A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe

STUDY QUESTION: How did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? SUMMARY ANSWER: MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. WHAT IS KNOWN ALREADY: With the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. STUDY DESIGN, SIZE, DURATION: A structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. PARTICIPANTS/MATERIALS, SETTING, METHODS: The information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. MAIN RESULTS AND THE ROLE OF CHANCE: By aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. WIDER IMPLICATIONS OF THE FINDINGS: The current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations.peer-reviewe

Antimicrobial effect and biocompatibility of novel metallic nanocrystalline implant coatings

Aim The present in vitro study was designed to evaluate the surface characteristics, biocompatibilities and antimicrobial effects of experimental titanium implant surfaces, coated by nanocrystalline silver, copper, and bismuth. Biocompatible and antimicrobial implant modifications could result in reduced biofilm formation on implant surfaces and therefore in less periimplant inflammation. Findings Titanium discs (thickness 1 and 12 mm in diameter) were coated by pulsed magnetron-sputtering of nanocrystalline metals (bismuth, copper, and silver). Bismuth coatings revealed higher surface roughness values in comparison to silver and copper coatings via atomic force microscopy. Ion release after 168 h in culture medium was analyzed by inductively coupled plasma-mass spectrometry and showed significant different amounts of released copper (>120 000 µg/L), silver (550 µg/L) or bismuth (80 µg/L). No cytotoxic effect on HaCaT cell proliferation was detected on the uncoated Ti/TiO2 reference surfaces, the bismuth coatings and silver coatings. In contrast, Cu-coated discs showed a strong cytotoxic effect. All three coatings exhibited antimicrobial effects by trend in the fluorometric Resazurin testing and significant localized antibacterial effects in live/dead microscopy after incubation of the specimens for 150 min in bacterial solution of S. epidermidis. Conclusions The tested metallic implant coatings (silver and bismuth) allowed surface modifications that may improve therapeutic approaches to biofilm prevention on dental implants

Early Decompression (< 8 h) after Traumatic Cervical Spinal Cord Injury Improves Functional Outcome as Assessed by Spinal Cord Independence Measure after One Year

There is an ongoing controversy about the optimal timing for surgical decompression after acute traumatic cervical spinal cord injury (SCI). For this reason, we performed a retrospective study of patients who were operated on after traumatic cervical SCI at the Trauma Center Murnau, Germany, and who met inclusion as well as exclusion criteria (n = 70 patients). Follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury (EMSCI) protocol over a period of 1 year. Early decompression was defined as within the first 8 h after the insult (n = 35 patients). Primary outcome was the difference in the SCIM (Spinal Cord Independence Measure) 1 year after the trauma. After the follow-up period, patients who were decompressed earlier had a significantly higher SCIM difference (45.8 vs. 27.1, p < 0.005). A regression analysis showed that timing of decompression, age, as well as basal AIS (American Spinal Injury Association Impairment Scale) and basal SCIM scores were independent predictors for a better functional outcome (SCIM). Further, patients from the early decompression group had better AIS grades (p < 0.006) and a higher AIS conversion rate (p < 0.029). Additionally, this cohort also had a better total motor performance as well as upper extremity motor function after 1 year (p < 0.025 and p < 0.002). The motor and neurological levels of patients who were operated on within 8 h were significantly more caudal (p < 0.003 and p < 0.014) after 1 year. The present study suggests that early decompression after traumatic cervical SCI might have a positive impact on the functional and neurological outcome of affected individuals

Pharmacological HIF-inhibition attenuates postoperative adhesion formation

Abstract Peritoneal adhesions represent a common complication of abdominal surgery, and tissue hypoxia is a main determinant in adhesion formation. Reliable therapeutic options to reduce peritoneal adhesions are scarce. We investigated whether the formation of postsurgical adhesions can be affected by pharmacological interference with hypoxia-inducible factors (HIFs). Mice were treated with a small molecule HIF-inhibitor, YC-1 (3-[5′-Hydroxymethyl-2′-furyl]-1-benzyl-indazole), or vehicle three days before and seven days after induction of peritoneal adhesions or, alternatively, once during induction of peritoneal adhesions. Pretreatment or single intraperitoneal lavage with YC-1 significantly reduced postoperative adhesion formation without prompting systemic adverse effects. Expression analyses of cytokines in peritoneal tissue and fluid and in vitro assays applying macrophages and peritoneal fibroblasts indicated that this effect was cooperatively mediated by various putatively HIF-1α-dependent mechanisms, comprising attenuated pro-inflammatory activation of macrophages, impaired recruitment and activation of peritoneal fibroblasts, mitigated epithelial-mesenchymal-transition (EMT), as well as enhanced fibrinolysis and impaired angiogenesis. Thus, this study identifies prevention of postsurgical peritoneal adhesions as a novel and promising field for the application of HIF inhibitors in clinical practice

Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ) chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group) and 30 patients received radiotherapy alone (RT group). The most common aberrations detected were gains of parts of chromosome 7 and losses of 10q, 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months). Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas

Pharmacologic inhibition of hypoxia inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis

BACKGROUND: When an immune cell migrates from the bloodstream to a site of chronic inflammation, it experiences a profound decrease in microenvironmental oxygen levels leading to a state of cellular hypoxia. The hypoxia-inducible factor-1α (HIF-1α) promotes an adaptive transcriptional response to hypoxia and as such is a major regulator of immune cell survival and function. HIF hydroxylases are the family of oxygen-sensing enzymes primarily responsible for conferring oxygen-dependence upon the HIF pathway. METHODS: Using a mouse model of allergic contact dermatitis (ACD), we tested the effects of treatment with the pharmacologic hydroxylase inhibitor DMOG, which mimics hypoxia, on disease development. RESULTS: Re-exposure of sensitized mice to 2,4-dinitrofluorobenzene (DNFB) elicited inflammation, edema, chemokine synthesis (including CXCL1 and CCL5) and the recruitment of neutrophils and eosinophils. Intraperitoneal or topical application of the pharmacologic hydroxylase inhibitors dymethyloxalylglycine (DMOG) or JNJ1935 attenuated this inflammatory response. Reduced inflammation was associated with diminished recruitment of neutrophils and eosinophils but not lymphocytes. Finally, hydroxylase inhibition reduced cytokine-induced chemokine production in cultured primary keratinocytes through attenuation of the JNK pathway. CONCLUSION: These data demonstrate that hydroxylase inhibition attenuates the recruitment of neutrophils to the inflamed skin through reduction of chemokine production and increased neutrophilic apoptosis. Thus, pharmacologic inhibition of HIF hydroxylases may be an effective new therapeutic approach in allergic skin inflammation. This article is protected by copyright. All rights reserved

Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers

The modulation of macrophage phenotype from a pro-inflammatory to an anti-inflammatory state holds therapeutic potential in the treatment of inflammatory disease. We have previously shown that arginase-2 (Arg2), a mitochondrial enzyme, is a key regulator of the macrophage anti-inflammatory response. Here, we investigate the therapeutic potential of Arg2 enhancement via target site blockers (TSBs) in human macrophages. TSBs are locked nucleic acid antisense oligonucleotides that were specifically designed to protect specific microRNA recognition elements (MREs) in human ARG2 3' UTR mRNA. TSBs targeting miR-155 (TSB-155) and miR-3202 (TSB-3202) MREs increased ARG2 expression in human monocyte-derived macrophages. This resulted in decreased gene expression and cytokine production of TNF-α and CCL2 and, for TSB-3202, in an increase in the anti-inflammatory macrophage marker, CD206. Proteomic analysis demonstrated that a network of pro-inflammatory responsive proteins was modulated by TSBs. In silico bioinformatic analysis predicted that TSB-3202 suppressed upstream pro-inflammatory regulators including STAT-1 while enhancing anti-inflammatory associated proteins. Proteomic data were validated by confirming increased levels of sequestosome-1 and decreased levels of phosphorylated STAT-1 and STAT-1 upon TSB treatment. In conclusion, upregulation of Arg2 by TSBs inhibits pro-inflammatory signaling and is a promising novel therapeutic strategy to modulate inflammatory signaling in human macrophages. </p