Higher relative survival in breast cancer patients treated in certified and high-volume breast cancer centres - A population-based study in Belgium.

OBJECTIVES: The study was undertaken to assess the association between certification and volume of breast centres on the one hand and survival on the other in patients with invasive breast cancer (IBC). METHODS: The study comprises a cohort of 46,035 patients diagnosed with IBC between 2014 and 2018, selected from the nation-wide Belgian Cancer Registry (BCR) database, which was linked with health insurance, hospital discharge and vital status data. Overall and relative survival probabilities were obtained with Kaplan-Meier method and an actuarial approach based on Ederer II, respectively. The associations between centre certification/volume and relative survival were assessed using Poisson models, adjusted for potential confounders. RESULTS: Five years after the diagnosis of IBC, the observed and relative survival probabilities for the cohort were 83.4 % (95 %CI: [83.1, 83.8]) and 93.3 % (95 %CI: [92.9, 93.7]), respectively. After adjustment for age and combined tumour stage, the risk to die from BC was 44 % higher (EHR: 1.44, 95 %CI: [1.24, 1.66]) for patients treated in a low-volume centre and 30 % higher (EHR: 1.30, 95 %CI: [1.14, 1.48]) for patients treated in a medium-volume centre, compared to high-volume centres. Likewise, the risk to die from BC was 30 % higher (EHR: 1.30, 95 %CI: [1.15, 1.48], p < 0.001) for patients treated in a non-certified centre (representing 23.8 % of the cohort), compared to patients treated in a coordinating breast clinic. CONCLUSION: This population-based study reveals that BC survival is higher when patients are treated in certified and high-volume breast clinics.

Characterization of a Lewis adduct in its inner and outer forms.

The entrance channel of bimolecular reactions sometimes involves the formation of outer complexes as weakly bound, fleeting intermediates. Here, we characterize such an outer complex in a system that models the bimolecular, C-O bond-forming reaction of a phosphine oxide Lewis base with a carbenium Lewis acid. Crystallographic studies show that the C-O distance in the outer form exceeds that of the final or inner adduct by 1.1 angstroms. As the system samples the two forms of the complex, which correspond to minima on the corresponding potential energy surface, the C-O linkage switches from a secondary interaction in the outer complex to a dative bond in the inner complex. This phenomenon is harnessed as a functional feature to stabilize xanthylium-based photoredox catalysts.

Rh → Sb Interactions Supported by Tris(8-quinolyl)antimony Ligands.

The ligands tris(8-quinolyl)stibine and tris(6-methyl-8-quinolyl)stibine have been synthesized and complexed to rhodium using (MeCN)3RhCl3. The resulting complexes feature an unusual [RhSb]VI core as a result of the formal insertion of the antimony center into one of the Rh-Cl bonds. Computational analysis using density functional theory (DFT) methods reveals that the resulting Rh-Sb σ bond is polarized toward the Rh atom, suggesting a description of this linkage as a Rh → Sb Z-type interaction.

Differential impact of pegfilgrastim, a recombinant human granulocyte colony stimulating factor, on the neutrophil count of male and female deer mice (Peromyscus maniculatus bairdii).

BACKGROUND: An increasing body of research implicates inflammatory processes, including alterations in the neutrophil-lymphocyte ratio (NLR), in the pathophysiology of psychiatric illness. The deer mouse (Peromyscus maniculatus bairdii) is commonly studied for its naturalistic expression of compulsive-like behaviour. Towards future efforts to gain an understanding of how innate and adaptive immune processes might be involved in this model, we aimed to study the effects of pegfilgrastim, a pegylated recombinant human granulocyte colony-stimulating factor (g-CSF) analogue, on the NLR of both male and female deer mice. METHODS: Briefly, 54 deer mice (equally distributed between sexes) were exposed to a single injection with either control or pegfilgrastim (0.1 or 1 mg/kg) (n = 18 per group). Six mice of each group (three per sex) were euthanized on days two, four and seven post-administration, their blood collected and the NLR calculated. Data were analysed by means of ordinary three-way ANOVA, followed by Bonferroni post-hoc testing. RESULTS: Irrespective of dose, pegfilgrastim resulted in higher NLR values in mice of both sexes at days four and seven of testing. However, female mice exposed to the higher dose, presented with significantly higher NLR values irrespective of time, compared to male mice exposed to the same. CONCLUSION: The data generated from this work highlight important dose- and sex-specific aspects of pegfilgrastim with female mice showing heighted elevation of the NLR in response to high-dose pegfilgrastim administration only. Since the innate immune components of male and female deer mice is differentially sensitive to g-CSF stimulation, our results provide a useful basis for further study of sex-specific immunological processes in deer mice.

Passively administered fluoxetine reaches the juvenile brain of FSL rats and reduces antioxidant defences, without altering serotonin turnover.

BACKGROUND: Fluoxetine is present in breast milk, yet it is unclear to what extent it, or its active metabolite, norfluoxetine, reaches the brain of the infant and what the effects of such exposure on neurobiological processes are. We therefore aimed to quantify the concentration of passively administered fluoxetine and norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) offspring and establish their influence on serotonergic function and redox status. METHODS: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04. Offspring were passively exposed to fluoxetine until postnatal day 18 and euthanized on postnatal day 22. Whole brain fluoxetine, norfluoxetine, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and reduced (GSH) and oxidized glutathione (GSSG) concentrations were measured via liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: Whole-brain serotonin and 5-hydroxyindoleacetic acid concentrations, and serotonin turnover (5-HIAA/5-HT) were comparable between strains. Treatment-naïve FSL rats had lower GSH and higher GSSG whole-brain concentrations, relative to FRL controls, and an overall decreased GSH/GSSG ratio. Passively administered fluoxetine resulted in undetectable whole-brain concentrations, while norfluoxetine averaged 41.28 ± 6.47 ng/g. Serotonin turnover of FSL rats was unaffected by passively administered fluoxetine, while redox status (GSH/GSSG) was decreased. CONCLUSION: Our findings confirm that passively administered fluoxetine reaches the infant brain in the form of norfluoxetine and may manipulate processes of oxidative stress regulation. Further studies into the long-term bio-behavioural effects are however needed to effectively inform breast feeding mothers on the safety of antidepressant-use.

Temporal Dynamics of Plasma Catecholamines, Metabolic and Immune Markers, and the Corticosterone:DHEA Ratio in Farmed Crocodiles before and after an Acute Stressor.

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone (CORT), dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to the baseline. Downstream effects of these catecholamines and CORT appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to the baseline by the final measurement. DHEA, which is used in a ratio with CORT, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to our understanding of crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

Flexural Properties, Wear Resistance, and Microstructural Analysis of Highly Filled Flowable Resin Composites.

OBJECTIVE: This study aimed to evaluate the flexural properties and two-body wear resistance of nine highly filled flowable resin composites relative to those of viscous and conventional low-filled flowable composites. In addition, scanning electron microscopy (SEM) analysis of the microstructures was performed. METHODS AND MATERIALS: For each resin composite group (n=12), 12 specimen bars (25 mm × 2 mm × 2 mm) were fabricated using a silicon mold for performing flexural strength (FS), flexural modulus (E), flexural toughness (FT), Weibull modulus (m) tests, and SEM microstructural analysis. For each group, ten bars were tested using a three-point flexural test on a universal testing machine, while the other two were embedded in acrylic resin before being observed by SEM for structural analysis. During the two-body wear test with a chewing simulator, 8 specimens (12 groups, n=8) of each resin composite group were manufactured in a specific mold and subjected to 120,000 cycles of wear against a steatite ball, and the depth loss was measured. Three one-way ANOVA tests followed by Tukey's post hoc tests were conducted to compare the flexural and wear properties among the different groups. RESULTS: The majority of highly filled composites tested in this study exhibited similar flexural strengths (between 105.68 MPa and 135.49 MPa) and superior wear resistance to those of viscous composites. The flexural moduli (between 5.12 GPa and 9.62 GPa) of these composites were in between those of the viscous and low-filled composites tested in this study. CONCLUSIONS: The highly filled flowable composites tested in this study exhibited different in vitro properties but were often superior to those of viscous resin composite suggesting their possible use for posterior restorations.

Exploring the Effects of Se Basicity on a Te···Se Interaction Supported by a Rigid Indazolium Backbone.

With an interest in chalcogen bonding, we use a rigid indazolium backbone to install a formally zero-valent Se center next to a divalent Te center, allowing us to investigate the effects of oxidation of the Se center on the observed Te···Se interaction. Through spectroscopic and computational comparison of the Se(0) species with its Se(II) counterpart and their monochalcogen analogues, we experimentally and computationally investigate the effect of modulating Se basicity on the resulting Te···Se interaction. Comparison with well-studied naphthalene and acenaphthene variants indicates that the increased basicity of the Se(0) center allows for a comparably strong Te···Se interaction despite longer peri distances and a larger splay angle. Finally, our study illuminates the potential non-innocence of cationic organic substituents in chalcogen-bonding catalysis of the transfer hydrogenation of quinolines.

Plant interactions can lead to emergent relationships between plant community diversity, productivity and vulnerability to invasion.

Understanding what makes a community vulnerable to invasion is integral to the successful management of invasive species. Our understanding of how characteristics of resident plant interactions, such as the network architecture of interactions, can affect the invasibility of plant communities is limited. Using a simulation model, we tested how successfully a new plant invader established in communities with different network architectures of species interactions. We also investigated whether species interaction networks lead to relationships between invasibility and other community properties also affected by species interaction networks, such as diversity, species dominance, compositional stability and the productivity of the resident community. We found that higher invasibility strongly related with a lower productivity of the resident community. Plant interaction networks influenced diversity and invasibility in ways that led to complex but clear relationships between the two. Heterospecific interactions that increased diversity tended to decrease invasibility. Negative conspecific interactions always increased diversity and invasibility, but increased invasibility more when they increased diversity less. This study provides new theoretical insights into the effects of plant interaction networks on community invasibility and relationships between diversity and invasibility. Combined with increasing empirical evidence, these insights could have useful implications for the management of invasive plant species.

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: In DESTINY-Breast02, patients with HER2-positive unresectable or metastatic breast cancer who received trastuzumab deruxtecan demonstrated superior progression-free and overall survival compared with those receiving treatment of physician's choice. We present the patient-reported outcomes (PROs) and hospitalisation data. METHODS: In this randomised, open-label, phase 3 trial conducted at 227 clinical sites globally, enrolled patients had to be aged 18 years or older with HER2-positive unresectable or metastatic breast cancer that had progressed on trastuzumab emtansine and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using block randomisation (block size of 3) to receive trastuzumab deruxtecan (5·4 mg/kg intravenously once every 21 days) or treatment of physician's choice by an independent biostatistician using an interactive web-based system. Patients and investigators remained unmasked to treatment. Treatment of physician's choice was either capecitabine (1250 mg/m2 orally twice per day on days 1-14) plus trastuzumab (8 mg/kg intravenously on day 1 then 6 mg/kg once per day) or capecitabine (1000 mg/m2) plus lapatinib (1250 mg orally once per day on days 1-21), with a 21-day schedule. The primary endpoint, which was progression-free survival based on blinded independent central review, has previously been reported. PROs were assessed in the full analysis set (all patients randomly assigned to the study) using the oncology-specific European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), breast cancer-specific EORTC Quality of Life Questionnaire Breast 45 (QLQ-BR45), and the generic HRQoL EQ-5D-5L questionnaire. Analyses included change from baseline and time to definitive deterioration for PRO variables of interest and hospitalisation-related endpoints. This study is registered with ClinicalTrials.gov, NCT03523585, and is closed to recruitment. FINDINGS: Between Sept 6, 2018, and Dec 31, 2020, 608 patients were randomly assigned to receive either trastuzumab deruxtecan (n=406; two did not receive treatment) or treatment of physician's choice (n=202; seven did not receive treatment). Overall, 603 patients (99%) were female and five (<1%) were male. The median follow-up was 21·5 months (IQR 15·2-28·4) in the trastuzumab deruxtecan group and 18·6 months (IQR 8·8-26·0) in the treatment of physician's choice group. Median treatment duration was 11·3 months (IQR 6·2-20·5) in the trastuzumab deruxtecan group and approximately 4·5 months in the treatment of physician's choice group (4·4 months [IQR 2·5-8·7] with trastuzumab; 4·6 months [2·1-8·9] with capecitabine; and 4·5 months [2·1-10·6] with lapatinib). Baseline EORTC QLQ-C30 global health status (GHS) scores were similar with trastuzumab deruxtecan (n=393) and treatment of physician's choice (n=187), and remained stable with no clinically meaningful change (defined as ≥10-point change from baseline) over time. Median time to definitive deterioration was delayed with trastuzumab deruxtecan compared with treatment of physician's choice for the primary PRO variable EORTC QLQ-C30 GHS (14·1 months [95% CI 10·4-18·7] vs 5·9 months [4·3-7·9]; HR 0·5573 [0·4376-0·7099], p<0·0001) and all other prespecified PROs (EORTC QLQ-C30 subscales, EORTC QLQ-BR45 arm and breast symptoms, and EQ-5D-5L visual analogue scale). Patient hospitalisation rates were similar in the trastuzumab deruxtecan (92 [23%] of 406) and treatment of physician's choice (41 [20%] of 202) groups; however, median time to hospitalisation was 133 days (IQR 56-237) with trastuzumab deruxtecan versus 83 days (30-152) with treatment of physician's choice. INTERPRETATION: Overall, GHS and quality of life were maintained for both treatment groups, with prespecified PRO variables favouring trastuzumab deruxtecan over treatment of physician's choice, suggesting that despite a longer treatment duration, there was no detrimental impact on patient health-related quality of life with trastuzumab deruxtecan. When considered with efficacy and safety data from DESTINY-Breast02, these results support the overall benefit of trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine. FUNDING: Daiichi Sankyo and AstraZeneca.

Study design for DESTINY-Breast Respond HER2-low Europe: T-DXd in patients with HER2-low advanced breast cancer.

Trastuzumab deruxtecan (T-DXd) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). Results on T-DXd treatment in HER2-low mBC have so far been limited to clinical trials. DESTINY-Breast Respond HER2-low Europe (NCT05945732) is a multi-center, multi-country, observational, prospective, non-interventional study planning to enroll 1350 patients from 216 sites receiving T-DXd or conventional chemotherapy as their routine clinical care for advanced stage breast cancer in 12 European countries. This non-interventional study will provide real-world insight into T-DXd treatment for HER2-low mBC with data on effectiveness, safety and tolerability, patient-reported outcomes, treatment patterns, geriatric health status and HER2 testing. This will be beneficial for improving guidance to maximize patient treatment benefit.

Trastuzumab deruxtecan (T-DXd; Enhertu^®) is a medicine approved to treat cancers that produce a protein called HER2 on the surface of cancer cells. T-DXd works by targeting the HER2 protein to deliver chemotherapy directly to cancer cells. Until recently, breast cancers were classified as HER2-positive (high level of HER2 protein on cancer cells) or HER2-negative (very low level/no HER2 protein on cancer cells). T-DXd was approved for treating patients with HER2-positive advanced breast cancer in Europe in 2022. In 2023 the DESTINY-Breast04 clinical trial showed that T-DXd was more effective than current standard chemotherapies, when treating advanced breast cancer patients with low levels of the HER2 protein (historically classified as HER2-negative cancer). This trial led to the approval of T-DXd for treating advanced HER2-low breast cancer, providing a new treatment option for 50­60% of breast cancer patients. More information is needed about T-DXd treatment in the real world (for patients treated in the hospital, rather than in a clinical trial). This article describes the purpose and design of the DESTINY-Breast Respond HER2-low Europe study, which will collect and report more information about how effective T-DXd treatment is in the real world. This is a large study aiming to include 1350 eligible patients from 12 countries across Europe. Patients will report their experience of side effects (such as nausea and vomiting) to improve management of T-DXd treatment and maximize patient benefit. The study will also examine how elderly patients respond to T-DXd treatment, and how HER2 levels are being tested.Clinical Trial Registration: ICH CGP: NCT05945732, registered on 6 July 2023 (ClinicalTrials.gov).

Case report: Aberrant fecal microbiota composition of an infant diagnosed with prolonged intestinal botulism.

BACKGROUND: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. CASE PRESENTATION: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. CONCLUSION: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

Tunable Pnictogen Bonding at the Service of Hydroxide Transport across Phospholipid Bilayers.

Our growing interest in the design of pnictogen-based strategies for anion transport has prompted an investigation into the properties of three simple triarylcatecholatostiboranes (1-3) of the general formula (o-C6Cl4O2)SbAr3 with Ar = Ph (1), o-tolyl (2), and o-xylyl (3) for the complexation and transport of hydroxide across phospholipid bilayers. A modified hydroxypyrene-1,3,6-trisulfonic acid (HPTS) assay carried out in artificial liposomes shows that 1 and 2 are potent hydroxide transporters while 3 is inactive. These results indicate that the steric hindrance imposed by the three o-xylyl groups prevents access by the hydroxide anion to the antimony center. Supporting this interpretation, 1 and 2 quickly react with TBAOH·30 H2O ([TBA]+ = [nBu4N]+) to form the corresponding hydroxoantimonate salts [nBu4N][1-OH] and [nBu4N][2-OH], whereas 3 resists hydroxide coordination and remains unperturbed. Moreover, the hydroxide transport activities of 1 and 2 are correlated to the +V oxidation state of the antimony atom as the parent trivalent stibines show no hydroxide transport activity.

Dehorning Does Not Alter the Stress Response in Southern White Rhinoceroses (Ceratotherium simum simum) during Transport: A Preliminary Investigation.

Translocation and dehorning are common and important practices for rhinoceros management and conservation. It is not known if dehorning causes a stress response or negatively affects rhinoceroses during transport. Twenty-three subadult wild Southern white rhinoceros (Ceratotherium simum simum) bulls were immobilized and translocated >280 km for population management reasons. Ten animals were dehorned at capture, and 13 animals were transported without dehorning. For transport, five dehorned and six nondehorned rhinoceroses were sedated with azaperone (62.38±9.54 µg/kg) and five dehorned and seven nondehorned rhinoceroses with midazolam (64.61±9.28 µg/kg). Blood samples were collected at capture, start of transport, and after 6 h of transport. Measurements included 10 physiologic variables: hematocrit, total serum protein, creatine kinase (CK), aspartate aminotransferase, gamma-glutamyl transferase (GGT), creatinine, urea, cholesterol, ß-hydroxybutyrate, and glucose; and four stress response variables: cortisol, epinephrine, neutrophil-to-lymphocyte ratio, and leukocyte coping capacity. Using a linear mixed model, CK and GGT were higher in dehorned compared with nondehorned rhinoceroses. There were no significant differences in the other variables between the two groups. The likely cause of these differences is that dehorned animals spent more time in the crate before the start of transport than nondehorned rhinoceroses (3:11±0:54 h vs. 1:12±0:56 h, P<0.001). These results indicate that dehorning does not negatively alter the white rhinoceros' physiologic and stress responses during translocation, supporting its use for antipoaching measures.

Metabolic adaptation towards glycolysis supports resistance to neoadjuvant chemotherapy in early triple negative breast cancers.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard of care for patients with early-stage triple negative breast cancers (TNBC). However, more than half of TNBC patients do not achieve a pathological complete response (pCR) after NAC, and residual cancer burden (RCB) is associated with dismal long-term prognosis. Understanding the mechanisms underlying differential treatment outcomes is therefore critical to limit RCB and improve NAC efficiency. METHODS: Human TNBC cell lines and patient-derived organoids were used in combination with real-time metabolic assays to evaluate the effect of NAC (paclitaxel and epirubicin) on tumor cell metabolism, in particular glycolysis. Diagnostic biopsies (pre-NAC) from patients with early TNBC were analyzed by bulk RNA-sequencing to evaluate the predictive value of a glycolysis-related gene signature. RESULTS: Paclitaxel induced a consistent metabolic switch to glycolysis, correlated with a reduced mitochondrial oxidative metabolism, in TNBC cells. In pre-NAC diagnostic biopsies from TNBC patients, glycolysis was found to be upregulated in non-responders. Furthermore, glycolysis inhibition greatly improved response to NAC in TNBC organoid models. CONCLUSIONS: Our study pinpoints a metabolic adaptation to glycolysis as a mechanism driving resistance to NAC in TNBC. Our data pave the way for the use of glycolysis-related genes as predictive biomarkers for NAC response, as well as the development of inhibitors to overcome this glycolysis-driven resistance to NAC in human TNBC patients.

An interactive atlas of three-dimensional syndromic facial morphology.

Craniofacial phenotyping is critical for both syndrome delineation and diagnosis because craniofacial abnormalities occur in 30% of characterized genetic syndromes. Clinical reports, textbooks, and available software tools typically provide two-dimensional, static images and illustrations of the characteristic phenotypes of genetic syndromes. In this work, we provide an interactive web application that provides three-dimensional, dynamic visualizations for the characteristic craniofacial effects of 95 syndromes. Users can visualize syndrome facial appearance estimates quantified from data and easily compare craniofacial phenotypes of different syndromes. Our application also provides a map of morphological similarity between a target syndrome and other syndromes. Finally, users can upload 3D facial scans of individuals and compare them to our syndrome atlas estimates. In summary, we provide an interactive reference for the craniofacial phenotypes of syndromes that allows for precise, individual-specific comparisons of dysmorphology.

Antiseizure medication ≤48 hours portends better prognosis in new-onset epilepsy.

BACKGROUND: Several studies found that patients with new-onset epilepsy (NOE) have higher seizure recurrence rates if they presented already prior seizures. These observations suggest that timing of antiseizure medication (ASM) is crucial and should be offered immediately after the first seizure. Here, we wanted to assess whether immediate ASM is associated with improved outcome. METHODS: Single-center study of 1010 patients (≥16 years) who presented with a possible first seizure in the emergency department between 1 March 2010 and 1 March 2017. A comprehensive workup was launched upon arrival, including routine electroencephalography (EEG), brain computed tomography/magnetic resonance imaging, long-term overnight EEG and specialized consultations. We followed patients for 5 years comparing the relapse rate in patients treated within 48 h to those with treatment >48 h. RESULTS: A total of 487 patients were diagnosed with NOE. Of the 416 patients (162 female, age: 54.6 ± 21.1 years) for whom the treatment start could be retrieved, 80% (333/416) were treated within 48 h. The recurrence rate after immediate treatment (32%; 107/333) was significantly lower than in patients treated later (56.6%; 47/83; p < 0.001). For patients for whom a complete 5-year-follow-up was available (N = 297, 123 female), those treated ≤48 h (N = 228; 76.8%) had a significantly higher chance of remaining seizure-free compared with patients treated later (N = 69; 23.2%; p < 0.001). CONCLUSIONS: In this retrospective study, immediate ASM therapy (i.e., within 48 h) was associated with better prognosis up to 5 years after the index event. Prospective studies are required to determine the value of immediate workup and drug therapy in NOE patients.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

PURPOSE: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer. METHODS: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases. "Surgery" group was defined by surgery of primary tumor up to nine months after diagnosis. We excluded women who did not receive systemic treatment or did not complete nine months follow-up after diagnosis. All the subsequent analyses reporting on overall survival and the stratified outcome analyses were performed based on this nine-month landmark cohort. OS was estimated using Kaplan-Meier method and compared using adjusted Cox proportional hazards models controlling for confounders with 95% confidence intervals (CI). We performed a stratified analysis according to surgery timing and a propensity score matching analysis. RESULTS: 1985 patients, 534 (26.9%) in the "Surgery" and 1451 (73.1%) in the "No Surgery" group. Patients undergoing surgery were younger (p < 0.001), had better performance status (PS) (p < 0.001), and higher proportion of HER2-positive and triple-negative breast cancer (p = 0.012). Median follow-up was 86.0 months (82.6-88.5). Median OS was 60.1 months (57.1-68.2) in the "Surgery" vs. 41.9 months (39.8-44.2) in the "No Surgery" group (adjusted HR 0.56; 0.49-0.64). OS was similar when surgery was performed upfront or after systemic treatment. Propensity score matching analysis confirmed the same findings. CONCLUSION: Among patients receiving systemic treatment for de novo metastatic breast cancer and surviving nine months or more, those who received surgery of the primary tumor within nine months of diagnosis have longer subsequent survival than those who did not.