Publications by authors named "K Horst"

234 Publications

Surgical Excision Versus Neoadjuvant Radiotherapy Followed by Delayed Surgical Excision of Ductal Carcinoma In Situ (NORDIS).

Ann Surg Oncol 2021 Sep 2. Epub 2021 Sep 2.

Department of Surgery, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA, USA.

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http://dx.doi.org/10.1245/s10434-021-10552-7DOI Listing
September 2021

Imaging pediatric acute appendicitis during the coronavirus disease 2019 (COVID-19) pandemic: collateral damage is variable.

Pediatr Radiol 2021 Aug 17. Epub 2021 Aug 17.

Department of Radiology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.

Background: Since coronavirus disease 2019 (COVID-19) was declared a worldwide pandemic in March 2020, many authors have noted the collateral damage on non-COVID-19-related illnesses. These indirect effects of the pandemic have resulted in people presenting later and with more severe stages of disease, even if their diagnoses are not directly related to SARS-CoV-2, the virus that causes COVID-19.

Objective: We studied these indirect effects of COVID-19 on the imaging workup and outcomes for pediatric patients at our center who had acute appendicitis during the pandemic.

Materials And Methods: We performed a retrospective review of cases in children ≤18 years who were evaluated for acute appendicitis during the same period, March 1 to May 31, in both 2019 and 2020. We compared demographic and clinical data as well as surgical and pathological findings, and we graded imaging findings according to severity. Differences in patient outcomes were assessed using the Wilcoxon rank sum test and the Pearson chi-square test.

Results: The total number of pediatric patients evaluated with imaging for acute appendicitis dropped by 43% between 2019 and 2020 (298 vs. 169), but the total number of children treated remained similar (59 vs. 51). There was proportionate use of US and CT in each timeframe but a higher percentage of positive imaging findings in 2020 (50/169, 29.6% vs. 56/298, 18.7% in 2019, P=0.04). There were more imaging examinations with features of complicated appendicitis among positive cases (9/51, 18% vs. 5/59, 8% in 2019, P=0.08) and more pathologically proven perforated cases during the pandemic (14/51, 27% vs. 6/59, 10% in 2019, P=0.11), although these results did not reach statistical significance. There were no changes in surgical management, vital signs, laboratory values, length of stay or complication rates.

Conclusion: There was a large drop in the number of pediatric patients imaged for acute appendicitis during the acute phase of the COVID-19 pandemic despite similar numbers of patients treated. The utilization trends of US vs. CT remained stable between time periods. The differences in imaging findings and perforation rates were less pronounced compared to other published studies.
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http://dx.doi.org/10.1007/s00247-021-05128-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367768PMC
August 2021

The Influence of Macrophage-Activating Lipopeptide-2 in Regard to Liver-Specific Changes Within a Murine Two-Hit Model.

Inflammation 2021 Aug 16. Epub 2021 Aug 16.

Department of Orthopedic Trauma Surgery, RWTH Aachen University, Aachen, Germany.

Trauma hemorrhage (TH) and subsequent sepsis are well known to frequently result in severe organ damage. Although macrophage-activating lipopeptide-2 (MALP-2) has been described to exert beneficial effects on organ damage, and further clinical course after both isolated trauma and sepsis, little is known about the impact of MALP-2 in a clinically realistic two-hit scenario of TH and subsequent sepsis. As the liver represents a key organ for the posttraumatic immune response and development of complications, the effects of MALP-2 on the posttraumatic hepatic immunologic response and tissue damage were investigated in a murine "two-hit" model. In C57BL/6 mice, blood pressure-controlled (35 ± 5 mm Hg) TH was induced. Cecal ligation and puncture (CLP) was performed 48 h after TH. Mice were divided into two control groups (control 1, TH and laparotomy without CLP; control 2, TH and CLP) and three experimental groups (TH + CLP) treated with MALP-2 at different timepoints (ETH, end of TH; ECLP, end of CLP; 6CLP, 6 h after CLP). The observation time lasted for 168 h after induction of TH. Kupffer cells (KC) were isolated and cultured, and MPO activity was analyzed. Cell culture supernatants were taken for cytokine analysis (TNF-α, IL-6, MCP-1, GM-CSF, IL-10). Histological analysis was performed using the Hepatic Injury Severity Scoring (HISS). Statistical evaluation was carried out using SPSS (version 24.0.0; IBM, Armonk, NY, USA). MPO activity of control 1 group was lowest compared with all the other groups (p < 0.01). MPO activity of control 2 group was significantly higher than that in all experimental groups (ETH (p < 0.01), ECLP (p < 0.01), and 6CLP (p = 0.03)). Within the experimental groups, MPO activity was significantly reduced in the ETH (p = 0.04) and the ECLP (p < 0.01) groups compared with the 6CLP group. Moreover, ETH was also associated with the most pronounced reduction of cytokine expression by KC (p < 0.05). HISS revealed the largest damage in the group control 2. TH and subsequent sepsis lead to a distinct immunologic reaction in the liver with an increase of cytokine expression of KC and pronounced infiltration of granulocytes with associated severe tissue damage. MALP application decreases the hepatic immune response and liver damage, with the most pronounced effects if applied at the end of TH.
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http://dx.doi.org/10.1007/s10753-021-01534-8DOI Listing
August 2021

The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity.

Metabolism 2021 Oct 29;123:154839. Epub 2021 Jul 29.

Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands. Electronic address:

Background And Aims: Serotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We therefore aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity.

Methods: In this randomized controlled cross-over trial, we assessed the effects of 12 vs 24 h of fasting on SERT and DAT availability in the hypothalamus/thalamus and striatum, respectively, using SPECT imaging in 10 lean men and 10 men with obesity.

Results: As compared with the 12-h fast, a 24-h fast increased hypothalamic SERT availability in lean men, but not in men with obesity. We observed high inter-individual variation in the effects of fasting on thalamic SERT and striatal DAT, with no differences between lean men and those with obesity. In all subjects, fasting-induced increases in circulating free fatty acid (FFA) concentrations were associated with an increase in hypothalamic SERT availability and a decrease in striatal DAT availability. Multiple regression analysis showed that changes in plasma insulin and FFAs together accounted for 44% of the observed variation in striatal DAT availability.

Conclusion: Lean men respond to prolonged fasting by increasing hypothalamic SERT availability, whereas this response is absent in men with obesity. Inter-individual differences in the adaptations of the cerebral serotonergic and dopaminergic systems to fasting may, in part, be explained by changes in peripheral metabolic signals of fasting, including FFAs and insulin.
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http://dx.doi.org/10.1016/j.metabol.2021.154839DOI Listing
October 2021

Impact of anticoagulation and antiplatelet drugs on surgery rates and mortality in trauma patients.

Sci Rep 2021 Jul 26;11(1):15172. Epub 2021 Jul 26.

Department of Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.

Preinjury anticoagulation therapy (AT) is associated with a higher risk for major bleeding. We aimed to evaluated the influence of preinjury anticoagulant medication on the clinical course after moderate and severe trauma. Patients in the TraumaRegister DGU ≥ 55 years who received AT were matched with patients not receiving AT. Pairs were grouped according to the drug used: Antiplatelet drugs (APD), vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). The primary end points were early (< 24 h) and total in-hospital mortality. Secondary endpoints included emergency surgical procedure rates and surgery rates. The APD group matched 1759 pairs, the VKA group 677 pairs, and the DOAC group 437 pairs. Surgery rates were statistically significant higher in the AT groups compared to controls (APD group: 51.8% vs. 47.8%, p = 0.015; VKA group: 52.4% vs. 44.8%, p = 0.005; DOAC group: 52.6% vs. 41.0%, p = 0.001). Patients on VKA had higher total in-hospital mortality (23.9% vs. 19.5%, p = 0.026), whereas APD patients showed a significantly higher early mortality compared to controls (5.3% vs. 3.5%, p = 0.011). Standard operating procedures should be developed to avoid lethal under-triage. Further studies should focus on detailed information about complications, secondary surgical procedures and preventable risk factors in relation to mortality.
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http://dx.doi.org/10.1038/s41598-021-94675-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313576PMC
July 2021
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