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Unilateral aldosteronism may also be due to multiple CYP11B2-expressing nodules of various sizes or a continuous band of hyperplastic ZG cells expressing CYP11B2. Use of CYP11B2 antibodies to identify areas for sequencing has greatly facilitated the detection of aldosterone-driving mutations. © Georg Thieme Verlag KG Stuttgart · New York.in English, German HINTERGRUND Fragebögen ermöglichen die subjektive Bewertung des Hörens durch Patienten. Seit 2012 ist der APHAB-Fragebogen Bestandteil der Qualitätssicherungsvereinbarung (QSV) bei einer Hörgeräteversorgung (HGV) zwischen der Kassenärztlichen Bundesvereinigung (KBV) und dem Spitzenverband der gesetzlichen Krankenkassen. Die Verwendung der vereinbarten Formel zur Errechnung des Verbesserungsquotienten bewertet schlechte HGV überproportional gegenüber guten, was in der Gesamtbetrachtung zu Verzerrungen führt. Die bisherige Formel wurde in dieser Studie mit 2 Alternativen in ihrer Auswirkung verglichen. METHODE Anhand von 6861 Datensätzen von Patienten mit einer nach der HMR erfolgreich abgeschlossenen HGV aus einer APHAB-Datenbank wurden die Ergebnisse des Versorgungserfolgs des bisherigen Verbesserungsquotienten (A) mit denen eines alternativen (B) verglichen, der nach einer neuentwickelten Formel berechnet wurde. Zudem wurden die Ergebnisse nach A und B mit dem bisher ebenfalls schon außerhalb des QSV verwendeten kumulierten Gesamtnutzens verglichen. ERGEBNISSE Der Mittelwert lag für A für die Fälle mit negativem Gesamtnutzen bei –29,02 % (SD ± 47,94) bei einem Minimum von –637,93 %, für B bei –13,42 % (SD ± 13,14) bei einem Minimum von –78,63. Bei den Berechnungen der Verbesserungsquotienten mit positivem Gesamtnutzen unterschieden sich die Verbesserungsquotienten A und B nur geringfügig. Der durchschnittliche APHAB-Score (EC-, BN- und RV-Subskala) betrug 50,70 vor und 29,29 nach einer HGV, der durchschnittliche Gesamtnutzen lag bei 21,41. SCHLUSSFOLGERUNG Der Verbesserungsquotient B vermeidet das in A intrinsisch angelegte Verzerrungspotenzial zugunsten der Fälle, in denen durch die Patienten im APHAB ein negativer subjektiver Nutzen im Rahmen einer HGV angegeben wird. Sinnvoll wäre es, im Rahmen einer weiterentwickelten QSV sowohl den hier neu vorgestellten Verbesserungsquotienten B als auch den kumulierten Gesamtnutzen zu verwenden.Filgotinib is a selective JAK1 (Janus kinase) inhibitor, filed in Japan for the treatment of rheumatoid arthritis. In this paper, we present the data of development and validation of a high-performance liquid chromatography (HPLC) method for the quantitation of filgotinib in mice plasma as per the FDA regulatory guideline. The method involves the extraction of filgotinib along with internal standard (IS, tofacitinib) from mice plasma (100 µL) using ethyl acetate as an extraction solvent. The chromatographic analysis was performed using an isocratic mobile phase comprising 10 mM ammonium acetate (pH 4.5) and acetonitrile (7030, v/v) at a flow-rate of 0.8 mL/min on a Hypersil Gold C18 column. The UV detection wavelength was set at λmax 300 nm. Filgotinib and the IS eluted at 5.56 and 4.28 min, respectively with a total run time of 10 min. The calibration curve was linear over a concentration range of 0.05 to 5.00 μg/mL (r 2+=≥0.992). CX-5461 research buy The intra- and inter-day precision and accuracy results were within the acceptable limits. Results of stability studies indicated that filgotinib was stable on bench-top, in auto-sampler, up to three freeze/thaw cycles and long-term storage at -80°C. The validated HPLC method was successfully applied to a pharmacokinetic study in mice. © Georg Thieme Verlag KG Stuttgart · New York.AIM Trigonelline is a potent phytochemical present in fenugreek, which has strong anti-oxidant and phytoestrogenic activities. This study was carried out to investigate this estrogenic activity as a possible mechanisms involved in preventing the symptoms of osteoporosis in dexamethasone induced osteoporosis in rats. MATERIALS AND METHODS Wistar rats were randomly divided into eight groups, six animals in each group. Osteoporosis was induced using dexamethasone 0.1mg/kg subcutaneously in rats for three times per week for 8 consecutive weeks and treatment with drugs up to 12 weeks as per the treatment schedule described. After 12 weeks, rats were sacrificed; blood samples were collected from each rat and the clear, non hemolysed supernatant sera was used for biochemical examinations. Femurs were used for Bone Mineral Density (BMD), microcomputed tomography (Micro CT), histology and biochemical examinations. RESULTS BMD, bone micro structure, serum calcium, phosphorus level and serum estradiol levels were decreased while serum PTH levels, SAP and acid phosphatase (ACP) were elevated in dexamethasone treated rats as compared to control (p less then 0.01). Dexmethasone treated animals showed loss of marrow at multifocal area, cartilage and trabeculae and thinning of trabeculae (bone resorption), zone of cartilage was poorly seen and fat cells in marrow. Trigonelline showed significant improvement and prevent the progression of osteoporosis by enhancing the BMD, restoring bone physiology. CONCLUSION Our results confirm the estrogenic activity of triogonelline, which is responsible for its effects; still, it needs further evaluation in other animal models to provide a more conclusive view for its therapeutic usefulness in osteoporosis. © Georg Thieme Verlag KG Stuttgart · New York.in English, German Die radikale Zystektomie ist der Goldstandard zur Behandlung des muskelinvasiven Urothelkarzinoms. Insbesondere bei Patienten mit fortgeschrittenen Tumoren spielen multimodale, neoadjuvante oder adjuvante Therapiekonzepte eine zunehmend wichtige Rolle für die optimale Patientenversorgung. Zudem sind bei älteren und komorbideren Patienten, die unfit für eine radikale Zystektomie sind, alternative Therapiekonzepte erforderlich. Dieser Artikel fasst die aktuelle Literatur multimodaler Therapien im neoadjuvanten und adjuvanten Setting zusammen und beleuchtet Alternativen zur radikalen Zystektomie mit kurativem Therapieansatz. Ebenfalls werden erste Erkenntnisse über den Einsatz neuer, vielversprechender Therapieoptionen wie der Immuncheckpoint-Blockade im multimodalen Therapieansatz zusammengefasst.in English, German COVID-19, ausgelöst durch Coronavirus SARS-CoV-2, ist eine neue, sich pandemisch ausbreitenden Infektionserkrankung, welche aktuell weltweit zu einer erheblichen Belastung der Gesundheitssysteme geführt hat. Krankenhausmitarbeiter stellen in Ländern mit hoher Krankheitsaktivität, wie China oder Italien, einen signifikanten Anteil der an COVID-19 Erkrankten und Verstorbenen dar. Bronchoskopische Untersuchungen führen beim untersuchten Patienten zu Hustenreiz und Aerosolbildung und beinhalten daher ein erhöhtes Infektionsrisiko für das Untersuchungsteam und für andere Patienten. In der aktuellen Pandemie sind daher besondere Maßnahmen bei der Durchführung bronchoskopischer Untersuchungen zu beachten, um das Infektionsrisiko zu senken.PURPOSE AND METHODS Phenotype transformation in pituitary adenomas (PA) is a little known and unexpected clinical phenomenon. We describe two illustrative cases and performed a systematic review of cases reported in literature. RESULTS Case 1 A 24-year-old woman underwent surgery because of Cushing's disease. A complete tumor resection and hypercortisolism resolution was achieved. Two years later, tumor recurred but clinical and hormonal hypercortisolism were absent. Case 2 A 77-year-old woman underwent surgery due to acromegaly. A complete tumor resection and GH excess remission was achieved. Four years later, tumor recurred but clinical and hormonal acromegaly was ruled out. Search of literature From 20 patients (including our cases), 75% were female with median age 45 (19) years. Ten patients (50%) had initially functioning PA 8 switched to NFPA (5 ACTH-secreting PA, 2 prolactinomas and 1 acromegaly) and 2 exchanged to acromegaly from TSH-secreting PA and microprolactinoma. One patient developed a pituitary carcinoma from ACTH-secreting PA. Ten patients (50%) initially had NFPA; 9 developed Cushing's disease (4 silent corticotroph adenomas, 4 null cell PA and 1 managed conservatively). One patient with silent somatotroph PA changed to acromegaly. Treatments before transformation were surgery (80%), radiotherapy (40%), pharmacological (40%) and in 2 patients switching happened without any treatment. Median follow-up until transformation was 72 months (range 12-276). CONCLUSION PA can change from functioning to (NF) non-functioning (vice versa) and even exchange their hormonal expression. Clinicians should be aware and a careful lifelong follow-up is mandatory to detect it. © Georg Thieme Verlag KG Stuttgart · New York.BACKGROUND The presence of chronic kidney disease (CKD) influences the type of antiglycaemic therapy and the risk for hypoglycaemia. METHODS In 2006, 2011 and 2016 health insurance data of people with diabetes type 2 were screened for CKD and the presence of severe hypoglycaemia (sHypo). The type of antihyperglycaemic therapy was recorded due to Anatomical Therapeutic Chemical (ATC) codes up to 3 months before suffering sHypo. RESULTS The prevalence of CKD increased from 5.3% in 2006 to 7.3% in 2011 and 11.2% in 2016. Insulin-based therapies were used in 39.0, 39.1, and 37.9% of patients with, but only in 17.7, 17.4, and 18.8% of patients without CKD. Although the proportion of the CKD stages 1, 2 and 5 decreased, CKD stages 3 and 4 increased. The proportion of sHypo in CKD declined from 2006 (3.5%) to 2011 (3.0%) and 2016 (2.2%) but was still more than 10 times higher as compared to type 2 diabetic patients without CKD (0.3/0.2/0.2%) conferring a significantly higher probability of sHypo (OR 9.30, 95%CI 9.07-9.54) in CKD. The probability of sHypo was significantly lower in 2016 than in 2006 both in patients with (OR 0.58; CI 0.55-0.61) and without CKD (OR 0.70; CI 0.68-0.73). CONCLUSION The prevalence of CKD increased from 2006 to 2016. Patients with CKD exhibited a 9-fold increased probability of sHypo, especially in patients treated with insulin plus oral anti-diabetic drugs. However, the rate and risk for sHypo decreased over time, probably as a consequence of new antidiabetic treatment options, better awareness of sHypo, and changed therapy goals. © Georg Thieme Verlag KG Stuttgart · New York.BACKGROUND Combining neuraxial opioids and local anesthetics in acute pain results in improved duration of analgesia and reduced dosages and adverse effects. Although commonly used in intrathecal drug delivery systems (IDDS) for chronic pain, the effectiveness of this admixture has not been examined specifically in relation to patient-controlled intrathecal analgesia (PCIA). METHODS IDDS-implanted chronic noncancer pain patients receiving opioids with bupivacaine (O + B) were randomized to receive either opioids without bupivacaine (O) or O + B in a double-blind manner, at IDDS refills, for one week and then crossed over to the other solution for another week. Primary outcome measures included numeric rating scale (NRS) pain scores before and within 30 minutes after PCIA boluses. Secondary outcome measures included average NRS scores and functional outcome measures. RESULTS Seventeen patients were enrolled, and 16 patients completed the study. There were no differences in NRS scores before and after PCIA boluses between the O and O + B conditions, though pain scores improved significantly (average decrease in NRS scores O 1.
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