Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia.

AIM: To determine the effects of astaxanthin treatment on lipids, cardiovascular disease (CVD) markers, glucose tolerance, insulin action and inflammation in individuals with prediabetes and dyslipidaemia. MATERIALS AND METHODS: Adult participants with dyslipidaemia and prediabetes (n = 34) underwent baseline blood draw, an oral glucose tolerance test and a one-step hyperinsulinaemic-euglycaemic clamp. They were then randomized (n = 22 treated, 12 placebo) to receive astaxanthin 12 mg daily or placebo for 24 weeks. Baseline studies were repeated after 12 and 24 weeks of therapy. RESULTS: After 24 weeks, astaxanthin treatment significantly decreased low-density lipoprotein (-0.33 ± 0.11 mM) and total cholesterol (-0.30 ± 0.14 mM) (both P < .05). Astaxanthin also reduced levels of the CVD risk markers fibrinogen (-473 ± 210 ng/mL), L-selectin (-0.08 ± 0.03 ng/mL) and fetuin-A (-10.3 ± 3.6 ng/mL) (all P < .05). While the effects of astaxanthin treatment did not reach statistical significance, there were trends toward improvements in the primary outcome measure, insulin-stimulated, whole-body glucose disposal (+0.52 ± 0.37 mg/m2 /min, P = .078), as well as fasting [insulin] (-5.6 ± 8.4 pM, P = .097) and HOMA2-IR (-0.31 ± 0.16, P = .060), suggesting improved insulin action. No consistent significant differences from baseline were observed for any of these outcomes in the placebo group. Astaxanthin was safe and well tolerated with no clinically significant adverse events. CONCLUSIONS: Although the primary endpoint did not meet the prespecified significance level, these data suggest that astaxanthin is a safe over-the-counter supplement that improves lipid profiles and markers of CVD risk in individuals with prediabetes and dyslipidaemia.

The impact of a structured one-day seminar on disease-specific knowledge, lifestyle habits and disease impairment in ANCA-associated vasculitis. Results of a randomized, controlled study.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complex, chronic autoimmune disease, and its diagnosis triggers considerable anxiety and uncertainty for those affected. There are currently no valid data describing the impact of disease-specific patient education on the disease knowledge, subjective impairment, and changes in lifestyle habits related to AAV. METHOD: We designed a one-day educational programme to serve AAV patients with information about their disease and its treatment. Patients were randomized into an intervention group and a waiting list control group. Increase in knowledge was measured with a multiple-choice test. The intervention group completed the questionnaire before, directly after, and 3 months after the seminar, while the waiting list control group was additionally tested 3 months before the seminar to rule out non-specific learning. Furthermore, we investigated the burden of the disease and the impact of our intervention on this burden. RESULTS: Compared with the control group, the intervention increased the knowledge (mean ± sd score difference 2.2 ± 1.0, 95% confidence interval 0.1-4.3, p = 0.04). From the patients' point of view, their understanding of the disease had improved and the subjective impairment caused by their rheumatic disease had decreased. There was a tendency to include disease-relevant behaviour, such as nasal care or dietary recommendations, more often in everyday life. CONCLUSION: A one-day seminar is suitable to increase the disease-specific knowledge of patients with AAV in a sustainable manner. In addition, our measure positively affected the disease-relevant behaviour.

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes.

AIMS: To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D). MATERIALS AND METHODS: Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater. RESULTS: During the 7- to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( -27.6 vs. -4.4 mg/dL [-1.5 vs. -0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants. CONCLUSIONS: When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

[Slowly progressive joint destruction in an older man as expression of hydroxyapatite disease. Case report and literature review]. / Langsam progrediente Gelenkzerstörung bei einem älteren Mann als Ausdruck einer Hydroxylapatiterkrankung. Fallbericht und Literaturübersicht.

This article reports the case of a 75-year-old male patient presenting with arthralgia of the large joints that had existed for 10 years. Clinically, bursitis of the right elbow joint was found. Laboratory tests showed elevated inflammatory markers and imaging revealed erosive joint destruction. A surgical bursectomy was performed. Histologically, hydroxyapatite crystals were detected in alizarin red S staining and a crystal arthropathy was diagnosed. The diagnostics are difficult since crystals can only be detected by electron microscopy or special staining methods.

Endoscopic full-thickness resection (EFTR) in the lower gastrointestinal tract.

BACKGROUND: Endoscopic full-thickness resection (EFTR) significantly expands the spectrum of endoscopic colorectal resection methods for lesions that show no lifting sign, submucosal lesions and mucosal carcinomas. The aim of our study was to evaluate the efficacy and safety of EFTR using a commercially available full thickness resection device (FTRD) by assessing the completeness of the full-thickness resection, the technical success, as well as complications in a cohort of patients from three referral centers in Germany. Another aim was to determine which patient subpopulations benefit most in clinical practice. METHODS: This retrospective multicenter study was conducted on consecutive patients who were admitted to three referral centers in Germany between November 2014 and December 2017. The EFTR was conducted according to the standard indications using the FTRD System (OVESCO, Tübingen, Germany). Data were obtained from prospectively maintained institutional databases. RESULTS: There were 70 patients, 42 males and 25 females with a mean age of 79.5 years (range 25-89 years) who had colonoscopy for EFTR. In three patients EFTR was not feasible because the lesions were too large. Of the remaining 67 patients, 52 had recurrent adenomas, 10 had high-grade intraepithelial neoplasia or mucosal carcinoma and five had a subepithelial lesion. Resection was technically successful in 65 patients (97.0%). Histologically complete resection (R0) was achieved in 59/65 patients (90.8%). The R0 resection rate was lower for lesions > 20 mm (86.5%) versus lesions ≤ 20 mm (92.9%). The total complication rate was 14.9%: there was one major complication (perforation of sigmoid colon), while all other complications were minor. CONCLUSIONS: EFTR yields excellent resection rates for benign recurrent adenomas with non-lifting sign, advanced histopathological findings or submucosal lesions when the procedure is performed in experienced hands and for the correct indication. Thus, surgery can be avoided in many cases. For all lesions the risk of R1 resection goes up with the size of the lesion and careful patient selection is mandatory.

[Successful pembrolizumab therapy in metastasized adenosquamous carcinoma of the colon]. / Erfolgreiche Pembrolizumab-Therapie bei metastasiertem adenosquamösem Karzinom des Kolons.

Adenosquamous carcinoma (ASqC) is an exceedingly rare subtype of colorectal cancer without any known special guidelines for treatment. The biological behaviour and molecular background are widely unknown, although a few case studies report a worse prognosis compared to ordinary colorectal adenocarcinoma. We herein report for the first time the successful immune checkpoint inhibitor therapy in a 40-year-old patient suffering from metastasized right-sided colonic ASqC with unique molecular features, after having previously progressed under standard chemotherapy.

[A 34-year-old patient with retropharyngeal tendinitis]. / Ein 34-jähriger Patient mit retropharyngealer Tendinitis.

This article reports the case of a 34-year-old male patient presenting with neck pain, massive pressure pain of the neck muscles and limited cervical rotational mobility. Laboratory tests showed elevated levels for markers of inflammation. Computed tomography (CT) and magnetic resonance imaging (MRI) detected a retropharyngeal tendinitis of the longus cervicis muscle. This rare clinical entity is probably responsible for a high number of unreported cases. A CT scan, which can identify prevertebral edema and light calcification inferior to the ventral aspect of the second cervical vertebra, was previously the gold standard. Meanwhile, MRI scans now show a higher sensitivity in the detection of prevertebral edema. The first line treatment is the administration of non-steroidal anti-inflammatory drugs (NSAIDs).

Mapping the electric field distribution of tightly focused cylindrical vector beams with gold nanorings.

In this paper gold nanorings (NRs) are applied as particularly well-suited sensing elements for mapping the radially symmetric electric fields in the high numerical aperture focus of cylindrical vector beams. The optical properties of gold nanorings are analyzed by a combination of extinction and single particle dark field spectroscopy as well as confocal photoluminescence (PL) imaging. The results are compared to numerical calculations. The in-plane components in the focus of the cylindrical vector beams are estimated through the PL intensity distributions of the NRs. The optimum overlap between the structure and excitation is visualized by a narrow centre spot in the far-field PL scan.

Fluoride-fiber-based side-pump coupler for high-power fiber lasers at 2.8 µm.

A side-pump coupler made of fluoride fibers was fabricated and tested. The tested device had a coupling efficiency of 83% and was driven with an incident pump power of up to 83.5 W, demonstrating high-power operation. Stable laser output of 15 W at a wavelength of around 2.8 µm was achieved over 1 h when using an erbium-doped double-clad fiber as the active medium. To the best of our knowledge, this is the first time a fluoride-glass-fiber-based side-pump coupler has been developed. A test with two devices demonstrated further power scalability.

Transfer, loss and physical processing of water in hit-and-run collisions of planetary embryos.

Collisions between large, similar-sized bodies are believed to shape the final characteristics and composition of terrestrial planets. Their inventories of volatiles such as water are either delivered or at least significantly modified by such events. Besides the transition from accretion to erosion with increasing impact velocity, similar-sized collisions can also result in hit-and-run outcomes for sufficiently oblique impact angles and large enough projectile-to-target mass ratios. We study volatile transfer and loss focusing on hit-and-run encounters by means of smooth particle hydrodynamics simulations, including all main parameters: impact velocity, impact angle, mass ratio and also the total colliding mass. We find a broad range of overall water losses, up to 75% in the most energetic hit-and-run events, and confirm the much more severe consequences for the smaller body also for stripping of volatile layers. Transfer of water between projectile and target inventories is found to be mostly rather inefficient, and final water contents are dominated by pre-collision inventories reduced by impact losses, for similar pre-collision water mass fractions. Comparison with our numerical results shows that current collision outcome models are not accurate enough to reliably predict these composition changes in hit-and-run events. To also account for non-mechanical losses, we estimate the amount of collisionally vaporized water over a broad range of masses and find that these contributions are particularly important in collisions of ∼  Mars-sized bodies, with sufficiently high impact energies, but still relatively low gravity. Our results clearly indicate that the cumulative effect of several (hit-and-run) collisions can efficiently strip protoplanets of their volatile layers, especially the smaller body, as it might be common, e.g., for Earth-mass planets in systems with Super-Earths. An accurate model for stripping of volatiles that can be included in future planet formation simulations has to account for the peculiarities of hit-and-run events and track compositional changes in both large post-collision fragments.

Combination SGLT2 Inhibitor and Glucagon Receptor Antagonist Therapy in Type 1 Diabetes: A Randomized Clinical Trial.

OBJECTIVE: To examine the effects of insulin-adjunctive therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor and a glucagon receptor antagonist (GRA) on glycemia, insulin use, and ketogenesis during insulinopenia in type 1 diabetes. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, crossover trial we assessed the effects of adjunctive SGLT2 inhibitor therapy (dapagliflozin 10 mg daily) alone and in combination with the GRA volagidemab (70 mg weekly) in 12 adults with type 1 diabetes. Continuous glucose monitoring, insulin dosing, and insulin withdrawal tests (IWT) for measurement of glucose and ketogenesis during insulinopenia were completed during insulin-only (Baseline), SGLT2 inhibitor, and combination (SGLT2 inhibitor + GRA) therapy periods. RESULTS: Average glucose and percent time with glucose in range (70-180 mg/dL) improved with combination therapy versus Baseline and SGLT2 inhibitor (131 vs. 150 and 138 mg/dL [P < 0.001 and P = 0.01] and 86% vs. 70% and 78% [P < 0.001 and P = 0.03], respectively) without increased hypoglycemia. Total daily insulin use decreased with combination therapy versus Baseline and SGLT2 inhibitor (0.41 vs. 0.56 and 0.52 units/kg/day [P < 0.001 and P = 0.002]). Peak ß-hydroxybutyrate levels during IWT were lower with combination therapy than with SGLT2 inhibitor (2.0 vs. 2.4 mmol/L; P = 0.048) and similar to levels reached during the Baseline testing period (2.1 mmol/L). Participants reported enhanced treatment acceptability and satisfaction with combination therapy. CONCLUSIONS: Glucagon antagonism enhances the therapeutic effects of SGLT2 inhibition in type 1 diabetes. Combination therapy improves glycemic control, reduces insulin dosing, and suggests a strategy to unlock the benefits of SGLT2 inhibitors while mitigating the risk of diabetic ketoacidosis.

Proxy assessment of patients before and after radiotherapy for brain metastases. Results of a prospective study using the DEGRO brain module.

PURPOSE: Proxies of patients with poor performance status could give useful information about the patients' quality of life (QoL). We applied a newly developed questionnaire in a prospective QoL study of patients undergoing radiotherapy for brain metastases in order to make the first move to validate this instrument, and we compared the results with scores obtained using validated patient-completed instruments. MATERIALS AND METHODS: From January 2007 to June 2010, 166 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module BN20 were used to assess QoL in patients at the start of treatment and 3 months later. At the same time points, 141 of their proxies estimated the QoL with the new DEGRO brain module (DBM), a ten-item questionnaire rating the general condition as well as functions and impairment by symptoms in areas relevant to patients with brain metastases. RESULTS: At 3 months, 85 of 141 patients (60%) with initial response by a proxy were alive. Sixty-seven of these patients (79% of 3-month survivors) and 65 proxies completed the second set of questionnaires. After 3 months, QoL significantly deteriorated in all items of proxy-assessed QoL except headache. Correlations between self-assessed and proxy-assessed QoL were high in single items such as nausea, headache, and fatigue. CONCLUSIONS: The high correlation between self-assessment and proxy ratings as well as a similar change over time for both approaches suggest that in patients with brain metastases, proxy assessment using the DBM questionnaire can be an alternative approach to obtaining QoL data when patients are unable to complete questionnaires themselves. Our self-constructed and first applied DBM is the only highly specific instrument for patients with brain metastases, but further tests are needed for its final validation.

Prediction of on-road driving ability after traumatic brain injury and stroke.

BACKGROUND AND PURPOSE: The aim of the study was to examine the predictive value of widely used standardized neuropsychological tests in a clinical setting for on-road driving performance in patients with cerebral stroke or traumatic brain injury (TBI), and to provide cut-off values for neuropsychological test results under which driving should not be recommended. METHODS: Data from 78 patients who had undergone comprehensive driving assessment after stroke or TBI were retrospectively included in the analysis. Patients underwent medical examination, neuropsychological testing and on-road assessment. Medical data, demographic variables and neuropsychological performance were used as predictors in a stepwise logistic regression analysis with pass/fail after the on-road test as the dependent variable. Receiver operating characteristic curve analysis was employed to select cut-off values for the tests that were significant predictors for on-road performance. RESULTS: Forty-three patients passed and 35 failed the on-road driving task. Logistic regression analysis revealed three significant neuropsychological tests (CalCap simple reaction time, Trail Making Test A, Grooved Pegboard) as predictors for on-road performance explaining 46% of the variance with an overall classification accuracy of 82.1%. Receiver operating characteristic curve analysis showed the following cut-off values: CalCap, 395 ms; Trail Making Test A, 46 s; Grooved Pegboard, 97.5 s. CONCLUSION: The results suggest that driving ability after brain damage and cerebral disease with no severe neurological deficits can be measured with a few distinctive neuropsychological tests together with medical examination and on-road assessment. Cut-off scores are a useful supplement to normative data/scaled scores.

[Anxiety and depression in cancer patients during the course of radiotherapy treatment]. / Angst und Depressivität bei Tumorpatienten im Verlauf der radioonkologischen Behandlung.

BACKGROUND: Undergoing radiotherapy is often associated with severe impairment of quality of life in cancer patients. Especially psychosocial aspects like anxiety and depression play a major role. The aim of this study was to closely analyze anxiety and depression during the course of radiotherapy treatment. METHODS: A total of 60 patients, who received radiotherapy because of a tumor disease between June 2005 and April 2006, were included in the prospective study; 57 (95%) patients were primarily treated with radiotherapy. In 72% of the cases the intention to treat was curable, in 18% palliative. Anxiety and depression (HADS-D) were assessed at three points in time: before (A) and after (B) radiotherapy treatment (RT), and 6 weeks after finishing RT at the follow-up appointment (C). RESULTS: Before therapy (A), 41% of the treated patients showed positive or marginally positive symptoms of anxiety and 33% symptoms of depression. The symptoms of anxiety significantly decreased during the course of therapy. The proportion of patients with a positive score of anxiety dropped from 16% at the beginning of RT (A) to 9% after the RT (B; p = 0.04). In addition, there was an increase in the number of patients who scored negatively with regard to anxiety from 59% (A) to 72% (B; p = 0.04). With regard to the median score of anxiety, no statistically significant change (p > 0.05) was observed during therapy, while for depression, the number of positively tested patients also decreased significantly during the course of therapy from the beginning of RT (A, 14%) to the first follow-up appointment (C, 9%; p = 0.02). Furthermore, the number of negatively tested patients rose by 8% (p = 0.02). During the whole course of the study, the median score of depression decreased from 6 (A) to 5 points (C; p = 0.01). CONCLUSION: More than one third of the treated patients suffered from positive or marginally positive symptoms of anxiety and depression. This present study showed a decrease of anxiety and depression symptoms during the course of radiotherapy.

Patient satisfaction during radiation therapy. Correlates and patient suggestions.

BACKGROUND: Assessing patient satisfaction might help to detect so far unknown patient needs and could contribute to quality assurance within the health care system. We evaluated patient satisfaction and its correlates in a consecutive sample of patients undergoing external beam radiation therapy. PATIENTS AND METHODS: Patient satisfaction was evaluated within a prospective study with two validated instruments (FPZ, ZUF-8) during the first week of radiation therapy in two university-based radiation oncology departments. RESULTS: A total of 273 patients could be analyzed. Most patients were irradiated for breast or urogenital cancer. Overall patient satisfaction was high (94.9-98.8%). The most important items for patient satisfaction included the following: "skills of physicians" followed by "physician contact with patients," "care," and "information" (Tab. 2). Neither center nor disease entity correlated with global patient satisfaction. Of the patients, 46% reported that they would have preferred additional information prior to the onset of radiotherapy. Patients who sought additional information reported a lower global patient satisfaction (p < 0.001). In multiple linear regression analysis, the need for more information, male gender, and a higher level of education were significant predictors for lower global patient satisfaction (Tab. 6). CONCLUSION: During the first week of radiation therapy, patients rate patient-physician interaction and communication on treatment and disease as important factors for their satisfaction. Supplying additional information to subsets of patients prior to starting radiotherapy might help to further improve satisfaction.

SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants With Type 1 Diabetes.

Individuals with type 1 diabetes have an impaired glucagon counterregulatory response to hypoglycemia. Sodium-glucose cotransporter (SGLT) inhibitors increase glucagon concentrations. We evaluated whether SGLT inhibition restores the glucagon counterregulatory hormone response to hypoglycemia. Adults with type 1 diabetes (n = 22) were treated with the SGLT2 inhibitor dapagliflozin (5 mg daily) or placebo for 4 weeks in a randomized, double-blind, crossover study. After each treatment phase, participants underwent a hyperinsulinemic-hypoglycemic clamp. Basal glucagon concentrations were 32% higher following dapagliflozin versus placebo, with a median within-participant difference of 2.75 pg/mL (95% CI 1.38-12.6). However, increased basal glucagon levels did not correlate with decreased rates of hypoglycemia and thus do not appear to be protective in avoiding hypoglycemia. During hypoglycemic clamp, SGLT2 inhibition did not change counterregulatory hormone concentrations, time to recovery from hypoglycemia, hypoglycemia symptoms, or cognitive function. Thus, despite raising basal glucagon concentrations, SGLT inhibitor treatment did not restore the impaired glucagon response to hypoglycemia. We propose that clinical reduction in hypoglycemia associated with these agents is a result of changes in diabetes care (e.g., lower insulin doses or improved glycemic variability) as opposed to a direct, physiologic effect of these medications on α-cell function.

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

Photoinduced reconfiguration cycle in a molecular adsorbate layer studied by femtosecond inner-shell photoelectron spectroscopy.

A time-resolved study of core-level chemical shifts in a monolayer of aromatic molecules reveals complex photoinduced reaction dynamics. The combination of electron spectroscopy for chemical analysis and ultrashort pulse excitation in the extreme ultraviolet allows performing time-correlated 4d-core-level spectroscopy of iodine atoms that probe the local chemical environment in the adsorbate molecule. The selectivity of the method unveils metastable molecular configurations that appear about 50 ps after the excitation and are efficiently quenched back to the ground state.