Prehospital cooling with hypothermia caps (PreCoCa): a feasibility study

Background  Animal studies suggest that the induction of therapeutic hypothermia in patients after cardiac arrest should be initiated as soon as possible after ROSC to achieve optimal neuroprotective benefit. A “gold standard” for the method of inducing hypothermia quickly and safely has not yet been established. In order to evaluate the feasibility of a hypothermia cap we conducted a study for the prehospital setting. Methods and results  The hypothermia cap was applied to 20 patients after out-of-hospital cardiac arrest with a median of 10 min after ROSC (25/75 IQR 8–15 min). The median time interval between initiation of cooling and hospital admission was 28 min (19–40 min). The median tympanic temperature before application of the hypothermia cap was 35.5°C (34.8–36.3). Until hospital admission we observed a drop of tympanic temperature to a median of 34.4°C (33.6–35.4). This difference was statistically significant (P < 0.001). We could not observe any side effects related to the hypothermia cap. 25 patients who had not received prehospital cooling procedures served as a control group. Temperature at hospital admission was 35.9°C (35.3–36.4). This was statistically significant different compared to patients treated with the hypothermia cap (P < 0.001). Conclusions  In summary we demonstrated that the prehospital use of hypothermia caps is a safe and effective procedure to start therapeutic hypothermia after cardiac arrest. This approach is rapidly available, inexpensive, non-invasive, easy to learn and applicable in almost any situation. C. Storm & J.C. Schefold are equally contributing first authors. ClinicalTrials.gov Identifier: NCT00398671     

Reduction of neointimal hyperplasia in porcine coronary arteries by 2-deoxy-d-glucose

Background

The drug eluting stents have been shown to play a substantial role in preventing in-stent restenosis. This study was initiated to determine the efficacy of 2-deoxy-d-glucose (2-DG) in an in-stent restenosis model for reducing neointimal hyperplasia after coronary stent placement.

Methods

In a porcine overstretch model, three kinds of stents were investigated (n = 12 per group): bare metal stents (BMS), rapamycin-eluted stents (RES), and BMS after intracoronary short-term application of 2-DG (DGS). After 42 days histomorphometric and histopathological analyses were performed.

Results

Neointimal thickness (BMS: 0.38 ± 0.08, RES: 0.24 ± 0.11, DGS: 0.15 ± 0.01), area stenosis (BMS: 47.39 ± 2.76, RES: 32.2 ± 2.08, DGS: 29.30 ± 2.98) did not differ after 42 days between the RES and DGS but were significantly lower as compared to BMS only. Lumen area (BMS: 3.15 ± 1.53, RES: 4.37 ± 1.72, DGS: 4.77 ± 2.14) was significantly higher in the DGS group in comparison to the BMS group. The calculated injury and inflammation scores were similar and re-endothelialization was confirmed in all groups.

Conclusions

This study could demonstrate that in porcine stent model neointimal hyperplasia and re-endothelialization after application of 2-DG are comparable to those seen in RES. Thus, 2-DG might be a promising clinical application for coronary stent coating.     

TIMP-1 signaling via CD63 triggers granulopoiesis and neutrophilia in mice

The homeostasis of neutrophil granulocytes can affect the outcome of several inflammation-associated diseases including cancer. The regulation of this homeostasis is still not completely understood. We previously found that elevated systemic levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) induce an increase of neutrophils in the liver, which in turn strongly promotes liver metastasis. Here, we report that increasing systemic TIMP-1 levels were sufficient to induce neutrophilia in mice. This was not attributed to prolonged survival or direct mobilization of neutrophils. However, TIMP-1 induced enrichment of myeloid progenitors and concomitant upregulation of granulopoiesis-associated genes in the bone marrow compartment. BrdU pulse-labeling confirmed that proliferating progenitors accounted for TIMP-1-induced neutrophilia. TIMP-1 variants that dissect its protease-inhibitory from its CD63 binding function relevant for cell signaling revealed that the TIMP-1 signaling domain was necessary and sufficient to augment granulopoiesis. Consequently, ablation of the TIMP-1 receptor CD63 abolished both neutrophilia and TIMP-1-enhanced granulopoiesis in the bone marrow. Our findings reveal that elevated levels of TIMP-1 impact on neutrophil homeostasis via signaling through CD63. This may provide a link to clinical observations, where TIMP-1 correlates with high severity and bad prognosis in inflammation-associated diseases.     

Correlation of signal intensity ratio on orbital MRI-TIRM and clinical activity score as a possible predictor of therapy response in Graves’ orbitopathy—a pilot study at 1.5 T

Introduction  

This study seeks to describe the predictive value of the signal intensity ratio (SIR) in magnetic resonance imaging-turbo inversion recovery magnitude (MRI-TIRM) in patients with Graves’ orbitopathy (GO) with regard to predictability of therapy response.     

Update Breast Cancer 2020 Part 5 – Moving Therapies From Advanced to Early Breast Cancer Patients

In recent years, significant progress has been made in new therapeutic approaches to breast cancer, particularly in patients with HER2-positive and HER2-negative/hormone receptor-positive (HR+) breast cancer. In the case of HER2-positive tumours, these approaches have included, in particular, treatment with pertuzumab, T-DM1, neratinib and, soon, also tucatinib and trastuzumab deruxtecan (neither of which has yet been authorised in Europe). In patients with HER2−/HR+ breast cancer, CDK4/6 inhibitors and the PIK3CA inhibitor alpelisib are of particular importance. Further novel therapies, such as Akt kinase inhibitors and oral SERDs (selective estrogen receptor down regulators), are already being investigated in ongoing clinical trials. These therapeutic agents are not only being introduced into curative, (neo-)adjuvant therapeutic settings for HER2-positive tumours; a first favourable study on abemaciclib as an adjuvant therapy has now also been published. In patients with triple-negative breast cancer, after many years of negative study results with the Trop-2 antibody drug conjugate (ADC) sacituzumab govitecan, a randomised study has been published that may represent a significant therapeutic advance. This review describes the latest developments in breast cancer subsequent to the ESMO Congress 2020.Key words: early breast cancer, therapy, prognosis, immune therapy, digital medicine