and help maintain disease remission. Dietary fibre is contraindicated in the presence of strictures as a result of the risk of mechanical obstruction. The use of probiotics and prebiotics is not currently supported. CONCLUSIONS: As an alternative to corticosteroids, evidence supports enteral nutrition to induce disease remission. Food re-introduction diets provide structure to food re-introduction and help maintain disease remission. These guidelines aim to reduce variation in clinical practice.

Genotype and phenotype correlations in 417 children with congenital hyperinsulinism.

CONTEXT: Hypoglycemia due to congenital hyperinsulinism (HI) is caused by mutations in 9 genes. OBJECTIVE: Our objective was to correlate genotype with phenotype in 417 children with HI. METHODS: Mutation analysis was carried out for the ATP-sensitive potassium (KATP) channel genes (ABCC8 and KCNJ11), GLUD1, and GCK with supplemental screening of rarer genes, HADH, UCP2, HNF4A, HNF1A, and SLC16A1. RESULTS: Mutations were identified in 91% (272 of 298) of diazoxide-unresponsive probands (ABCC8, KCNJ11, and GCK), and in 47% (56 of 118) of diazoxide-responsive probands (ABCC8, KCNJ11, GLUD1, HADH, UCP2, HNF4A, and HNF1A). In diazoxide-unresponsive diffuse probands, 89% (109 of 122) carried KATP mutations; 2% (2 of 122) had GCK mutations. In mutation-positive diazoxide-responsive probands, 42% were GLUD1, 41% were dominant KATP mutations, and 16% were in rare genes (HADH, UCP2, HNF4A, and HNF1A). Of the 183 unique KATP mutations, 70% were novel at the time of identification. Focal HI accounted for 53% (149 of 282) of diazoxide-unresponsive probands; monoallelic recessive KATP mutations were detectable in 97% (145 of 149) of these cases (maternal transmission excluded in all cases tested). The presence of a monoallelic recessive KATP mutation predicted focal HI with 97% sensitivity and 90% specificity. CONCLUSIONS: Genotype to phenotype correlations were most successful in children with GLUD1, GCK, and recessive KATP mutations. Correlations were complicated by the high frequency of novel missense KATP mutations that were uncharacterized, because such defects might be either recessive or dominant and, if dominant, be either responsive or unresponsive to diazoxide. Accurate and timely prediction of phenotype based on genotype is critical to limit exposure to persistent hypoglycemia in infants and children with congenital HI.

Potential interactions of complementary and alternative medicine with cancer therapy in outpatients with gynecological cancer in a comprehensive cancer center.

PURPOSE: About 40-50 % of cancer patients use complementary and alternative medicine (CAM). Women, and especially those with gynecological cancers, are more active in this field than men. The goal of our study was to estimate the likelihood of CAM use and the likelihood of interactions of CAM with cancer therapy in the setting of a gynecological outpatient clinic at a German Comprehensive Cancer Center (CCC). METHODS: One hundred consecutive gynecological outdoor patients of the CCC in Frankfurt am Main in Germany were interviewed with a standardized questionnaire on CAM use. An investigation on potential interactions was done by matching a scientific database systematically. RESULTS: Sixty-nine of the interviewed 100 women received chemotherapy, 23 endocrine therapy and 41 monoclonal antibodies. In total, 64 % used CAM, 48 % used at least one substance-bound CAM. In 17 out of those 48 cases (35 %), interactions were unlikely, whereas they were probable in 14 patients (29 %). Thus, a third of all patients in this study were in danger of interactions. More than half of all CAM users and three quarters of users of substance-bound CAM are at risk of interactions. This number is independent of whether the patient is taking chemotherapy, endocrine therapy or antibodies. CONCLUSIONS: The frequency of CAM use we found is in line with international data from CCCs in the USA. To our knowledge, this is the first study publishing data on the frequency of potential interactions. Thus, an initiative to protect women from the dangers of uncontrolled CAM use is urgently needed. In the discussion, we propose a concept of how to achieve this aim.

Tolerability of a new fast updosed immunologically enhanced subcutaneous immunotherapy formulation with an optimized allergen to adjuvant ratio under routine practice conditions: a noninterventional observational study.

BACKGROUND AND OBJECTIVES: A fast updosed immunologically enhanced subcutaneous immunotherapy (SCIT) formulation with an optimized allergen to aluminium hydroxide ratio was first introduced in September 2009 in Germany. A large randomized controlled trial showed that the formulation had considerable immunologic effects and good tolerability. In this open-label, uncontrolled, noninterventional study, tolerability was investigated during routine application. PATIENTS AND METHODS: Patients with allergic rhinoconjunctivitis and/or asthma were treated with pollen and mite allergens using a 5-injection updosing schedule (AVANZ: 300, 600, 3000, 6000 and 15 000 SQ+ units) with weekly intervals, followed by a maintenance schedule with injections of 15,000 SQ+ units.Adverse events (AEs) were recorded by physicians, and symptoms and use of symptomatic medication were analyzed before the start of therapy and after an average 8-month treatment period. RESULTS: SCIT was documented by 362 allergists in 1036 patients between September 2009 and February 2011. AEs mainly consisted of local reactions during updosing (in 24.5% of patients). Systemic reactions were observed during updosing (8.4%) and maintenance therapy (1.7%), the most frequent of which was dyspnea. Overall, tolerability and the effect of treatment were rated as good or very good by 94.9% and 86.6% of patients and by 96.2% and 89.6% of physicians, respectively. CONCLUSIONS: In this open-label, noninterventional study, fast updosed immunologically enhanced SCIT (AVANZ) was well tolerated in a large group of patients.

[Fear of allowing sugar into the cell--case 05/2009. Comorbidity of diabetes mellitus and eating disorders]. / Von der Angst, den Zucker in die Zelle zu lassen - Fall 05/2009. Komorbidität von Diabetes mellitus und Essstörungen.

HISTORY AND ADMISSION FINDINGS: An 19-year-old female patient was admitted to our department of psychosomatic medicine and psychotherapy for the treatment of her metabolically deranged type 1 diabetes mellitus. INVESTIGATIONS: Exploration and assessment revealed a typical eating disorder symptomatology. The body mass index at time of admission was 18.7 kg/m (2). Episodes of binge eating were followed by purging behaviour (insulin purging, vomiting). DIAGNOSIS, TREATMENT AND COURSE: After diagnosis of bulimia nervosa, the patient was treated with a structured dual treatment regime consisting of psychosomatic/psychotherapeutic interventions and endocrinological support. The existing complex bio-psycho-social conditions were considered carefully. In the treatment course typical eating disorder behaviour (i. e. insulin purging) decreased and mood stabilised. CONCLUSIONS: Adolescent women with diabetes mellitus are at an increased risk of developing an eating disorder. This comorbidity is associated with a markedly increased mortality. Therefore, diagnosis of an eating disorder should be made as soon as possible in order to provide adequate treatment not only for the metabolic disturbances but also for the coexisting psychosomatic disorder.

[Impact of therapeutic riding on gait and posture regulation]. / Der Einfluss des Therapeutischen Reitens auf den Gang und die Haltungsregulation.

BACKGROUND: Hippotherapy has become an important therapeutic option in patients suffering from motoric dysfunction. The physiologic basis of this approach is the three-dimensional transmission of the horse's motion onto the patients body. These motion stimuli are believed to exert possitve effects on the patients's postural control systems. AIM: To test the hypothesis that hippotherapy has both positive short- and lang-term effects on gait and posture control of persons suffering from motoric disabilities. METHODS: Twenty-two children and adolescents aged 9.69 +/- 4.01 years (range: 9.69 +/- 4.01 years) with motoric dysfunctions were included in a prospective matched control study. In each participant, gait and posture control were investigated on four different occasions (O1 - O4) using the Interactive balance system (IBS; Tetrax Inc., Ramat Gan, Israel) and the portable gait analysis sytem RehaWatch (Hasomed, Magdeburg, Germany). The dates of gait and posture analysis were defined as follows: O 1: immediately prior to first therapeutic riding session (TRS); O 2: immediately after first TRS; O 3: after the last day of an eight weeks period of daily TRS; O 4: seven weeks later after a TRS free interval. RESULTS: The following parameters were slightly improved (adjusted significance level of p < 0.003) after eight weeks of therapeutic riding: (O1 vs. O 3): (1) walking distance (p = 0.009, eta(2) = 0.339); (2) pace frequency (p = 0.007, eta(2) = 0.358); (3) walking speed (p = 0.006, eta(2) = 0.367), and (4) time of attachment (p = 0.007, eta(2) = 0.360). The only short-term effect observed was a significant decrease of the attachment phase (p = 0.002, eta(2) = 0.387). Interestingly, gait symmetry remained unaffected. Posturography (adjusted significance level of p < 0.01) at O 1 versus O 2 (short-term) showed a significant decrease of the performance of both the visual-nigrostriatal subsystem (p < 0.001) and the somato-sensory subsystem (p = 0.001). At O 1 versus O 3 (long-term), the following parameters were sharply decreased: (1) postural stability (p = 0.011), and (2) somatosensory performance (p = 0.011). CONCLUSIONS: In the individuals investigated, an eight weeks series of therapeutic riding did not improve posture control and had only a small positive effect on gait performance. The reasons for these rather disappointing results could have been the low number of therapeutic riding sessions (0.5 sessions per week), and the relatively short duration (30 min) of each session. It remains to be seen, whether a higher density and longer duration of therapeutic riding sessions yields better results.

Successful autologous peripheral blood stem cell transplantation in a Jehovah's Witness with multiple myeloma: review of literature and recommendations for high-dose chemotherapy without support of allogeneic blood products.

We present a case report of a successful high-dose melphalan therapy and autologous stem cell transplantation without the use of allogeneic blood product support in a 70-year-old patient suffering from multiple myeloma. Based on the experience in this case and thorough evaluation of the literature, we consider pre-transplant Hb level of 11-12 g/dl, platelet count higher than 70/nl, good WHO performance status of two and lower and informed consent as important eligibility criteria. During cytopenia recommended supportive measures include growth factor support with erythropoietin and G-CSF, p.o. iron treatment as well as prophylactic use of anti-fibrinloytic agents. Furthermore we discuss additional options that might be considered depending on the individual factors as e.g. pre-transplant collection and cryoconservation of autologous platelet concentrates. Moreover, an analysis of socio-economic issues regarding this procedure is presented. We conclude that allogeneic blood product free transplantation is a feasible procedure that can be offered to the patients belonging to distinct religious groups refusing allogeneic blood products as Jehovás Witnesses and patients presenting other contraindications for transfusions.

[Obesity--an interdisciplinary task]. / Adipositas--eine interdisziplinäre Aufgabe.

In industrial nations, over the last five decades conditions concerning nutrition and physical exercise as well as socio-economic circumstances have changed radically. One of the consequences following from this development has been a rapid increase in the prevalence of obesity. Studies have shown that currently 20 percent of the German adult population suffer from obesity. Investigations into the etiology of obesity have to address complex interactions between genetic, socio-economic and psychosocial factors. A year ago, at the University Hospital Tübingen different departments joined to set up the "Plattform Adipositas". Endocrinologists, obesity surgeons, professionals in sports medicine and psychosomatic medicine as well as dieticians are collaborating to develop scientifically based therapy programs and treatment pathways for obese patients. The following article gives an account of this exemplary interdisciplinary cooperation.