LVR-Klinik für Orthopädie Viersen

We performed multiomic factor analysis of biomarkers potentially associated with pathologic complete response (pCR) after a chemotherapy-free combination of immunotherapy and dual ERBB2 (HER2) blockade. Forty-eight patients with HER2 2+ (ISH+) or 3+ early breast cancer, stage I to III, and HER2-enriched subtype received pembrolizumab, trastuzumab biosimilar, and pertuzumab. The primary outcome was pCR (ypT0/is ypN0). Multiomic factors representing combined markers from pooling different translational research marker data were identified based on the eigenvalue >1 criteria. Additionally, logistic regressions with elastic net regularization were performed using all single markers, multiomic factors, and clinical characteristics to evaluate their association with pCR. The multiomic factor involving genes related to immune response and tumorigenesis, multiplexed IHC markers related to immune response and HER2 in the stroma, and stromal tumor-infiltrating lymphocytes were associated with pCR. pCR rates were 66.7% and 28.6% in the high (>median) and low (≤median) factor score groups, respectively (unadjusted OR, 5.00; 95% confidence interval, 1.35-18.56; nominal P = 0.016). In the analysis using standardized values for all individual markers from gene expression analysis, multiplexed IHC analysis in the stroma, and stromal tumor-infiltrating lymphocytes, markers with the greatest impact on pCR were the genes FNBP1, CD36, MYCN, and SIX1 (OR between 1.43 and 1.62), and progesterone receptor status (OR, 0.65), which surpassed grade (OR, 1.22) and nodal status (OR, 0.90). Our multiomic analysis uncovered mechanisms of tumor response to immunotherapy combined with dual HER2 blockade. These results could inform the design of larger trials investigating chemotherapy-free regimens in selected patients with HER2+ early breast cancer.

For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

The technology envisioned in the DeepU project (Deep U-tube heat exchanger) is expected to revolutionize the geothermal energy sector, increasing the accessibility of deep geothermal resources for low-carbon heating and power generation. The ultimate project goal is to create a deep (&gt;4 km) closed-loop connection in the shape of a U-tube exchanger by developing a fast and effective laser drilling technology. The project comprises the development of a novel drilling technique and its application via geothermal modeling at selected sites. A prototype of a drill-head has been realized, combining the laser system with drill strings, sustaining the coupled action of laser and cryogenic gas. The fine particles of drilled rocks are ejected to the surface in the gas stream via the borehole annulus. This contribution focuses on the project&amp;#8217;s activities related to the laser-rock interactions studied in the experimental laser drilling tests based on previous works (Seo et al., 2022; Li et al., 2022a, 2022b). Three types of lithologies were selected for initial laboratory tests: granite, sandstone, and limestone (50 x 35 x 15 cm). Constant rates of penetration (ROP) upwards of 20 m/h have been achieved in all lithologies with borehole diameter reaching 18 cm. The petro-thermo-mechanical phenomena occurring during laser drilling, such as spallation, melting, and evaporation, were recognized and described. The drilling process was investigated by thermocamera imaging providing information about the most effective process induced by heating the rocks, up to 700&amp;#176;C. The laser working parameters and experimental setup were optimized regarding observed phenomena. In the next step, sections of boreholes were cut out and examined. The microscopic observations on the thermal unaffected and affected rocks&amp;#8217; thin sections have been performed with the use of polarized optical microscopy and scanning electron microscopy revealing micro-fracturing patterns of the rock induced on rock samples by the heating processes. The change of physic-mechanical properties of rocks was investigated and acknowledged in geothermal models. This innovative and comprehensive study revealed macro- and micro-scale phenomena occurring during laser drilling, contributing to the successful development of this new drilling method and subsequently its application for exploitation of geothermal energy from depths below 4 km. This research is funded by the European Union (G.A. 101046937). However, the views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or EISMEA. Neither the European Union nor the granting authority can be held responsible for them.

Objectives: The aim of this clinical trial was to explore whether psychodynamic-interactional therapy leads to a better outcome in the treatment of somatoform pain disorders when combined with body therapy. Methods: 30 patients diagnosed with this disorder took part in outpatient group therapies with 25 sessions. In the intervention condition, sessions based on psychodynamic-interactional and body therapy took place in weekly change, while in the control condition all sessions were based on psychodynamic-interactional therapy. Data were collected with self-report measures at the beginning and end of therapy and at the 6-months follow-up. Results: Under both conditions somatic and psychological symptoms merely remained stable from the first to the third measurement time. However, patients expressed a high level of satisfaction with the relationships in the group. Conclusions: Contrary to the assumptions, the two therapy conditions did not differ in the treatment outcome. Both conditions proved successful in providing patients with supporting interpersonal experiences.

Correction to: Lithium Therapy in Old Age: Recommendations from a Delphi SurveyPharmacopsychiatry eFirstDOI: 10.1055/a-2117-5200