Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.

Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing. Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile. Design, Setting, and Participants: This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1/2 mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21 711 months was available, with 336 PFS and 245 OS events. Exposures: Tumor homologous recombination deficiency was assessed using the BRCA-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and bevacizumab and placebo plus bevacizumab groups. Main Outcomes and Measures: This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression. Results: A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n = 138) harbored a pathogenic BRCA mutation, and BRCA-like classification was performed for 442 patients. Patients with a BRCA-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P < .001). No association of olaparib with PFS was found in patients with a non-BRCA-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P = .93). The interaction was significant (P = .004), and HRs and P values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses. Conclusions and Relevance: In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non-BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.

The association of histopathologic features after neoadjuvant chemo-immunotherapy with clinical outcome: Sub-analyses from the randomized double-blinded, placebo-controlled, Phase III IMagyn050/GOG3015/ENGOT-ov39 study.

OBJECTIVE: Histopathologic characteristics after neoadjuvant chemotherapy (NACT) may correlate with outcome. This study evaluates histopathologic features after immunotherapy and NACT/bevacizumab, and associated clinical outcomes. METHODS: Evaluable tissue from IMagyn050/GOG3015/ENGOT-ov39 patients from prespecified anatomic sites from interval cytoreductive surgery (ICS) after NACT/bevacizumab plus atezolizumab/placebo underwent central histopathologic scoring and analyzed with clinical outcomes. RESULTS: The predefined population had 243 evaluable NACT patients, with 48.1% tumors being PD-L1-positive. No statistically significant differences in PFS (16.9 months vs. 19.2 months, p = 0.21) or OS (41.5 months vs. 45.1 months, p = 0.67) between treatment arms were seen. Substantial residual tumor (RT) (3+) was identified in 26% atezolizumab vs. 24% placebo arms (p = 0.94). Most showed no (1+) necrosis (82% vs. 96%, respectively, p = 0.69), moderate (2+) to severe (3+) fibrosis (71% vs. 75%, respectively, p = 0.82), and extensive (2+) inflammation (53% vs. 47% respectively, p = 0.48). No significant histopathologic differences were identified by tissue site or by arm. Multivariate analyses showed increased risk for progression with moderate and substantial RT (13.6 mon vs. 21.1 mon, hazard ratio 2.0, p < 0.01; 13.6 mon vs. 21.1 mon, HR 1.9, p < 0.01, respectively); but decreased risk for death with extensive inflammation (46.9 mon vs. 36.3 mon, HR 0.65, p = 0.02). Inflammation also correlated with greater likelihood of response to NACT/bevacizumab plus immunotherapy (odds ratio 2.9, p < 0.01). Modeling showed inflammation as a consistent but modest predictor for OS. CONCLUSIONS: Detailed histologic assessment of ICS specimens appear to identify characteristics, such as inflammation and residual tumor, that may provide insight to certain clinical outcomes. Future work potentially leveraging emerging tools may provide further insight into outcomes.

Six-minute walking distance and desaturation-distance ratio in allogeneic stem cell transplantation.

BACKGROUND: Most patients with haematological malignancies who undergo allogeneic haematopoietic stem cell transplant (HSCT) receive chemotherapy before the transplant to control the disease. Certain chemotherapy drugs can cause lung toxicity. Conversely, in patients with chronic respiratory conditions, the 6-min walking test (6MWT) and the desaturation-distance ratio (DDR) have demonstrated prognostic significance. Our objective was to determine whether the 6MWD and DDR, assessed prior to HSCT, have a prognostic impact on survival at 24 months post-HSCT. METHODS: A prospective experimental study was conducted in consecutive patients referred for allogeneic HSCT at Hospital Clinic, Barcelona, Spain. A complete functional respiratory study, including the 6MWT and DDR, was conducted prior to admission. The area under the curve (AUC) and cut-off points were calculated. Data on patients' characteristics, HSCT details, main events, with a focus on lung complications, and survival at 24 months were analysed. RESULTS: One hundred and seventy-five patients (39% women) with mean age of 48 ± 13 years old were included. Before HSCT, forced vital capacity and forced expiratory volume in the first second were 96% ± 13% predicted and 92% ± 14% predicted, respectively; corrected diffusing capacity for carbon monoxide 79% ± 15% predicted; 6MWD was 568 ± 83 m and DDR of .27 (.20-.41). The cut-off points for 6MWD and DDR were 566 m, [.58 95% CI (.51-.64)], p = .024 and .306, [.63 95% CI (.55-.70)], p = .0005, respectively. The survival rate at 24 months was 55%. CONCLUSION: Our results showed that individuals who exhibit a 6MWD shorter than 566 ms or a decline in DDR beyond .306 experienced reduced survival rates at 24 months after HSCT.

Impact of Argemone mexicana L. on tomato plants infected with Phytophthora infestans.

Background: Fungal diseases can cause significant losses in the tomato crop. Phytophthora infestans causes the late blight disease, which considerably affects tomato production worldwide. Weed-based plant extracts are a promising ecological alternative for disease control. Methods: In this study, we analyzed the plant extract of Argemone mexicana L. using chromatography-mass spectrometry analysis (GC-MS). We evaluated its impact on the severity of P. infestans, as well as its effect on the components of the antioxidant defense system in tomato plants. Results: The extract from A. mexicana contains twelve compounds most have antifungal and biostimulant properties. The findings of the study indicate that applying the A. mexicana extract can reduce the severity of P. infestans, increase tomato fruit yield, enhance the levels of photosynthetic pigments, ascorbic acid, phenols, and flavonoids, as well as decrease the biosynthesis of H2O2, malondialdehyde (MDA), and superoxide anion in the leaves of plants infected with this pathogen. These results suggest that using the extract from A. mexicana could be a viable solution to control the disease caused by P. infestans in tomato crop.

Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/MINOVA Study).

PURPOSE: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. EXPERIMENTAL DESIGN: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. RESULTS: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells, and an upregulation in effector/regulatory cell ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS). CONCLUSIONS: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4+, CD8+ lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer. See related commentary by Soberanis Pina and Oza, p. 12.

Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer.

BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. RESULTS: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). CONCLUSIONS: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

Changes to women's childbirth plans during the COVID-19 pandemic and posttraumatic stress symptoms: a cross-national study.

A considerable number of women giving birth during COVID-19 pandemic reported being concerned about changes to their childbirth plans and experiences due to imposed restrictions. Research prior to the pandemic suggests that women may be more at risk of post-traumatic stress symptoms (PTSS) due to unmet expectations of their childbirth plans. Therefore, this study aimed to examine if the mismatch between women's planned birth and actual birth experiences during COVID-19 was associated with women's postpartum PTSS. Women in the postpartum period (up to 6 months after birth) across 11 countries reported on childbirth experiences, mental health, COVID-19-related factors, and PTSS (PTSD checklist DSM-5 version) using self-report questionnaires (ClinicalTrials.gov: NCT04595123). More than half (64%) of the 3532 postpartum women included in the analysis reported changes to their childbirth plans. All changes were significantly associated with PTSS scores. Participants with one and two changes to their childbirth plans had a 12% and 38% increase, respectively, in PTSS scores compared to those with no changes (Exp(ß) = 1.12; 95% CI [1.06-1.19]; p < 0.001 and Exp(ß) = 1.38; 95% CI [1.29-1.48]; p < 0.001). In addition, the effect of having one change in the childbirth plan on PTSS scores was stronger in primigravida than in multigravida (Exp(ß) = 0.86; 95% CI [0.77-0.97]; p = 0.014). Changes to women's childbirth plans during the COVID-19 pandemic were common and associated with women's postpartum PTSS score. Developing health policies that protect women from the negative consequences of unexpected or unintended birth experiences is important for perinatal mental health.

Eficacia y seguridad de la administración de plasma de convaleciente en pacientes con COVID-19 / Efficacy and safety of convalescent plasma administration in patients with COVID-19 infection

Introducción Durante la pandemia de COVID-19 surgieron diversas estrategias para el manejo de la enfermedad, incluidos los tratamientos farmacológicos y no farmacológicos como el plasma convaleciente (PC). El uso de PC se sugirió debido a los resultados benéficos mostrados al tratar otras enfermedades virales. Objetivo Determinar la eficacia y la seguridad de la administración de PC obtenido de sangre total en pacientes con COVID-19. Métodos Ensayo clínico piloto en pacientes con COVID-19 de un hospital general. Los sujetos se separaron en 3 grupos que recibieron la transfusión de 400ml de PC (n=23) o 400ml de plasma estándar (PE) (n=19) y un grupo no transfundido (NT) (n=37). Los pacientes recibieron además, el tratamiento médico estándar disponible para COVID-19. El seguimiento de los sujetos se llevó a cabo diariamente desde el ingreso hasta el día 21. Resultados El PC no mejoró la curva de supervivencia en las variantes moderadas y graves de COVID-19, ni disminuyó el grado de severidad de la enfermedad evaluado con la escala de progresión clínica COVID-19, OMS y SOFA. Ningún paciente presentó una reacción postransfusional severa al PC. Conclusiones El tratamiento con PC no disminuye la mortalidad de los pacientes, aun cuando su administración tiene un alto grado de seguridad (AU)

Introduction During the COVID-19 pandemic, several strategies were suggested for the management of the disease, including pharmacological and non-pharmacological treatments such as convalescent plasma (CP). The use of CP was suggested due to the beneficial results shown in treating other viral diseases. Objective To determine the efficacy and safety of CP obtained from whole blood in patients with COVID-19. Methods Pilot clinical trial in patients with COVID-19 from a general hospital. The subjects were separated into three groups that received the transfusion of 400ml of CP (n=23) or 400ml of standard plasma (SP) (n=19) and a non-transfused group (NT) (n=37). Patients also received the standard available medical treatment for COVID-19. Subjects were followed up daily from admission to day 21. Results The CP did not improve the survival curve in moderate and severe variants of COVID-19, nor did it reduce the degree of severity of the disease evaluated with the COVID-19 WHO and SOFA clinical progression scale. No patient had a severe post-transfusion reaction to CP. Conclusions Treatment with CP does not reduce the mortality of patients even when its administration has a high degree of safety (AU)

[Efficacy and safety of convalescent plasma administration in patients with COVID-19 infection]. / Eficacia y seguridad de la administración de plasma de convaleciente en pacientes con COVID-19.

INTRODUCTION: During the COVID-19 pandemic, several strategies were suggested for the management of the disease, including pharmacological and non-pharmacological treatments such as convalescent plasma (CP). The use of CP was suggested due to the beneficial results shown in treating other viral diseases. OBJECTIVE: To determine the efficacy and safety of CP obtained from whole blood in patients with COVID-19. METHODS: Pilot clinical trial in patients with COVID-19 from a general hospital. The subjects were separated into three groups that received the transfusion of 400ml of CP (n=23) or 400ml of standard plasma (SP) (n=19) and a non-transfused group (NT) (n=37). Patients also received the standard available medical treatment for COVID-19. Subjects were followed up daily from admission to day 21. RESULTS: The CP did not improve the survival curve in moderate and severe variants of COVID-19, nor did it reduce the degree of severity of the disease evaluated with the COVID-19 WHO and SOFA clinical progression scale. No patient had a severe post-transfusion reaction to CP. CONCLUSIONS: Treatment with CP does not reduce the mortality of patients even when its administration has a high degree of safety.

Graphene-Cu Nanocomposites Induce Tolerance against Fusarium oxysporum, Increase Antioxidant Activity, and Decrease Stress in Tomato Plants.

The tomato crop is susceptible to various types of stress, both biotic and abiotic, which affect the morphology, physiology, biochemistry, and genetic regulation of plants. Among the biotic factors, is the phytopathogen Fusarium oxysporum f. sp. lycopersici (Fol), which can cause losses of up to 100%. Graphene-Cu nanocomposites have emerged as a potential alternative for pathogen control, thanks to their antimicrobial activity and their ability to induce the activation of the antioxidant defense system in plants. In the present study, the effect of the Graphene-Cu nanocomposites and the functionalization of graphene in the tomato crop inoculated with Fol was evaluated, analyzing their impacts on the antioxidant defense system, the foliar water potential (Ψh), and the efficiency of photosystem II (PSII). The results demonstrated multiple positive effects; in particular, the Graphene-Cu nanocomposite managed to delay the incidence of the "vascular wilt" disease and reduce the severity by 29.0%. This translated into an increase in the content of photosynthetic pigments and an increase in fruit production compared with Fol. In addition, the antioxidant system of the plants was improved, increasing the content of glutathione, flavonoids, and anthocyanins, and the activity of the GPX, PAL, and CAT enzymes. Regarding the impact on the water potential and the efficiency of the PSII, the plants inoculated with Fol and treated with the Graphene-Cu nanocomposite responded better to biotic stress compared with Fol, reducing water potential by up to 31.7% and Fv/Fm levels by 32.0%.

Optimization of Paenibacillus sp. NMA1017 Application as a Biocontrol Agent for Phytophthora tropicalis and Moniliophthora roreri in Cacao-Growing Fields in Chiapas, Mexico.

In Mexico, cacao production is endangered by pathogenic fungi, such as Phytophthora spp. and Moniliophthora rorei, that cause black pod rot and moniliasis, respectively. In this study the biocontrol agent Paenibacillus sp. NMA1017 was tested in cacao fields against the previous diseases. The treatments applied were shade management, inoculation of the bacterial strain with or without an adherent, and use of chemical control. The statistical analysis showed that the incidence of black pod rot in tagged cacao trees diminished when the bacterium was applied (reduction of 44.24 to 19.11%). The same result was observed with moniliasis when the pods were tagged (reduction of 66.6 to 27%). The use of Paenibacillus sp. NMA1017 with an integrated management might be a solution to cacao diseases and to having a sustainable production of cacao in Mexico.

Predictive factors for anti-MDA5 antibody in patients with dermatomyositis: a retrospective multicenter study.

BACKGROUND AND OBJECTIVES: Melanoma differentiation-associated gene 5 antibody (anti-MDA5) in dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease and poor prognosis. Early diagnosis is key to improving the prognosis of these patients. The aim was to confirm cutaneous characteristics in patients with anti-MDA5 dermatomyositis and to explore new diagnostic markers for the presence of anti-MDA5 (anti-MDA5+ ). PATIENTS AND METHODS: A multicenter cross-sectional retrospective cohort study of 124 patients diagnosed with DM, of which 37 were anti-MDA5+ . Demographic data, laboratory data, and clinical manifestations were collected. RESULTS: Anti-MDA5+ DM is characterized by a distinct mucocutaneous phenotype that includes oral lesions, alopecia, mechanic's hands, palmar and dorsal papules, palmar erythema, vasculopathy, and skin ulceration. We found vasculopathy and digit tip involvement very frequently in anti-MDA5+ patients (p <0.001), being a diagnostic marker of anti-MDA5+ (OR, 12.355; 95% CI 2.850-79.263; p  =  0.012 and OR, 7.447; 95% CI 2.103-46.718; p  =  0.004, respectively). The presence of ulcers deserves special mention, especially in anti-MDA5+ patients, because in our cohort, up to 97% of the anti-MDA5+ patients had ulcers. CONCLUSIONS: In patients with suspected DM with digit tip involvement or vasculopathy, the presence of anti-MDA5 antibodies must be ruled out, as it may be a clinical predictor.

Clinical and molecular signature of survival and resistance to olaparib plus pegylated liposomal doxorubicin in platinum-resistant ovarian cancer: a stratified analysis from the phase II clinical trial ROLANDO, GEICO-1601.

OBJECTIVE: To determine the potential prognostic value of clinical and molecular biomarkers in the survival of patients with platinum-resistant ovarian cancer treated with olaparib and pegylated liposomal doxorubicin. METHODS: ROLANDO was a single-arm phase II trial that included patients with high-grade serous or endometrioid tumors and at least one previous platinum-resistant recurrence regardless of BRCA status. Patients received 6 cycles of pegylated liposomal doxorubicin every 28 days plus olaparib 300 mg twice daily. followed by olaparib 300 mg twice daily; monotherapy until progression or unacceptable toxicity. Prognostic factors including previous lines (and platinum-containing ones), BRCA mutation status, previous bevacizumab, CA-125 levels, and the neutrophil/lymphocyte ratio, lymphocyte/monocyte ratio, and platelet/lymphocyte ratio calculated at inclusion were analyzed through a multivariate logistic regression and factor analysis of mixed data. RESULTS: Thirty-one patients were included. Median age was 57 years (range 43-75), Eastern Cooperative Oncolgy Group performance status 0/1: 32.3%/67.7% and BRCA mutated: 16.1%. Prior treatment lines were >2 lines: 14 (45.2%) patients, ≥2 platinum lines: 21 patients (67.7%) and previous bevacizumab 19 (61.3%) patients. CA-125 was >2 upper limit normal in 24 (77.4%) patients. A high neutrophil/lymphocyte ratio was associated with worse overall survival by univariate/multivariate regression model (HR=11.18; 95% CI 1.1 to 114.5; p=0.042). No other factors were associated with overall survival in the multivariate model. A multifactorial signature based on clinical and molecular baseline characteristics was capable of defining six patient clusters. Three of these clusters had significantly better prognosis, with a median overall survival of 21.3 months (95% CI 12.2 to not reached). CONCLUSIONS: High neutrophil/lymphocyte ratio at platinum-resistant relapse indicated poor prognosis in patients treated with olaparib plus pegylated liposomal doxorubicin. A multifactorial clinical signature was more precise than single variables for implying the prognosis and may help in therapeutic assignment after further validation in large prospective cohorts.

The Hibiscus Model: A Feasible Cadaveric Model Using Continuous Arterial Circulation for Intracranial Bypass Training and Its Validation.

OBJECTIVE: The frequency of intracranial bypass procedures has declined. Thus it is difficult for neurosurgeons to develop the necessary skills for this complex procedure. We present a perfusion-based cadaveric model to provide a realistic training experience with high anatomic and physiological fidelity, as well as instantaneous assessment of bypass patency. Validation was assessed by evaluating the educational impact and skill improvement of the participants. METHODS: Fourteen participants attended a hands-on revascularization course with 7 cadaveric models connected to a continuous arterial circulation system pumping a red-colored solution through the entire cranial vasculature, mimicking blood circulation. The ability to perform a vascular anastomosis was evaluated initially. Further, a questionnaire on prior experience was provided. At the end of the 36-hour course, the ability to perform an intracranial bypass was reexamined and the participants completed a self-assessment questionnaire. RESULTS: Initially, only 3 attendees were able to perform an end-to-end anastomosis within the time limit, and only 2 of these anastomoses showed adequate patency. After having accomplished the course, all participants were able to complete a patent end-to-end anastomosis within the time limit, thus demonstrating a significant improvement. Further, both overall educational gain and surgical skills were regarded as remarkable (n = 11 and n = 9). CONCLUSIONS: Simulation-based education is considered an important aspect of medical and surgical development. The presented model is a feasible and accessible alternative to the prior models used for cerebral bypass training. This training may serve as a helpful and widely available tool to improve neurosurgeons' development irrespective of financial resources.

A cross-country study on the impact of governmental responses to the COVID-19 pandemic on perinatal mental health.

This study aimed to analyse the role of governmental responses to the coronavirus disease 2019 (COVID-19) outbreak, measured by the Containment and Health Index (CHI), on symptoms of anxiety and depression during pregnancy and postpartum, while considering the countries' Inequality-adjusted Human Development Index (IHDI) and individual factors such as age, gravidity, and exposure to COVID-19. A cross-sectional study using baseline data from the Riseup-PPD-COVID-19 observational prospective international study (ClinicalTrials.gov: NCT04595123) was carried out between June and October 2020 in 12 countries (Albania, Brazil, Bulgaria, Chile, Cyprus, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom). Participants were 7645 pregnant women or mothers in the postpartum period-with an infant aged up to 6 months-who completed the Edinburgh Postnatal Depression Scale (EPDS) or the Generalised Anxiety Disorder Assessment (GAD-7) during pregnancy or the postpartum period. The overall prevalence of clinically significant depression symptoms (EPDS ≥ 13) was 30%, ranging from 20,5% in Cyprus to 44,3% in Brazil. The prevalence of clinically significant anxiety symptoms (GAD-7 ≥ 10) was 23,6% (ranging from 14,2% in Israel and Turkey to 39,5% in Brazil). Higher symptoms of anxiety or depression were observed in multigravida exposed to COVID-19 or living in countries with a higher number of deaths due to COVID-19. Furthermore, multigravida from countries with lower IHDI or CHI had higher symptoms of anxiety and depression. Perinatal mental health is context-dependent, with women from more disadvantaged countries at higher risk for poor mental health. Implementing more restrictive measures seems to be a protective factor for mental health, at least in the initial phase of the COVID-19.

Impact of the COVID-19 Pandemic on Inappropriate Use of the Emergency Department.

Background: Inappropriate use of the emergency department (IEDU)-consisting of the unnecessary use of the resource by patients with no clinical need-is one of the leading causes of the loss of efficiency of the health system. Specific contexts modify routine clinical practice and usage patterns. This study aims to analyse the influence of COVID-19 on the IEDU and its causes. Methods: A retrospective, cross-sectional study conducted in the emergency department of a high-complexity hospital. The Hospital Emergency Suitability Protocol (HESP) was used to measure the prevalence of IEDU and its causes, comparing three pairs of periods: (1) March 2019 and 2020; (2) June 2019 and 2020; and (3) September 2019 and 2020. A bivariate analysis and multivariate logistic regression models, adjusted for confounding variables, were utilized. Results: In total, 822 emergency visits were included (137 per period). A total prevalence of IEDU of 14.1% was found. There was a significant decrease in IEDU in March 2020 (OR: 0.03), with a prevalence of 0.8%. No differences were found in the other periods. A mistrust in primary care was the leading cause of IEDU (65.1%). Conclusions: The impact of COVID-19 reduced the frequency of IEDU during the period of more significant population restrictions, with IEDU returning to previous levels in subsequent months. Targeted actions in the field of population education and an improvement in primary care are positioned as strategies that could mitigate its impact.

The impact of COVID-19 on breastfeeding rates: An international cross-sectional study.

BACKGROUND: Breastfeeding promotes children's health and is associated with positive effects to maternal physical and mental health. Uncertainties regarding SARS-CoV-2 transmission led to worries experienced by women and health professionals which impacted breastfeeding plans. We aimed to investigate the impact of self-reported and country-specific factors on breastfeeding rates during the COVID-19 pandemic. METHODS: This study is part of a broader international prospective cohort study about the impact of the COVID-19 pandemic on perinatal mental health (Riseup-PPD-COVID-19). We analysed data from 5612 women, across 12 countries. Potential covariates of breastfeeding (sociodemographic, perinatal, physical/mental health, professional perinatal care, changes in healthcare due to the pandemic, COVID-19 related, breastfeeding support, governmental containment measures and countries' inequality levels) were studied by Generalized Linear Mixed-Effects Models. RESULTS: A model encompassing all covariates of interest explained 24% of the variance of breastfeeding rates across countries (first six months postpartum). Overall, first child (ß = -0.27), age of the child (ß = -0.29), preterm birth (ß = -0.52), admission to the neonatal/pediatric care (ß = -0.44), lack of breastfeeding support (ß = -0.18), current psychiatric treatment (ß = -0.69) and inequality (ß = -0.71) were negatively associated with breastfeeding (p < .001). Access to postnatal support groups was positively associated with breastfeeding (ß = 0.59; p < .001). In countries with low-inequality, governmental measures to contain virus transmission had a deleterious effect on breastfeeding (ß = -0.16; p < .05) while access to maternity leave protected breastfeeding (ß = 0.50; p < .001). DISCUSSION: This study shows that mother's COVID-19 diagnosis and changes in healthcare and birth/postnatal plans did not influence breastfeeding rates. Virtual support groups help women manage breastfeeding, particularly when their experiencing a first child and for those under psychiatric treatment. The complex associations between covariates and breastfeeding vary across countries, suggesting the need to define context-specific measures to support breastfeeding.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) DSM 19457 for all animal species for the renewal of its authorisation (Biomin GmbH).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) DSM 19457 as a technological additive for use in forage for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no evidence to lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concluded that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additive is not irritant to skin or eyes but owing to its proteinaceous nature, it should be considered a respiratory sensitiser. In the absence of data, no conclusions could be drawn on the skin sensitisation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.