Structural evolution in Au- and Pd-based metallic glass forming liquids and the case for improved molecular dynamics force fields.

The results of a combined experimental and computational investigation of the structural evolution of Au81Si19, Pd82Si18, and Pd77Cu6Si17 metallic glass forming liquids are presented. Electrostatically levitated metallic liquids are prepared, and synchrotron x-ray scattering studies are combined with embedded atom method molecular dynamics simulations to probe the distribution of relevant structural units. Metal-metalloid based metallic glass forming systems are an extremely important class of materials with varied glass forming ability and mechanical processibility. High quality experimental x-ray scattering data are in poor agreement with the data from the molecular dynamics simulations, demonstrating the need for improved interatomic potentials. The first peak in the x-ray static structure factor in Pd77Cu6Si17 displays evidence for a Curie-Weiss type behavior but also a peak in the effective Curie temperature. A proposed order parameter distinguishing glass forming ability, 1/ST,q1-1, shows a peak in the effective Curie temperature near a crossover temperature established by the behavior of the viscosity, TA.

Health care utilization and excess costs after pelvic fractures among older people in Germany.

Our study demonstrates a strong increase in utilization of inpatient health care and clear excess costs in older people in the first year after pelvic fracture, the latter even after adjustment for several confounders. Excess costs were particularly high in the first few months and mainly attributable to inpatient treatment. INTRODUCTION: We aimed to estimate health care utilization and excess costs in patients aged minimum 60 years up to 1 year after pelvic fracture compared to a population without pelvic fracture. METHODS: In this retrospective population-based observational study, we used routine data from a large statutory health insurance (SHI) in Germany. Patients with a first pelvic fracture between 2008 and 2010 (n=5685, 82% female, mean age 80±9 years) were frequency matched with controls (n=193,159) by sex, age at index date, and index month. We estimated health care utilization and mean total direct costs (SHI perspective) with 95% confidence intervals (CIs) using BCA bootstrap procedures for 52 weeks before and after the index date. We calculated cost ratios (CRs) in 4-week intervals after the index date by fitting mixed two-part models including adjustment for possible confounders and repeated measurement. All analyses were further stratified for men/women, in-/outpatient-treated, and major/minor pelvic fractures. RESULTS: Health care utilization and mean costs in the year after the index date were higher for cases than for controls, with inpatient treatment being particularly pronounced. CRs (95% CIs) decreased from 10.7 (10.2-11.1) within the first 4 weeks to 1.3 (1.2-1.4) within week 49-52. Excess costs were higher for inpatient than for outpatient-treated persons (CRs of 13.4 (12.9-13.9) and 2.3 (2.0-2.6) in week 1-4). In the first few months, high excess costs were detected for both persons with major and minor pelvic fracture. CONCLUSION: Pelvic fractures come along with high excess costs and should be considered when planning and allocating health care resources.

Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Current controversies in trichology: a European expert consensus statement.

INTRODUCTION: Hair disorders are one of the most common conditions within dermatology practice but, although new diagnostic tools and therapeutic options have arisen, the management of these patients still represents a major clinical challenge. OBJECTIVE: This study aimed at gathering information and achieving consensus on relevant recommendations on the latest advances in alopecia, trichoscopy and hair dermocosmetics. METHODS: Experts of the steering committee consulted the available evidence on trichology-related areas from the past 5 years and formulated recommendations based on the evidence and their experience. A modified two-round Delphi procedure was performed among 45 European dermatologists experts in trichology to consult their degree of agreement on twenty recommendations, using a 4-point Likert scale. Consensus was defined as >80% of participants scoring either 1 (totally agree) or 2 (agree). RESULTS: In the first round of the Delphi questionnaire, 75% of the recommendations reached consensus. Those that were not agreed upon were reformulated by the steering committee and voted again after an online meeting, where consensus was achieved in all recommendations. CONCLUSIONS: All recommendations reached consensus after the two-round Delphi questionnaire and may be useful in clinical practice for dermatologists. The participants agreed that besides this consensus, further clinical studies are needed to assess the benefits of the emerging tools and treatments and to clarify the controversies that still exist in the field, aiming at improving patients' quality of life.

Frontal fibrosing alopecia: demographic and clinical characteristics of 490 cases.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia mostly affecting the frontotemporal hairline. Its aetiology and associated factors remain unclear. OBJECTIVE AND METHODS: An observational, cross-sectional and descriptive study was conducted in France and Germany to identify demographic and health characteristics associated with the severity of FFA. RESULTS: Of 490 included patients, 95% were female, of which 84% were postmenopausal. Age at onset of FFA symptoms ranged between 15 and 89 years, but diagnosis was frequently delayed up to 24 years. Lichen Planopilaris Activity Index scores were low (median 1.8, IQR 1.0 to 3.5). Thyroid function disorders were reported in 13% of men and 35% of women. Abnormal blood lipid levels were found in 42% of tested men and 47% of women. In the bivariate analyses, LPPAI scores were negatively correlated with abnormal testosterone (rs  = -0.775) and oestrogen values (rs  = -0.664), regular use of face cleaning products (rs  = -0.465), hair colourants (rs  = -0.679) and hairspray (rs  = -0.500). CONCLUSIONS: The most common comorbidity was thyroid disease, with proportions higher than in the European population, possibly reflecting a role of thyroid hormones in FFA pathogenesis. The association of abnormal testosterone and oestrogen values with lesser disease activity needs to be explored in further studies. Our correlation analyses do not support a role of leave-on cosmetic products in the pathophysiology of FFA.

Near-real-time pulmonary shunt and dead space measurement with micropore membrane inlet mass spectrometry in pigs with induced pulmonary embolism or acute lung failure.

The multiple inert gas elimination technique (MIGET) using gas chromatography (GC) is an established but time-consuming method of determining ventilation/perfusion (VA/Q) distributions. MIGET-when performed using Micropore Membrane Inlet Mass Spectrometry (MMIMS)-has been proven to correlate well with GC-MIGET and reduces analysis time substantially. We aimed at comparing shunt fractions and dead space derived from MMIMS-MIGET with Riley shunt and Bohr dead space, respectively. Thirty anesthetized pigs were randomly assigned to lavage or pulmonary embolism groups. Inert gas infusion (saline mixture of SF6, krypton, desflurane, enflurane, diethyl ether, acetone) was maintained, and after induction of lung damage, blood and breath samples were taken at 15-min intervals over 4 h. The samples were injected into the MMIMS, and resultant retention and excretion data were translated to VA/Q distributions. We compared MMIMS-derived shunt (MM-S) to Riley shunt, and MMIMS-derived dead space (MM-VD) to Bohr dead space in 349 data pairs. MM-S was on average lower than Riley shunt (- 0.05 ± 0.10), with lower and upper limits of agreement of - 0.15 and 0.04, respectively. MM-VD was on average lower than Bohr dead space (- 0.09 ± 0.14), with lower and upper limits of agreement of - 0.24 and 0.05. MM-S and MM-VD correlated and agreed well with Riley shunt and with Bohr dead space. MM-S increased significantly after lung injury only in the lavage group, whereas MM-VD increased significantly in both groups. This is the first work evaluating and demonstrating the feasibility of near real-time VA/Q distribution measurements with the MIGET and the MMIMS methods.

Enhanced Quadrupole and Octupole Strength in Doubly Magic

The first 2^{+} and 3^{-} states of the doubly magic nucleus ^{132}Sn are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The ^{132}Sn ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a ^{206}Pb target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0_{g.s.}^{+}→2_{1}^{+}, 0_{g.s.}^{+}→3_{1}^{-}, and 2_{1}^{+}→3_{1}^{-} in ^{132}Sn. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0_{g.s.}^{+}→2_{1}^{+}) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of ^{132}Sn.

Sensitivity to change of the Dermatology Life Quality Index in adult females with facial acne vulgaris: a validation study.

BACKGROUND: The postadolescent form of acne papulopustulosa, also referred to as 'acne tarda' can have substantial negative impact on Quality of Life, especially in adult female patients. OBJECTIVE: Although the Dermatology Life Quality Index (DLQI) is widely used, empirical evidence about its performance in adult female acne patients is lacking. METHODS: In this prospective cohort study, we have investigated the sensitivity to change of the DLQI in 53 female adult acne patients with mild to moderate facial acne treated with azelaic acid (AzA) 15% gel twice daily over 24 weeks. RESULTS: Mean Investigator Static Global Assessment (ISGA) score was 2.3 (SD 0.5) at baseline and ranged from 0.9 (SD 0.3) to 2.1 (SD 0.4) at the end of the study in the 'Highly Improved' and 'Unchanged' responder groups respectively. The mean baseline DLQI score was 5.1 (SD 4.2). The Effect Size in the responder group 'Highly Improved' was 0.66; in group 'Improved' 0.62 and 0.23 in group 'Unchanged'. At the end of study, the mean DLQI score ranged from 1.1 (SD 1.5) in the 'Highly Improved' group to 3.7 (SD 6.0) in the 'Unchanged' group. CONCLUSION: The results support the sensitivity to change of the DLQI in this population.

[PCSK9 inhibitors : Current clinical relevance]. / PCSK9-Inhibitoren : Aktuelle klinische Bedeutung.

BACKGROUND: Hypercholesterolemias are known risk factors for cardiovascular diseases. Although statins have reduced the cardiovascular morbidity and mortality and further therapeutic measures are available, treatment goals are often not achieved. In cases of very high levels of low-density lipoprotein (LDL) cholesterol or of intolerability, the established therapies are often not sufficiently effective or cannot be used in adequate doses. For these high-risk patients further treatment options are required. OBJECTIVES: The current clinical relevance of the new substance class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the treatment of hypercholesterolemias is presented on the basis of the available data and the German regulations. CURRENT DATA: The two PCSK9 inhibitors, evolocumab and alirocumab, were approved in 2015. Data from many different patient groups are available for both substances. The significant reduction of LDL cholesterol of 50-60% and the very good tolerability and safety profile (at placebo level) are shown for both substances. The PCSK9 inhibitors are not as effective only in homozygous familial hypercholesterolemia. The first long-term data and one imaging study raise hope that the endpoint trials will show the expected reduction in cardiovascular events. Long-term trials have to show the long-term safety. In Germany it is legally regulated which patients can be treated by PCSK9 inhibitors and these prerequisites are largely in accordance with clinical practice. CONCLUSION: The body of evidence is rapidly increasing thereby facilitating the decision making when PCSK9 inhibitors could be used. The PCSK9 inhibitors will considerably improve the options for optimal treatment of high-risk patients.

[Erythematosquamous dermatoses in adolescence]. / Erythematosquamöse Erkrankungen in der Adoleszenz.

Erythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.

Selective Probing of the Penetration of Dexamethasone into Human Skin by Soft X-ray Spectromicroscopy.

Selective probing of dexamethasone in excised human skin using soft X-ray spectromicroscopy provides quantitative concentration profiles as well as two-dimensional drug distribution maps. Element- and site-selective excitation of dexamethasone at the oxygen K-edge with the lateral step width adjusted to 1 µm provides detailed information on the location of the drug in the different skin layers. The key of this work is to probe dexamethasone selectively at the carbonyl site (C3) by the O 1s → π* transition, providing also a most efficient way to quantify the drug concentration as a function of penetration depth in correlation with structural properties of the skin containing carboxyl and amide oxygen sites occurring at higher transition energy than dexamethasone. Following drug exposure for 4 h, the glucocorticoide is located in about equal amounts in the stratum corneum, the outermost horny layer of skin, and in the viable epidermis, whereas in the dermis no dexamethasone is detected. In the stratum corneum, most of the lipophilic drug is found in regions between corneocytes, where epidermal lipids are dominating.

Anomalous thermal contraction of the first coordination shell in metallic alloy liquids.

Except for a few anomalous solids and liquids, materials expand upon heating. For liquids, this should be reflected as a shift in the peak positions in the pair correlation function, g(r), to higher r. Here, we present the results of a detailed study of the volume thermal expansion coefficients and the temperature dependences of g(r) for a large number of binary, ternary, and quaternary liquids in the equilibrium and supercooled (metastable liquid below the liquidus temperature) states. The data were obtained from x-ray scattering and volume measurements on levitated liquids using the electrostatic levitation technique. Although the volumes of all liquids expand with increasing temperature, the peak positions in g(r) for the first coordination shells contract for the majority of alloy liquids studied. The second and third peaks in g(r) expand, but at rates different from those expected from the volume expansion. This behavior is explained qualitatively in terms of changes in the coordination numbers and bond-lengths as clusters in liquids break up with increasing temperature.

Ultraviolet radiation and nanoparticle induced intracellular free radicals generation measured in human keratinocytes by electron paramagnetic resonance spectroscopy.

BACKGROUND: Several nanoparticle-based formulations used in cosmetics and dermatology are exposed to sunlight once applied to the skin. Therefore, it is important to study possible synergistic effects of nanoparticles and ultraviolet radiation. METHODS: Electron paramagnetic resonance spectroscopy (EPR) was used to detect intracellular free radicals induced by ultraviolet B (UVB) radiation and amorphous silica nanoparticle and to evaluate the influence of nanoparticle surface chemistry on particle cytotoxicity toward HaCaT cells. Uncoated titanium dioxide nanoparticles served as positive control. In addition, particle intracellular uptake, viability, and induction of interleukin-6 were measured. RESULTS: We found that photo-activated titanium dioxide particles induced a significant amount of intracellular free radicals. On the contrary, no intracellular free radicals were generated by the investigated silica nanoparticles in the dark as well as under UVB radiation. However, under UVB exposure, the non-functionalized silica nanoparticles altered the release of IL-6. At the same concentrations, the amino-functionalized silica nanoparticles had no influence on UVB-induced IL-6 release. CONCLUSION: EPR spectroscopy is a useful technique to measure nanoparticle-induced intracellular free radicals. Non-toxic concentrations of silica particles enhanced the toxicity of UVB radiation. This synergistic effect was not mediated by particle-generated free radicals and correlated with particle surface charge and intracellular distribution.

[Methohexital for analgosedation of ventilated intensive care patients : prospective nonrandomized single center observational study on incidence of delirium]. / Methohexital zur Analgosedierung bei beatmeten Intensivpatienten : Prospektive nichtrandomisierte "Single-center"-Observationsstudie zur Delirinzidenz.

BACKGROUND: Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) as a potentially reversible disturbance of consciousness and a change of cognition caused by a medical condition, drug intoxication, or medication side effect. Delirium affects up to 80 % of intensive care unit (ICU) patients and is associated with increased morbidity and mortality. One risk factor for development of delirium in ventilated intensive care unit patients is sedation. The German S3 guidelines on "Analgesie, Sedierung und Delirmanagement in der Intensivmedizin" (analgesia, sedation and delirium management in intensive care medicine) of the DGAI (German Society for Anesthesiology and Intensive Care Medicine) and the DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine) recommend midazolam and propofol for sedation, although both drugs are associated with a high incidence of delirium. AIM: Within the framework of this study the question arose whether the barbiturate methohexital could be associated with a lower incidence of delirium in comparison to midazolam or propofol in analgosedated and ventilated ICU patients. MATERIAL AND METHODS: This was a prospective nonrandomized observational cohort study in a mixed medical surgical intensive care unit. Patients ventilated within 72 h after admittance were consecutively allocated to either propofol/remifentanil versus methohexital/remifentanil (expected ventilation duration ≤ 7 days) or midazolam/fentanyl versus methohexital/fentanyl (expected ventilation duration > 7 days) by the attending senior consultant anesthetist at the time of admission and/or intubation. Primary endpoint was delirium at any time during the ICU stay. Delirium was checked every 8 h by ICU nurses using the intensive care delirium screening checklist (ICDSC), with delirium defined as ICDSC ≥ 4 points. Before evaluation of the ICDSC the Richmond agitation sedation scale (RASS) score and the visual analogue scale for pain (VAS target ≤ 4) were measured. To assure reliable evaluation of the ICDSC, the RASS score of the patient at the time of evaluation had to be ≥ - 2. Assuming an incidence of delirium in the midazolam group of 70 % and in the methohexital group of 35 %, 16 patients were needed each in the midazolam/fentanyl and the methohexital/fentanyl cohorts (p = 0.05, ß = 0.1). Assuming an incidence of delirium in the propofol group of 50 % and in the methohexital group again of 35 %, 94 patients were needed in the propofol/remifentanil and methohexital/remifentanil groups, respectively (p = 0.05, ß = 0.1). RESULTS: A total of 222 patients were evaluated, 34 in the methohexital vs. midazolam group and 188 in the methohexital vs. propofol group. Out of 16 patients sedated with midazolam, 15 developed delirium (94 %) in contrast to only 5 out of 18 patients sedated with methohexital (28 %). Thus compared to midazolam the sedation with methohexital reduced the incidence of delirium by 66 % (p < 0.001) corresponding to a number needed to treat (NNT) of 1.5. Out of 94 patients in the propofol/remifentanil group, 64 developed delirium (68 %) in contrast to only 23 out of 94 in the methohexital/remifentanil group (24 %). Thus compared to propofol the sedation with methohexital reduced the incidence of delirium by 44 % (p < 0.001), corresponding to an NNT of 2.5. CONCLUSION: Sedation with methohexital compared to midazolam or propofol reduced the incidence of delirium by more than 50 % in ventilated ICU patients.

[Androgenetic alopecia. Diagnosis and therapy- a current review]. / Androgenetische Alopezie. Diagnostik und Therapie - eine aktuelle Übersicht.

Androgenetic alopecia (AGA) is among the most frequent diagnoses in a hair clinic. Multiple studies prove that life quality is significantly impaired in affected individuals, independent of severity, age or gender. A thorough and standardized diagnostic approach to AGA in women, men and children is an essential step in developing a successful therapeutic concept. Treatment options range from topical and systemic medications to cosmetic products, nutricosmetics, hair transplantation and other aesthetic-corrective approaches. The physician and patient must decide together on the best suited individualized therapy, considering the expected results, practicality and compliance. Further interdisciplinary evaluation must be decided individually, as must the development of coping strategies and the decision to employ psychological support. A professional atmosphere and sensitive approach to an emotionally difficult situation help develop a trusting relationship between patient and physician, which in turn leads to greater satisfaction and compliance. The S1 guidelines for diagnosis and the S3 guidelines for treatment of AGA offer the treating physician important tools for the successful evidence-based management of patients.

Are the elderly different? Factors influencing mortality after percutaneous coronary intervention with stent implantation.

BACKGROUND: The aim of this study was to investigate factors influencing mortality after percutaneous coronary intervention (PCI) in patients aged ≥ 75 years compared to younger patients. PATIENTS AND METHODS: A total of 1,809 coronary heart disease (CHD) patients after PCI with stent implantation in our hospital were assessed. Kaplan-Meier analyses with log-rank test and Cox regression analyses were performed on three predefined models concerning primary endpoint of all-cause mortality. Model 1 was a univariate analysis of the influence of age dichotomized by age 75 years on the primary endpoint. Model 2 included age and classical cardiovascular risk factors (CVRFs, e.g., body mass index (BMI), smoking, diabetes, and hypertension). Model 3 consisted of age, classical CVRFs, and additional factors (e.g., medication; hemoglobin, peripheral arterial disease (PAD), low-density lipoprotein cholesterol (LDL-C) and creatinine levels, and left ventricular ejection fraction (LVEF)). RESULTS: In the mean follow-up of 137 ± 61 weeks 375 patients died. Age ≥ 75 years was significantly related to mortality in all models. In model 3, previous stroke, PAD, diabetes, elevated levels of serum creatinine, and increased LDL-C were related to elevated mortality, higher hemoglobin levels, and LVEF > 50% were associated with decreased mortality in all patients and in patients < 75 years. In patients ≥ 75 years arterial hypertension was associated with poor outcome (hazard ratio (HR) 7.989, p = 0.040), previous antiplatelet therapy showed reduced mortality (HR 0.098, p = 0.039). CONCLUSION: Although risk factors such as previous stroke, PAD, diabetes, renal insufficiency, and anemia were predictors for death in all patients and patients < 75 years, in the elderly only arterial hypertension increased, whereas treatment with platelet inhibitors decreased mortality.

Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model.

Rapamycin, also known as Sirolimus, is a promising anti-proliferative drug, but its therapeutic use for the topical treatment of inflammatory, hyperproliferative skin disorders is limited by insufficient penetration rates due to its high molecular weight (MW of 914.172 g/mol) and high lipophilicity. We have shown that core multi-shell (CMS) nanocarriers sensitive to oxidative environment can improve drug delivery to the skin. In this study, we investigated the mTOR inhibitory activity of these oxidation-sensitive CMS (osCMS) nanocarrier formulations in an inflammatory ex vivo human skin model. In this model, features of inflamed skin were introduced by treating the ex vivo tissue with low-dose serine protease (SP) and lipopolysaccharide (LPS), while phorbol 12-myristate 13-acetate and ionomycin were used to stimulate IL-17A production in the co-cultured SeAx cells. Furthermore, we tried to elucidate the effects of rapamycin on single cell populations isolated from skin (keratinocytes, fibroblast) as well as on SeAx cells. Further, we measured possible effects of the rapamycin formulations on dendritic cell (DC) migration and activation. The inflammatory skin model enabled the assessment of biological readouts at both the tissue and T cell level. All investigated formulations successfully delivered rapamycin across the skin as revealed by reduced IL-17A levels. Nevertheless, only the osCMS formulations reached higher anti-inflammatory effects in the skin compared to the control formulations with a significant downregulation of mTOR activity. These results indicate that osCMS formulations could help to establish rapamycin, or even other drugs with similar physico-chemical properties, in topical anti-inflammatory therapy.

High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. METHODS: Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. RESULTS: Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). CONCLUSION: In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.

The location of paravertebral catheters placed using the landmark technique.

The aim of this prospective clinical study was to evaluate the location of paravertebral catheters that were placed using the classical landmark puncture technique and to correlate the distribution of contrast dye injected through the catheters with the extent of somatic block. Paravertebral catheter placement was attempted in 31 patients after video-assisted thoracic surgery. In one patient, an ultrasound-guided approach was chosen after failed catheter placement using the landmark method. A fluoroscopic examination in two planes using contrast dye was followed by injection of local anaesthetic and subsequent clinical testing of the extent of the anaesthetised area. In nine patients (29%), spread of contrast dye was not seen within the paravertebral space as intended. Misplaced catheters were in the epidural space (three patients), in the erector spinae musculature (five patients), and in the pleural space (one patient). There was also a discrepancy between the radiological findings and the observed distribution of loss of sensation. We have demonstrated an unacceptably high misplacement rate of paravertebral catheters using the landmark method. Additional research is required to compare the efficacy and safety of continuous paravertebral block using ultrasound-guided techniques or surgical inserted catheters.

[CorBene: a new model for collaborative care of patients with congestive heart failure]. / CorBene: Ein neues, kooperatives Versorgungsmodell für Patienten mit Herzinsuffizienz.

Congestive heart failure (CHF) is one of the most common medical disorders. The prognosis tends to be unfavorable and the quality of care needs further improvement. The aim of the CorBene project is to improve the health-related quality of life and the prognosis in patients in all stages of CHF and to reduce the hospitalization rate. For this purpose a modern collaborative treatment program involving all relevant health care professionals was developed. The key feature is the close collaboration between family physicians, practicing cardiologists, hospitals and rehabilitation facilities. The CorBene model was launched in Cologne and then spread to North-Rhine/Westphalia and to Saarland. Currently, there is the possibility to offer it in all German states. Preliminary analyses confirm an optimal, guideline-based therapy of CHF.