Changes in incidence of severe hypoglycaemia in people with type 2 diabetes from 2006 to 2016: analysis based on health insurance data in Germany considering the anti-hyperglycaemic medication.

AIM: To investigate the incidence of severe hypoglycaemia over the past 10 years, taking into account changes in anti-hyperglycaemic therapy. METHODS: This retrospective population-based study used German health insurance data. All adults diagnosed with documented type 2 diabetes (extrapolated to the German population: 6.6 million in 2006; 7.9 million in 2011; 8.86 million in 2016) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by Anatomical Therapeutic Chemical (ATC) code. RESULTS: The event rate for severe hypoglycaemia was 460 per 100 000 people in 2006, 490 per 100 000 in 2011 and 360 per 100 000 in 2016. The proportion of people with severe hypoglycaemia receiving sulfonylureas, as well as receiving combination therapy of metformin and sulfonylureas decreased from 2006 to 2016 (23.6% vs. 6.2%) Among those with severe hypoglycaemia in 2006, there were no prescriptions for dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose co-transporter 2 (SGLT2) agonists. The proportions of people with severe hypoglycaemia receiving DPP-4 inhibitors, GLP-1 receptor agonists or SGLT2 agonists in 2011 and 2016 were low. The proportion of people receiving human insulin also decreased (from 11.3% in 2006 to 10.3% in 2011 and 4.3% in 2016); the proportion of people receiving insulin analogues increased from 5.4% in 2006 to 11.5% in 2016. Therapy with mixed insulins was used by 19.7% of people with severe hypoglycaemia in 2006, by 14.0% in 2011 and by 7.3% in 2016. People undergoing therapy with insulin analogues have the highest risk of severe hypoglycaemia adjusted by age, gender, nephropathy diagnosis and year of survey [odds ratio (OR) 14.4, 95% confidence interval (95% CI) 13.5-15.5]. CONCLUSION: The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, and decreased in 2016.

Distinct proteasome subpopulations in the alveolar space of patients with the acute respiratory distress syndrome.

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL ± 1116 versus 59 ± 25; P < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation.

Characterization of quaternary ammonium oligomers by paired-ion reversed-phase liquid chromatography-mass spectrometry.

The separation of novel permanently charged oligomers was studied using paired-ion reversed-phase liquid chromatography. The polyionene studied is less than 5 kDa in size, but contains three oligomer series with different end-group chemistries. The complexity of this polyionene makes development of a single-dimension separation quite challenging. Separation under critical conditions was employed to fractionate the end-group conformations and then the chain length of the oligomers in each series was confirmed by LC-MS. The oligomers were then used to optimize a single-dimension HPLC separation. Precise modulation of the hydrophobicity of the ion-pair reagent and the stationary-phase chemistry yielded very high resolution one-dimensional separations.

[In vitro study of endothelial tolerance of 10 culture media with special reference to the pump and barrier function]. / In-vitro-Untersuchung der Endothelverträglichkeit von 10 Kulturmedien unter besonderer Berücksichtigung der Pump- und Barrierefunktion.

We investigated ten commercially available tissue culture media in a series of perfusion experiments. Porcine cornea were perfused in groups of 10-15 with the media M 199 Earle, MEM Earle, MEM Hank, DMEM, RPMI 1640, Ham's F-12, BM-86 Wissler. Perfusions were done with and without the addition of 2% fetal calf serum. As a control, BSS PLUS (R) was used. We compared the change in corneal thickness in a 6-h perfusion interval. The corneal endothelium was present after all perfusion experiments. Evaluation of the changes in corneal thickness showed that culture media rich in bicarbonate support the endothelial pumping function. The presence of fetal calf serum had no influence on corneal thickness. The absence of glutathione in the culture media did not result in increased corneal thickness. Medium 199 with Earle salt, BSS Plus, DMEM, RPMI 1640 and Ham's F-12 gave the best results and may be considered possible intraocular irrigation solutions.

[Autoimmune haemolytic anaemia, thrombocytopenia and thyroiditis: an immunopathological triad (author's transl)]. / Autoimmune hämolytische Anämie, Thrombozytopenie und Thyreoiditis: eine immunpathologische Trias.

A 37-year-old woman developed acquired haemolytic anaemia and thrombocytopenic purpura. At the same time there were signs of hypothyroidism. Incomplete heat antibodies (direct Coombs test) were demonstrated as cause of the haemolytic changes, while high-titre thyroglobulin and microsomal thyroid antibodies as cause of the immunothyroiditis explained the hypothyroidism. Although serological demonstration of platelet antibodies did not succeed, the clinical and haematological findings suggested immunothrombocytopenia. Antibodies against smooth muscle produced no clinical symptoms. The activity of the incomplete heat autoantibodies was diminished as result of immunosuppressive treatment and haemolytic signs regressed. Platelet count rose and the haemorrhagic diathesis disappeared. Thyroid antibody titre rose at first but then markedly decreased. There was no demonstrable effect on the hypothyroidism so that it was necessary to administer thyroid hormones. This is the first published case of such immunopathological triad resulting from immunothyroiditis.

[Diagnosis and therapy of lymphoid tumors of the orbits]. / Diagnostik und Therapie lymphoider Tumoren der Orbita.

For the evaluation of neoplastic orbital lesions an interdisciplinary concept is crucial and includes modern imaging techniques as well as rhinosurgical approaches to the orbit. During a 14-year period 6 primary malignant orbital lymphomas and 9 cases of orbital pseudotumors were managed at our department. In most of the cases an exophthalmus with painful swelling of the eyelids, diplopia and a loss of vision were the clinical symptoms. Imaging using CT or MRI revealed homogeneous tissue formations that could not be clearly demarcated from adjacent orbital structures. By a rhinosurgical approach a biopsy was performed of each lesion without surgical complications. Following diagnosis the localized malignant lymphomas of the orbit were irradiated. In one patient systemic spread of tumor required multi-drug chemotherapy. Two patients died as the result of the sequleae of disseminated plasmocytomas. Patients with orbital pseudotumors were treated with systemic steroids. Two patients were also irradiated. No malignant transformation of any orbital pseudotumor was observed in this series. Our experiences show that careful histological evaluation of lymphoid orbital masses is necessary for correct diagnosis, especially since this has great impact on treatment and prognosis. Depending on the localization of a lesion medial orbitotomy by a rhinosurgical approach has proven to be a safe method for performing a biopsy or extirpating tumor.