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ZusammenfassungDie Messung von spezifischen Autoantikörpern gegen beta-Zellproteine (beta-AAK) hat in den letzten Jahren das diagnostische Repertoire in der Diabetologie erweitert. Das Vorliegen von beta-AAK kann als erstes Stadium in der Entwicklung eines Typ-1-Diabetes mellitus (DM) gewertet werden, ohne dass Symptome bzw. metabolische Veränderungen vorliegen. Da sich diese oft Jahre vor der klinischen Manifestation in Personen mit hohem Erkrankungsrisiko nachweisen lassen, stellen sie wichtige prädiktive und frühdiagnostische Marker dar. Weiterhin kann die Bestimmung von beta-AAK zur Unterscheidung von Patienten mit einem Typ-1-DM auf der einen und Typ-2-DM und Maturity-Onset Diabetes of the Young (MODY) auf der anderen Seite indiziert sein. Auch für die Differenzialdiagnostik von Patienten mit Insulinmangel aufgrund einer autoimmunen Betazelldestruktion und von Patienten mit klinisch sehr ähnlichem „severe-insulin-deficient“-Diabetes, die aber beide eine unterschiedliche Prognose haben, ist die Antikörperdiagnostik zielführend. Die Abschätzung des Risikos für die Entwicklung eines Typ-1-DM bei Patienten, die an autoimmunen Endokrinopathien leiden, stellt einen weiteren Einsatzbereich für beta-AAK dar.Analytisch sind die beta-AAK mit recht unterschiedlichen Methoden messbar; häufig aber weichen die erhaltenen Messergebnisse bei verschiedenen Testmethoden beträchtlich voneinander ab. Es müssen daher eigene Cut-off Werte vom beauftragten Labor definiert werden, um die erhaltenen Ergebnisse klinisch interpretieren zu können. Zur besseren Vergleichbarkeit der Messergebnisse gibt es derzeit international abgestimmte Harmonisierungsbestrebungen. Für teilnehmende Laboratorien angebotene Ringversuche für die Bestimmungen der Autoantikörper gegen Insulin (IAA), Insulinoma-Antigen 2 (IA-2), Zink Transporter-8 (ZnT8) und Glutamatdecarboxylase (GAD65) können die analytische Qualität ebenfalls verbessern.

CA extern The relationship between SARS-CoV-2 quantitative viral load and risk of disease progression, morbidity such as long-COVID or mortality in immunosuppressed, remains largely undefined in COVID-19 patients. Critically ill immunosuppressed patients potentially benefit from remdesivir treatment because of the prolonged course of their infection. Four critically ill immunocompromised patients and the impact of remdesivir on viral dynamics in lower respiratory samples were studied. Bronchoalveolar lavage (BAL) samples were assessed to measure SARS-CoV-2 quantitative viral load using real-time PCR. Corresponding plasma levels of remdesivir and its metabolite GS-441524 were determined. Mean virus load of 39.74 x 10(7) geq/ml (+/- 33.25 x 10(7) geq/ml) on day 1 dropped significantly (p

Background Amino acid co-infusion for renal protection in endoradiotherapy (ERT) applied as prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) or peptide receptor radionuclide therapy (PRRT) has been shown to cause severe hyperkalemia. The pathophysiology behind the rapid development of hyperkalemia is not well understood. We hypothesized that the hyperkalemia should be associated with metabolic acidosis. Results Twenty-two patients underwent ERT. Prior to the first cycle, excretory kidney function was assessed by mercapto-acetyltriglycine (MAG-3) renal scintigraphy, serum biochemistry, and calculated glomerular filtration rate (eGFR). All patients received co-infusion of the cationic amino acids L-arginine and L-lysine for nephroprotection. Clinical symptoms, electrolytes, and acid-base status were evaluated at baseline and after 4 h. No patient developed any clinically relevant side effects. At baseline, acid base status and electrolytes were normal in all patients. Excretory kidney function was normal or only mildly impaired in all except two patients with stage 3 renal insufficiency. All patients developed hyperkalemia. Base excess and HCO3− were significantly lower after 4 h. In parallel, mean pH dropped from 7.36 to 7.29. There was a weak association between calculated (r = − 0.21) as well as MAG-3-derived GFR (r = − 0.32) and the rise in potassium after 4 h. Conclusion Amino acid co-infusion during ERT leads to severe metabolic acidosis which induces hyperkalemia by potassium hydrogen exchange. This novel finding implies that commercially available bicarbonate solutions might be an easy therapeutic option to correct metabolic acidosis rapidly. Electronic supplementary material The online version of this article (10.1186/s13550-018-0370-z) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text, The influence of perioperative transfusion (PT) on outcome following surgery for gastric cancer (GC) remains controversial, with randomized trials lacking and observational series confounded by patient risk factors. This analysis determines the association between reception of leukocyte-depleted blood products and post-operative survival for GC. Data from 610 patients who underwent curative surgery for GC in a German tertiary care clinic from 2001 to 2013 were included. Kaplan–Meier survival curves and Cox proportional hazards regression were applied to determine the association of PT and clinical and patient risk factors for overall and relapse-free survival. Propensity score analysis was performed to adjust for observational biases in reception of PT. Higher Union International Contre le Cancer/American Joint Committee on Cancer (UICC/AJCC)-stages (P

Aim This 12-month study was conducted to evaluate the skeletal effects of two monophasic oral contraceptives containing 20 μg of ethinylestradiol and 100 μg of levonorgestrel (LEVO) or 150 μg of desogestrel (DESO). Methods Fifty-two women (18–24 years) were randomized into the DESO group or the LEVO group; 36 women served as controls. The areal bone mineral density (aBMD) of the femoral neck and the lumbar spine was evaluated by DXA, and parameters of bone geometry and volumetric bone mineral density (vBMD) were assessed by peripheral quantitative computed tomography at the distal radius and the tibia. Results The LEVO group did not lose vertebral aBMD, whereas women in the DESO group lost 1.5%. At the distal radius and the tibia (shank level, 14%), LEVO induced an increase in total cross-sectional area, indicating increased periosteal bone formation. Radial trabecular vBMD declined by 1.4±1.8% in the DESO group, while it remained unchanged in the LEVO group. Conclusion Our study suggests that the skeletal effects of OC preparations may be influenced by progestogenic components in young women.

We describe herein PROTIS, a software package that allows for the combination of urine biomarkers (proteins, small molecules, cells) to provide accurate diagnostic information on renal disease states. Such an approach exemplifies the advantage conferred by using multiple markers, and can be generalized for identification of biomarker signatures to separate distinct sample groups.

Insulin is a hormone crucial to metabolism and an essential growth factor for normal and neoplastic tissues. We have now determined insulin in extracts of 23 primary breast cancer specimens and of non-neoplastic breast tissues by a chemiluminescent immunoassay. Remarkably, insulin was measured only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland were each insulin-negative. We also performed immunohistochemistry for insulin-degrading enzyme (IDE), a cytoplasmic zinc metalloprotease belonging to the inverzincin family and participating in insulin cleavage. IDE was detected in most insulin-positive grade 3 carcinomas, indicating that it might be dysfunctional in these anaplastic tumors. IDE was equally present in the insulin-negative grade 2 carcinomas. Moreover, five grade 3 carcinomas and one grade 2 carcinoma displayed a loss of heterozygosity in the 10q chromosomal region harboring the IDE gene, but, despite these alterations, IDE was detected immunohistochemically, indicating a retention of the second allele. Compared to the expression of IDE in 92% of the tumors examined, only 57% of 21 normal breast specimens stained positively for IDE. In contrast to this increase in IDE-positive epithelial cells in breast cancer vs. normal breast, additional immunohistochemical analysis of 17 node-positive breast carcinomas and corresponding tumor-bearing lymph nodes showed that IDE expression decreases from primary tumor to lymph node metastasis. Altogether, this study represents the first demonstration of IDE in normal and neoplastic human mammary tissues. Our present report should also provide an experimental starting point towards exploring a potential role of IDE in the control of tumor progression.

We have proposed boron-containing ether lipids as boron carriers for BNCT; because these are expected to accumulate selectively in tumors.1 These properties depend most probably on the absence of an ether lipid-cleaving enzyme, namely alkyl glycerol monooxidase (AGMO) in a variety of tumors.2 Encouraged by these results we have synthesized the carborane substituted derivative 1 and analogs.1

Objective To describe patients who developed allergic reactions (ie, erythema on their face and body, itching, flushing, drop in blood pressure, respiratory distress, and cold sweats) immediately after intravenous injection of prednisolone hemisuccinate (Solu-Decortin H, E Merck, Darmstadt, Germany). Setting Academic medical center. Results Three of 4 patients had a positive reaction to an intracutaneous test with prednisolone hemisuccinate (Solu-Decortin H) but no reaction to the additive sodium succinate. The results of the prick test were negative for all patients. Although no specific IgE antibodies were detected in the serum of these patients, allergic reaction was noted in 3 cases, since standardized techniques to detect antibodies in the serum for hydrocortisone acetate (ie, prednisolone) are lacking. One female patient had a cross-reaction to prednisolone and dexamethasone (Fortecortin, E Merck, Darmstadt, Germany). A renewed application of prednisolone hemisuccinate was well tolerated by all patients when histamine1and histamine2receptors were blocked with the use of cimetidine hydrochloride, 200 mg twice per day (1-0-1 ampules, Tagamet, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa) and dimethindene maleate, 4 mg twice per day (1-0-1 ampules, Fenistil, Novartis, Munich, Germany); calcium was given for membrane stabilization. Conclusions Allergic reactions to glucocorticoid therapy are only occasionally mentioned in the literature. These reactions appear more often when glucocorticoids are applied topically and may lead to dangerous complications in patients if administered systemically. Therefore, when allergic reactions result from glucocorticoid therapy, (immediate-type reactions should be suspect), consider corticosteroid allergy as a differential diagnosis.