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Purpose: Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10–89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life. Methods: The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years. Conclusion: This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST. Trial registration: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).

BACKGROUND: Idiopathic ventricular fibrillation (iVF) is a diagnosis of exclusion. Systematic diagnostic testing is important to exclude alternative causes for VF. The early use of "high yield" testing, including cardiac magnetic resonance (CMR), exercise testing, and sodium channel blocker provocation, has been increasingly recognized. OBJECTIVES: The purpose of this study was to investigate the importance and consistency of systematic diagnostic testing in iVF. METHODS: This study included 423 iVF patients from 11 large secondary and tertiary hospitals in the Netherlands. Clinical characteristics and diagnostic testing data were ascertained. RESULTS: IVF patients experienced the index event at a median age of 40 years (IQR: 28-52 years), and 61% were men. The median follow-up time was 6 years (IQR: 2-12 years). Over the years, "high yield" diagnostic tests were increasingly performed (mean 68% in 2000-2010 vs 75% in 2011-2021; P < 0.001). During follow-up, 38 patients (9%) originally labeled as iVF received an alternative diagnosis. Patients in whom "high-yield" diagnostic tests were consistently performed during the initial work-up received an alternative diagnosis less frequently during follow-up (HR: 0.439; 95% CI: 0.219-0.878; P = 0.020). Patients who received an alternative diagnosis during follow-up had a worse prognosis in terms of cardiac death (P = 0.012) with a trend toward more implantable cardioverter-defibrillator therapy (P = 0.055). CONCLUSIONS: Although adherence to (near) complete diagnostic testing in this population of iVF patients increased over the years, patients with iVF still undergo varying levels of diagnostic evaluation. The latter leads to initial underdiagnosis of alternative conditions and is associated with a worse prognosis. Our results underscore the importance of early systematic diagnostic assessment in patients with apparent iVF.

BACKGROUND: Idiopathic ventricular fibrillation (iVF) is a diagnosis of exclusion. Systematic diagnostic testing is important to exclude alternative causes for VF. The early use of "high yield" testing, including cardiac magnetic resonance (CMR), exercise testing, and sodium channel blocker provocation, has been increasingly recognized.OBJECTIVES: The purpose of this study was to investigate the importance and consistency of systematic diagnostic testing in iVF.METHODS: This study included 423 iVF patients from 11 large secondary and tertiary hospitals in the Netherlands. Clinical characteristics and diagnostic testing data were ascertained.RESULTS: IVF patients experienced the index event at a median age of 40 years (IQR: 28-52 years), and 61% were men. The median follow-up time was 6 years (IQR: 2-12 years). Over the years, "high yield" diagnostic tests were increasingly performed (mean 68% in 2000-2010 vs 75% in 2011-2021; P < 0.001). During follow-up, 38 patients (9%) originally labeled as iVF received an alternative diagnosis. Patients in whom "high-yield" diagnostic tests were consistently performed during the initial work-up received an alternative diagnosis less frequently during follow-up (HR: 0.439; 95% CI: 0.219-0.878; P = 0.020). Patients who received an alternative diagnosis during follow-up had a worse prognosis in terms of cardiac death (P = 0.012) with a trend toward more implantable cardioverter-defibrillator therapy (P = 0.055).CONCLUSIONS: Although adherence to (near) complete diagnostic testing in this population of iVF patients increased over the years, patients with iVF still undergo varying levels of diagnostic evaluation. The latter leads to initial underdiagnosis of alternative conditions and is associated with a worse prognosis. Our results underscore the importance of early systematic diagnostic assessment in patients with apparent iVF.

ObjectiveRetrospective series have shown minimally invasive secondary cytoreductive surgery is a feasible approach in selected cases of recurrent ovarian cancer. However, no predictors of minimally invasive secondary cytoreductive surgery feasibility are currently available. This study aims to identify predictive factors of minimally invasive secondary cytoreductive surgery feasibility and to compare perioperative and survival outcomes in a matched series of recurrent ovarian cancer patients who underwent secondary cytoreduction via an open or minimally invasive surgical approach.MethodsWe retrospectively identified all platinum-sensitive recurrent epithelial ovarian cancer patients who underwent minimally invasive or laparotomic secondary cytoreductive surgery between January 2013 and July 2020. Each patient underwent a preoperative positron emission tomography (PET) computerized tomography (CT) scan and diagnostic laparoscopy before secondary cytoreductive surgery. A 1:2 propensity score-matched analysis was performed to balance predictive factors of minimally invasive secondary cytoreductive surgery.ResultsOverall, 276 patients were identified (62 minimally invasive and 214 open), and a complete gross resection was achieved in 262 (94.9%) patients. At multivariate analysis, predictive factors for minimally invasive secondary cytoreductive surgery were neoadjuvant chemotherapy at first diagnosis (p=0.007), site of recurrence (p=0.031), and number of lesions (p=0.001). In the 1:2 propensity-matched population (39 minimally invasive and 78 open), complete gross resection was similar for both groups (p=0.082). Early post-operative complications were significantly higher in the laparotomy (33.3%) than in the minimally invasive surgery (10.3%) group (p=0.004). Only one (2.6%) patient experienced a grade >3 early post-operative complication in the minimally invasive surgery group compared with 13 (16.7%) patients in the open cohort (pConclusionsPatients with single or oligometastatic recurrences can be offered minimally invasive secondary cytoreductive surgery, mainly if localized in the lymph-nodes, and/or if they received neoadjuvant chemotherapy at primary diagnosis. Minimally invasive secondary cytoreductive surgery is associated with favorable perioperative outcomes with no differences in terms of post-recurrence survival with respect to open approach.

ObjectiveThe primary endpoint of this study was to compare the disease-free survival of patients undergoing open versus minimally invasive pelvic exenteration. The secondary endpoints were cancer-specific survival and peri-operative morbidity.MethodsA multi-center, retrospective, observational cohort study was undertaken. Patients undergoing curative and palliative anterior or total pelvic exenteration for gynecological cancer by a minimally invasive approach and an open approach between June 2010 and May 2021 were included. Patients with distant metastases were excluded. A 1:2 propensity match analysis between patients undergoing minimally invasive and open pelvic exenteration was performed to equalized baseline characteristics.ResultsAfter propensity match analysis a total of 117 patients were included, 78 (66.7%) and 39 (33.3%) in the open and minimally invasive group, respectively. No significant difference in intra-operative (23.4% vs 10.3%, p=0.13) and major post-operative complications (24.4% vs 17.9%, p=0.49) was evident between the open and minimally invasive approach. Patients undergoing open pelvic exenteration received higher rates of intra-operative transfusions (41.0% vs 17.9%, p=0.013). Median disease-free survival was 17.0 months for both the open and minimally invasive groups (p=0.63). Median cancer-specific survival was 30.0 months and 26.0 months in the open and minimally invasive groups, respectively (p=0.80). Positivity of surgical margins at final histology was the only significant factor influencing the risk of recurrence (hazard ratio (HR) 2.38, 95% CI 1.31 to 4.31) (p=0.004), while tumor diameter ≥50 mm at the time of pelvic exenteration was the only significant factor influencing the risk of death (HR 1.83, 95% CI 1.08 to 3.11) (p=0.025).ConclusionIn this retrospective study no survival difference was evident when minimally invasive pelvic exenteration was compared with open pelvic exenteration in patients with gynecological cancer. There was no difference in peri-operative complications, but a higher intra-operative transfusion rate was seen in the open group.

Objectives: We investigated AB0 blood groups prevalence according to preoperative and pathological tumor characteristics, and their association with oncological outcomes, and renal function decline in a contemporary large cohort of bladder cancer (BCa) patients, who underwent radical cystectomy (RC) at a tertiary referral center. Materials and Methods: We retrospectively evaluated data of patients with histologically confirmed and clinically non metastatic BCa, who underwent RC between 2014 and 2021 at our Institution. Kaplan-Meier (KM) plots and Cox regression (CR) models tested the relationship between AB0 blood groups and local recurrence-, metastasis-, cancer specific mortality-, and overall mortality-free survival. Logistic regression (LR) models tested the association between AB0 blood groups and renal function decline, defined as an estimated Glomerular Filtration Rate (eGFR) < 60 mL/min, at post-operative day 1, discharge and 6- months of follow-up. Results: Of 301 included patients, 128 (42.5%) had group A, 126 (41.9%) had group 0, 28 (9.3%) had group B, and 19 (6.3%) had group AB. Patients with group 0 developed higher rates of muscle- invasive BCa (p = 0.028) with high-grade features (p = 0.005) at last bladder resection, and less frequently received preoperative immunotherapy with Bacillus of Calmette-Guerin (p = 0.044), than their non-0 counterparts. Additionally, these patients harbored more advanced pathologic tumor stage at RC (p = 0.024). KM plots showed no differences among all tested cancer control outcomes between AB0 blood groups (p > 0.05 in all cases). Patients with group AB presented the lowest median eGFR at each time point. In multivariable LR analyses addressing renal function decline, group AB was independently associated with eGFR< 60 mL/min at discharge (Odds Ratio: 4.28, p = 0.047). Conclusions: Among AB0 blood groups, patients with group 0 exhibited the most aggressive tumor profile. However, no differences were recorded in recurrence or survival rates. Group AB independently predicted renal function decline at discharge.

ObjectivePoly (ADP-ribose) polymerase (PARP) inhibitor resistance is problematic in epithelial ovarian cancer management and sequencing strategies may be performed to overcome this issue. In this context, our study evaluated the role of non-platinum doublet pegylated liposomal doxorubicin/trabectedin in ovarian cancer platinum-sensitive patients who experienced disease progression under PARP inhibitor maintenance.MethodsThis case–control study includes patients with recurrent epithelial ovarian cancer treated between March 2016 and April 2021 who progressed under PARP inhibitor maintenance. Data of patients treated with pegylated liposomal doxorubicin/trabectedin (experimental group) were matched 1:1 with a series of patients who received platinum-based treatment (control group). The study outcomes were overall clinical benefit (including complete, partial, and stable response), progression-free survival, and overall survival. The safety of both treatments was also evaluated.ResultsA total of 26 patients in both groups were analyzed. Clinical benefit was achieved in 15 (57%) patients in the study group and 17 (65%) patients in the control group (p=0.38). Patients receiving pegylated liposomal doxorubicin/trabectedin had 5 months of progression-free survival, compared with 5 months in patients treated with platinum-based treatment (p=0.62). Patients in the experimental group achieved a median overall survival of 16 months compared with 19 months in the control group (p=0.26) There was no difference concerning severe toxicities (G3-G4) between groups, except for hepatic toxicity, which was experienced in 30% of the patients receiving pegylated liposomal doxorubicin/trabectedin and none in the control group (pConclusionsPegylated liposomal doxorubicin/trabectedin might be an alternative option to platinum-based treatment in patients experiencing disease progression during PARP inhibitor maintenance with an acceptable toxicity profile. This might be a therapeutic option in this setting, sparing platinum compounds for subsequent relapse.

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro. We utilized time-course resolved RNA-sequencing to globally profile transcriptome changes as SCLC cells responded to a combination of cisplatin and etoposide—the standard-of-care in SCLC. Comparisons across time points demonstrated a distinct transient transcriptional state resembling embryonic diapause. Differential gene expression analysis revealed that expression of the PEA3 transcription factors ETV4 and ETV5 were transiently upregulated in the surviving fraction of cells which we determined to be necessary for efficient clonogenic expansion following chemotherapy. The FGFR-PEA3 signaling axis guided the identification of a pan-FGFR inhibitor demonstrating in vitro and in vivo efficacy in delaying progression following combination chemotherapy, observed inhibition of phosphorylation of the FGFR adaptor FRS2 and corresponding downstream MAPK and PI3K-Akt signaling pathways. Taken together, these data nominate PEA3 transcription factors as key mediators of relapse progression in SCLC and identify a clinically actionable small molecule candidate for delaying relapse of SCLC.

IntroductionHyaluronan (HA) accumulation is associated with tumorigenesis and aggressive tumor behavior.AimsWe investigated the biomarker potential of HA in non-small cell lung cancer (NSCLC).MethodsHA levels were scored using affinity histochemistry in 137 NSCLC samples stratified by HA score ≤10, 11-20, 21-30, and >30 with HA-high defined as ≥25% expression in the extracellular matrix (ECM) of the tumor surface area. Overall survival (OS) and time to progression from initiation of taxane therapy (TTP) were compared using log-rank tests based on HA score.ResultsOf 122 patients with recurrent/metastatic NSCLC, 93 had mean HA scores that were not significantly different across clinicopathologic variables. Frequency of HA-high tumors did not differ by histology (34/68 adenocarcinomas vs. 12/25 squamous tumors, Fisher's p = 1.0000). Median OS for recurrent/metastatic adenocarcinoma was 35.5 months (95%, 23.6-50.3) vs. 17.9 months for squamous (95%, 12.7-37.0, log-rank test, p = 0.0165). OS was not significantly different by HA quartiles, high or low ( 0.05). Median TTP (n = 98) significantly differed by HA quartile (2.8 months for HA score ≤10; 5.0 months for 11-20; 7.9 months for 21-30; 3.9 months for >30, p = 0.0265). Improved TTP trended in HA-high over HA-low tumors (n = 98, p = 0.0911).ConclusionIn this NSCLC cohort, tumor HA level represents a potential biomarker for TTP, which remains a cornerstone of NSCLC therapy. Further validation is warranted to identify the HA accumulation threshold associated with clinical benefit.

PURPOSE ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735 ) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study. METHODS Patients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest safe dose permitted) followed by initiation of dose expansion. RESULTS As of January 8, 2022, 124 patients (dose escalation [0.025-120 mg], n = 73; dose expansion [60 mg], n = 51) have received ABBV-383; median age was 68 years (range, 35-92 years). The most common hematologic treatment-emergent adverse events (TEAEs) were neutropenia (all grades: 37%) and anemia (29%). The most common nonhematologic TEAEs were cytokine release syndrome (57%) and fatigue (30%). Seven deaths from TEAEs were reported with all considered unrelated to study drug by the investigator. For all efficacy-evaluable patients (n = 122; all doses), the objective response rate (ORR) was 57% and very good partial response (VGPR) or better (≥ VGPR) rate was 43%. In the 60 mg dose expansion cohort (n = 49), the ORR and ≥ VGPR rates were 59% and 39%, respectively; and in the ≥ 40 mg dose escalation plus dose expansion cohorts (n = 79) were 68% and 54%, respectively. CONCLUSION ABBV-383 in patients with RRMM was well tolerated with an ORR of 68% at doses ≥ 40 mg. This novel therapy's promising preliminary antitumor activity in heavily pretreated patients warrants further clinical evaluation.

Multispecies ethnography attempts to bring to the forefront those animal lives previously overlooked by charting our shared social worlds and showing how humans and nonhumans are mutually affected by social, cultural and political processes. The resistance in postcolonial critique to focus on nonhuman animal subjects stems from making the colonised and the animal comparable and the fear that such an association may dehumanise the human subject. This paper suggests that multispecies ethnography influenced by Latour, Haraway, Tsing and others is a useful tool for analysing postcolonial contexts because of its emphasis on relation, mutuality and alliances. However, I suggest that this inheritance is rebuilt as a postcolonial multispecies ethnography because of its attention to five aspects that is common to both fields: subaltern, local, collective, representation and decolonisation. By a careful reading of these key concepts with examples from contemporary literature, I show how "postcolonial" multispecies ethnographies engage with hybrid identities that are culturally produced and historically situated and how they register the nonhuman animals as narrativisable subjects who are nevertheless “irretrievably heterogeneous” (284). In this ethnographic emergence, postcolonial multispecies ethnography re-dignifies the nonhuman animal subject which opens up the radical possibility of realizing their embodied perspectives., La etnografía multiespecie intenta poner en primera fila las vidas de aquellos animales que anteriormente se han ignorado trazando los mundos sociales compartidos y mostrando cómo humanos y no humanos se ven mutuamente afectados por los procesos sociales, culturales y políticos. La resistencia de la crítica poscolonial a la hora de fijarse en los sujetos animales no humanos surge de que la comparación del colonizado y el animal pueda deshumanizar al sujeto humano. Este ensayo sugiere que la etnografía multiespecie influida por Latour, Haraway, Tsing y otros es una herramienta útil para analizar los contextos poscoloniales debido a su énfasis en la relación, la mutualidad y las alianzas. Sin embargo, sugiero que este legado se reconstruye como una etnografía multiespecie "poscolonial" en base a su atención a cinco aspectos comunes a ambos campos: lo subalterno, lo local, lo colectivo, la representación y la descolonización. Por medio de una lectura detallada de estos conceptos clave con ejemplos de la literatura contemporánea, muestro como las etnografías multiespecie poscoloniales interactúan con las identidades híbridas producidas culturalmente y situadas históricamente, y cómo registran a los animales no humanos como sujetos narrativizables que son, no obstante, “irremediablemente heterogéneos” (284). En este afloramiento etnográfico, la etnografía multiespecie poscolonial re-dignifica al sujeto animal no-humano que se abre a la posibilidad radical de hacer realidad sus perspectivas encarnadas.

El objetivo del presente estudio fue comparar el efecto de la electroquimioterapia (EQT) más bleomicina local y sistémica, en perros con neoplasias de diferentes orígenes celulares, los cuales fueron atendidos en la Clínica Veterinaria “La Primavera” de la ciudad de Quito, Pichincha, Ecuador, para lo cual se contó con 10 pacientes caninos (Canis lupus familiaris). El diagnostico se realizó mediante histopatología y citología, el cálculo volumétrico del tumor se obtuvo mediante la fórmula para calcular el volumen tumoral [(a×b×c×(π/6)]. El tratamiento se basó en la administración de bleomicina 15 unidades internacionales por metro cuadrado (UI·m2) de superficie corporal, vía sistémica, e infiltración intratumoral de bleomicina a la dosis de 0,25 UI por centimetro cúbico (UI·cm3) de superficie tumoral, considerando la alta selectividad de la bleomicina por las células epiteliales y las características de vascularización tumoral, de forma posterior se aplicaron pulsos eléctricos con una intensidad de 1.000 voltios por centimetro cuadrado (V·cm2), utilizando diferentes tipos de electrodos. Veintiocho días (d) posteriores a la aplicación de la terapia se logró reducir en un 50 % las masas tumorales, logrando una respuesta objetiva al tratamiento aplicado. The objective of the present study was to compare the effect of electrochemotherapy (ECT) plus local and systemic bleomycin, in dogs with neoplasms of different cellular origins, which were treated at the “La Primavera” Veterinary Clinic in the City of Quito, Pichincha, Ecuador. There were 10 canine patients (Canis lupus familiaris). The diagnosis was made by histopathology and cytology, the volumetric calculation of the tumor was obtained using the formula to calculate the tumor volume [(a×b×c×(π/6)]. The treatment was based on the administration of bleomycin 15 International Unit per square meter (IU·m2) of body surface, systemic route, and intratumoral infiltration of bleomycin at a dose of 0.25 IU per cubic centimeter (IU·cm3) of tumor surface. Considering the high selectivity of bleomycin for epithelial cells and the characteristics of tumor vascularization, electrical pulses were subsequently applied with an intensity of 1,000 volts per square centimeter (V·cm2), using different types of electrodes. Twenty eight days after the application of the therapy, the tumor masses were reduced by 50%, achieving an objective response to the applied treatment. edison.salazar.60@est.ucacue.edu.ec

Objective: To evaluate the feasibility of posterior maxillary teeth extraction buccal infiltration with or without the use of palatal injection. Material and Methods: A total of 70 patients underwent extraction of bilateral maxillary posterior teeth under 2% lignocaine hydrochloride with 1:2,00000 adrenaline infiltration in this single-centric split-mouth randomized trial. The test side was administered with a buccal infiltration of 2 mL of anesthetic alone. An extended waiting period of 10 minutes was given before the commencement of the procedure. A standard protocol was followed for the control side. A single operator performed all extractions. Results: A total of 140 posterior maxillary teeth were extracted. Patients marked pain perception on a visual analogue scale in three different instances. During the administration of injections for the test side, the pain score was less than that of the control side and was statistically significant. The overall pain during the extraction procedure was comparable and statistically insignificant. The overall success of the method was 90%. Conclusion: Extraction of posterior maxillary teeth was feasible with a single buccal infiltration without palatal injection in most cases using an extended waiting period. Dentists can attempt extraction without palatal injections with optimal success. However, the alternate technique could be used when there is a necessity for rescue palatal anesthesia.

Armero-Guayabal es un municipio agrícola y ganadero ubicado al norte del departamento del Tolima, este municipio alberga una población de 12,582 habitantes de estos el 80% viven de los productos agrícolas propios, y otros trabajando en estas áreas. La intención del proyecto Mercado Armero es establecer un punto de acopio venta de los productos autóctonos de los campesinos de la región, ya que la plaza actual no cuenta con buenas instalaciones y su emplazamiento se encuentra retirado de la zona de comercio del municipio. El mercado Armero tiene como meta no solo generar un espacio idóneo para el comercio de los campesino sino también convertirse en un punto de encuentro para los demás habitantes ya que se establece como un punto de partida para mejorar las relaciones interpersonales de los habitantes y consolidar así el comercio del municipio en el centro de este mismo. Palabras claves: Tolima, agrícolas, proyecto, mercado, autóctonos, Armero, campesinos, interpersonales. Armero-Guayabal is an agricultural and livestock municipality located in the north of the department of Tolima, this municipality has a population of 12,582 inhabitants of which 80% live from their own agricultural products, and others work in these areas. The intention of the Armero Market project is to establish a point of collection and sale of the local products of the farmers of the region, since the current market does not have good facilities and its location is far from the commercial area of the municipality. The goal of the Armero market is not only to generate an ideal space for the commerce of the farmers but also to become a meeting point for the other inhabitants since it is established as a starting point to improve the interpersonal relations of the inhabitants and thus consolidate the commerce of the municipality in the center of the municipality. Keywords: Tolima, agricultural, Market, Project, local, Amero, farmers, interpersonal. Arquitecto Pregrado

Purpose Breast cancer-specific survivorship care guidelines for the more than 3.8 million survivors in the U.S. are available, but implementation in clinical practice remains challenging. We examined current practice patterns and factors associated with guideline-concordant survivorship care among oncologists. Methods A national sample of medical oncologists, recruited using two databases, participated in a survey focused on practice patterns for breast cancer survivorship care. A “survivorship care composite score” was calculated for each respondent based on provision of services recommended in the survivorship guidelines. Descriptive statistics and multivariable linear regression analyses examined associations between physician and practice characteristics and composite scores. Results The survey was completed by 217 medical oncologists, with an overall response rate of 17.9% and eligibility rate of 56.9% for those who responded. Oncologists reported high engagement in evaluation of disease recurrence (78%). Performed less frequently were the provision of survivorship care plans (46%), assessment of psychosocial long-term and late effects (34%), and screening for subsequent cancers (34%). Lack of survivorship care training (p = 0.038) and not routinely informing patients about potential late effects (p = 0.003) were significantly associated with poorer survivorship care composite scores. Conclusions Despite the availability of disease-specific survivorship care guidelines, adherence to their recommendations in clinical practice is suboptimal. Survey results identified key gaps in survivorship care for breast cancer survivors, particularly related to subsequent primary cancers and psychosocial long-term and late effects. Implications for Cancer Survivors Improving the delivery of comprehensive survivorship care for the growing population of breast cancer survivors is a high priority. Disease-specific clinical guidelines for cancer survivorship provide valuable recommendations, but innovative strategies are needed to integrate them into the care of long-term breast cancer survivors.

BACKGROUND Microsatellite instability (MSI) is a hallmark of specific cancers and can be diagnosed using both tissue- and liquid-based approaches. When these tissue- and liquid-based approaches give differing results, they are known as discordant or being at variance. MSI-H tumors are well-researched candidates for treatment with programmed cell death protein 1 (PD-1) inhibitor-based immunotherapy, but the efficacy of immunotherapy in MSI-H discordant endometrial cancer, especially as first-line therapy, is not yet well documented in the literature. CASE REPORT A 67-year-old woman presented with a retroperitoneal mass positive for recurrent adenocarcinoma of endometrial origin. Her stage I endometrial adenocarcinoma 7 years ago demonstrated microsatellite stable (MSS) by immunohistochemical (IHC) stain and indeterminant due to insufficient tissue by Caris Next-Generation Sequencing (NGS). She then presented with a retroperitoneal mass that was MSI-H on IHC stain and Caris NGS, as well as MSI high on liquid biopsy @Guardant360 (@G360). The patient proceeded with pembrolizumab treatment 1 year ago and has sustained a complete clinical response at the time of writing. CONCLUSIONS Our case provides further evidence for the need to retest the microsatellite stability of metastatic sites, especially after a long disease-free survival. Here, we providing a literature review of case reports and a review of studies outlining discordance of testing modalities. Our case also highlights the importance of considering the use of immunotherapy as a first-line agent in patients who may have a poor ECOG performance status, as it can significantly improve their quality of life and reduce the number of adverse effects compared to chemotherapy.

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.

BackgroundResection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear.MethodsThe Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan-Meier analysis was performed for overall survival (OS) and recurrence-free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional-hazards regression was performed to identify risk factors associated with OS.ResultsA total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat-hepatectomy versus 38.3 months in the single-hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat-hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat-hepatectomy group, versus 9.8 months in the single-hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a “second breast cancer event”) using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm’s diagnostic accuracy against a manual patient record review (n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm’s performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures.

Purpose: Locoregional relapse in patients with head and neck squamous cell carcinoma (HNSCC) is common, approaching 50% for some subsites despite multimodality therapy. Salvage surgery is the standard of care, but able to achieve durable control in only a minority of patients. While adjuvant radiotherapy or chemo-radiotherapy is offered to select patients, this approach can be prohibitively toxic. Given the activity and tolerability of programmed death-1 inhibitors in metastatic HNSCC, we investigated the safety and efficacy of adjuvant nivolumab after salvage surgical resection. Patients and Methods: This was an open-label, multi-institutional phase II clinical trial (NCT03355560). Patients with recurrent, resectable HNSCC were enrolled within 6 weeks of salvage surgery. Six 28-day cycles of adjuvant nivolumab were planned. The primary endpoint was 2-year disease-free survival (DFS) more than 58%, based on an institutional historical control group of 71 patients with recurrent HNSCC who underwent salvage surgery. Results: Between February 2018 and February 2020, 39 patients were enrolled. At a median follow-up of 22.1 months, 2-year DFS was 71.4% [95% confidence interval (CI), 57.8–88.1] and the 2-year overall survival (OS) was 73% (95% CI, 58–91.8). Three of 39 (8%) patients experienced grade 3 treatment-related adverse events and 3 of 39 (8%) discontinued treatment due to side effects. Ten of 39 had locoregional recurrence, while 2 of 10 also had synchronous metastatic disease. There was no difference in DFS between PD ligand-1 (PD-L1)–positive and PD-L1–negative patients. There was a nonsignificant trend toward improved DFS in patients with high tumor mutational burden (P = 0.083). Conclusions: Adjuvant nivolumab after salvage surgery in locally recurrent HNSCC is well tolerated and showed improved DFS compared with historical controls.

Introduction Tumor Treating Fields (TTFields, 200 kHz) therapy is a noninvasive, locoregional cancer treatment approved for use in newly diagnosed glioblastoma (GBM), recurrent GBM, and malignant pleural mesothelioma. GBM patients with hydrocephalus may require implantation of a ventriculoperitoneal (VP) shunt, however, the current TTFields therapy label does not include the use of VP shunts in GBM patients due to insufficient safety data. This analysis evaluates the safety of TTFields therapy use in this population. Methods Unsolicited post-marketing global surveillance data from patients with GBM and a VP shunt (programmable/non-programmable) who received TTFields therapy between November 2012–April 2021 were retrospectively analyzed. Adverse events (AEs) were assessed using the Medical Dictionary for Regulatory Activities version 24.0. Results Overall, 156 patients with VP shunts were identified and included in this analysis. In total, 77% reported ≥ 1 AE; the most common TTFields therapy-related AEs were non-serious and localized, beneath-array skin AEs (43%). The incidence and categories of AEs were comparable between patients with or without VP shunts. Six patients with VP shunts experienced seven serious TTFields therapy-related AEs: skin erosion at the shunt site (n = 3); wound dehiscence at the shunt site (n = 2) and at the resection scar (n = 2). No shunt malfunctions were deemed related to TTFields therapy. Conclusions In the real-world setting, TTFields therapy in GBM patients with VP shunts demonstrated good tolerability and a favorable safety profile. There was no evidence that TTFields therapy disrupted VP shunt effectiveness. These results suggest TTFields therapy may be safely used in patients with VP shunts.

This study aimed to evaluate the performance of the 2017 8The cohort involved 300 patients affected by OTSCC treated with surgery. All cases were classified according to the 7According to the 7This study confirmed that the recent update of the 8th edition of the TNM (2020) improves stratification and identification of advanced tumours, reducing the number of T3 compared to the 2017 edition and increasing the number of patients with pT4. This improvement made by the updated edition may reduce the risk of skipping adjuvant therapy.Il carcinoma della lingua mobile: i cambiamenti della prognosi in base alla versione 2020 del sistema di classificazione AJCC/UICC TNM.Questo studio mira alla valutazione dell’efficacia predittiva dell’8ª edizione del TNM (2017) e dell’ultima versione aggiornata nel 2020 rispetto alla 7Il gruppo di studio consta di 300 pazienti affetti da carcinoma spinocellulare della lingua mobile trattati chirurgicamente. Tutti i casi sono stati classificati in base alla 7Secondo la 7Questo studio ha confermato che il recente aggiornamento dell’8

BackgroundPoly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.Primary ObjectiveTo determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.Study HypothesisOlaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.Trial DesignPhase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator’s choice.Major Eligibility CriteriaEligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.Primary EndpointThe dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.Sample SizeApproximately 200 patients will be enrolled in this study.Estimated Dates for Completing Accrual and Presenting ResultsEnrollment will be completed in 2024. Results will be presented in 2026.Trial RegistrationEudraCT 2021-000245-41NCT05255471

Background: Phyllodes tumors (PTs) of the breast are rare fibroepithelial tumors that are generally more prone to recurrence. Aims and objectives: This study aimed to assess the clinicopathological features, diagnostic modalities, and therapeutic interventions, along with their respective outcomes, to identify the factors associated with a recurrence of PTs of the breast. Methodology: A retrospective cohort and observational study was conducted, which entailed analyzing the clinicopathological data of patients who were previously diagnosed or presented with PTs of the breast between 1996 and 2021. Data included the total number of patients diagnosed with PTs of the breast and their ages, tumor grade on initial biopsy, tumor location (left or right breast), tumor size, therapeutic interventions carried out (including surgery—either mastectomy or lumpectomy—and adjuvant radiotherapy), final tumor grade, recurrence status, type of recurrence, and time to recurrence. Results: We analyzed data on a total of 87 patients who were pathologically proven to have PTs, and 46 patients (52.87%) were found to have recurrences. All patients were female, with a mean age at diagnosis of 39 years (range 15–70). Patients aged 40 years, with a rate of recurrence of 45.65% (n = 21/46). A total of 55.4% of patients presented with primary PTs and 44.6% had recurrent PTs at presentation. The average time to local recurrence (LR) from the completion of treatment was 13.8 months, whereas for systemic recurrence (SR), it was 15.29 months. Surgery (mastectomy/lumpectomy) was the major determinant for local recurrence (p < 0.05). Conclusion: Patients who received adjuvant radiotherapy (RT) had a minimal recurrence of PTs. Patients who were found to have a malignant biopsy on initial diagnosis (triple assessment) had a higher incidence of PTs and were more prone to SR than LR. Surgery was a determining factor in the increased rate of LR, with lumpectomy associated with a higher incidence of LR than mastectomy.

La nouvelle gouvernance locale exige la coalition de forces combinées des différents acteurs du local. De ce fait, l’implication des associations ; en tant que principale composante de l’économie sociale et solidaire ; au développement local, est considérée de nos jours un défi majeur pour l’état marocain.Indubitablement, au cours des dernières décennies, ces organisations de la société civile ont connu une croissance significative. Le renforcement de leurs capacités devient, dès lors, un enjeu de taille pour ces partenaires du développement. Cette problématique mène à s’interroger : quelles sont les capacités propres à ces associations, les capacités requises et que faut-il faire pour que celles-ci contribuent efficacement au développement du local ? Quels sont les efforts déployés dans ce sens au Maroc ? Dans ce travail notre contribution est de mener une réflexion générale et concrète pour comprendre le fonctionnement des associations marocaines, leurs capacités, les actions entreprises en vue de les renforcer et leurs retombées sur le local.

PURPOSE Both the performance characteristics of prostate-specific membrane antigen positron emission tomography and insurance approval improves with increasing prostate-specific antigen (PSA) level causing some physicians to delay post-radical prostatectomy salvage radiation therapy (sRT) after PSA failure. Yet, it is unknown for men with at most one high-risk factor (ie, pT3/4 or prostatectomy [p] Gleason score 8-10) whether a PSA level exists above which initiating sRT is associated with increased all-cause mortality (ACM)-risk and was investigated. METHODS Using a multinational database of 25,551 patients with pT2-4N0 or NXM0 prostate cancer, multivariable Cox regression analysis evaluated whether an association with a significant increase in ACM-risk existed when sRT was delivered above a prespecified PSA level beginning at 0.10 ng/mL and in 0.05 increments up to 0.50 ng/mL versus at or below that level. The model was adjusted for age at and year of radical prostatectomy, established prostate cancer prognostic factors, institution, and the time-dependent use of androgen deprivation therapy. RESULTS After a median follow-up of 6.00 years, patients who received sRT at a PSA level >0.25 ng/mL had a significantly higher ACM-risk (AHR, 1.49; 95% CI, 1.11 to 2.00; P = .008) compared with men who received sRT when the PSA was ≤0.25 mg/mL. This elevated ACM-risk remained significant for all PSA cutpoints up to 0.50 ng/mL but was not significant at PSA cutpoint values below 0.25 ng/mL. CONCLUSION Among patients with at most one high-risk factor, initiating sRT above a PSA level of 0.25 ng/mL was associated with increased ACM-risk.

L’attention portée au déploiement spatial des activités œuvrant à la transition écologique au sein des campagnes rurales et périurbaines a révélé leur important potentiel de mutation sociale et spatiale : le renouvellement des pratiques que la transition écologique induit réactive le local comme échelle pertinente pour construire des solutions concrètes ; il contribue en même temps à conforter des solidarités et des coopérations en réseaux déployés à d’autres échelles, régionale nationale et internationale ; cette transition ne se limite pas aux activités elles-mêmes, mais implique l’inscription spatiale de ces pratiques et ses relations dans des espaces à la fois plus resserrés et davantage déployés, des petits mondes interconnectés et elle ouvre de nouvelles perspectives de transformation de leurs espaces bâtis et ouverts. The focus on the spatial deployment of activities aimed at ecological transition in the rural and peri-urban countryside has revealed their significant potential for social and spatial change. The renewal of practices that the ecological transition revives the idea of the local as a relevant scale for building concrete solutions. It also contributes to strengthening solidarity and cooperation in networks operating at other scales, whether it be regional, national or international. This transition is not limited to the activities themselves, but implies the spatial inscription of these practices and relationships in spaces that are both compact and more widely dispersed—small interconnected worlds—opening up new perspectives for the transformation of their built and open spaces

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention.

Càncer de coll uterí; Platí; Topotecan Cáncer de cuello uterino; Platino; Topotecan Cervical cancer; Platinum; Topotecan Objective To determine whether a non‑platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma. Methods Gynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1–3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS. Results At the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91–1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82–1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86–1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86–1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75–1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones. Conclusions Topotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. This study was supported by the following National Cancer Institute and Genentech grants: NRG Oncology (1U10CA180822), NRG Operations (U10CA180868) and NCORP grant UG1CA189867.

PSICHE (NCT05022914) is a prospective trial to test a [68Ga]Ga- PSMA-11 PET/CT imaging tailored strategy. All evaluable patients had biochemical relapse after surgery and underwent centralized [68Ga]Ga-PSMA-11 PET/CT imaging. The treatment was performed according pre-defined criteria. Observation and re-staging at further PSA progression were proposed to patients with negative PSMA and previous postoperative RT. Prostate bed SRT was proposed to all patients with a negative staging or positive imaging within prostate bed. Stereotactic body radiotherapy (SBRT) to all sites of disease was used for all patients with pelvic nodal recurrence (nodal disease

Les secteurs manufacturiers de nombreux pays ont vu leurs parts dans les économies nationales décliner depuis plus de 20 ans, et le Québec n’en fait pas exception. Bouleversé par des ralentissements économiques et des signatures d’accords de libre-échange, ce secteur autrefois prédominant dans la province a vu son pourcentage de produit intérieur brut et sa proportion d’emploi continuellement diminué lors des dernières décennies. Plusieurs causes permettent d’expliquer ce déclin, telles que la libéralisation du commerce international, l’appréciation des devises et la délocalisation d’entreprises manufacturières. Cependant, les crises récentes, comme la pandémie de COVID-19 et les perturbations dans les chaînes d’approvisionnement internationales, ont démontré la pertinence d’avoir accès à des systèmes de productions locales afin de soutenir la résilience économique locale et une plus grande autonomie lors de ces crises. Dans ce contexte, ce mémoire cherche à explorer les leviers et les freins de la production locale de meubles et d’objets de maison au Québec, en s’attardant aux petites entreprises utilisant des échelles de production de moyenne série, une échelle particulièrement utilisée chez les PME, qui constitue la majorité des entreprises du secteur manufacturier québécois. Plus précisément, il pose la question suivante : quelles leçons tirer d’expériences d’entreprises œuvrant dans le secteur manufacturier de meubles produit localement au Québec à des échelles de production de moyenne série ? Afin de répondre à cette question, une recherche qualitative mettant de l’avant l’analyse documentaire et des entretiens semi-dirigés avec des personnes œuvrant dans des entreprises différentes possédant des expériences riches et pertinentes dans les mises en production de moyennes séries a permis de documenter ce secteur. Cette collecte de données a permis, dans un premier temps, de caractériser le domaine de production de meubles conçu et fabriqué localement, et, dans un second temps, d’identifier les grandes lignes de modèles de production viables dans une échelle de production de moyenne série. Les résultats de cette étude montrent que les d’entreprises intégrant l’ensemble des activités de fabrication à l’interne, et mettant de l’avant des types de productions variées (comme la fabrication à l’ordre combiné à la fabrication pour inventaire) sont en mesure d’être plus résilientes. De plus, celles qui entretiennent des partenariats avec des entreprises concurrentes seraient plus autonomes et entretiendraient des relations plus pérennes avec des fournisseurs locaux., The manufacturing sectors in many countries have seen their share of national economies decline over the past 20 years, and Quebec is no exception. Shaken by economic downturns and the signing of free trade agreements, this once-dominant sector in the province has seen its percentage of gross domestic product and its share of employment decline steadily over the past few decades. There are several reasons for this decline, such as the liberalization of international trade, currency appreciation and the relocation of manufacturing companies. However, recent crises, such as the COVID-19 pandemic and disruptions in international supply chains, have demonstrated the relevance of having access to local production systems to support local economic resilience and greater autonomy during these crises. In this context, this paper seeks to explore the levers and obstacles of local furniture and object production in Quebec, focusing on small firms using medium-scale production, a scale particularly used by SMEs, which constitute most firms in the Quebec manufacturing sector. More specifically, it asks the following question: what lessons can be learned from the experiences of firms operating in the manufacturing sector of locally produced furniture and objects in Quebec at medium production scales? To answer this question, a qualitative research based on documentary analysis and semi-directed interviews with people working in different companies with rich and relevant experiences in the production of medium-sized series allowed to document this sector. This data collection allowed, firstly, to characterize the field of production of locally designed and manufactured objects, and, secondly, to identify the main lines of viable production models in a scale of medium series production. The results of this study show that firms that integrate all manufacturing activities in-house and put forward various types of production (such as make-to-order combined with make-to-stock) are able to be more resilient. In addition, those that partner with competitive firms would be more self-sufficient and have more sustainable relationships with local suppliers.

International audience; Living with nuclear power means, for workers in the sector, enjoying comfortable living conditions in areas with low population density and, for those living near the sites, enjoying a certain urbanity in the countryside. But this requires having to deal with the uncertainties associated with this industry, namely its health and environmental risks: the effects forms of radioactivity that escape the senses have on humans, and the extension of the dangers of nuclear power from inside the installations outwards. These changes are accompanied by the building of specific categories of social classification at the local level. Indeed, the nuclear industry creates a labor force mixing natives and newcomers, while nuclear workers and other local residents have different understandings of nuclear risk. Such changes are the object of constant forms of renegotiation and become elements of insecure instability. The regulation of these dangers in our control society is itself the object of questioning about its effectiveness, its possible diversion for other purposes, in games internal to the sector or aimed above all at its external legitimacy, especially on an economic level. With the effect of making it difficult for families to project themselves on an intergenerational scale.; Vivre avec le nucléaire, c’est, pour les travailleurs du secteur et pour les riverains des sites, profiter de conditions de vie confortables dans des territoires à faible densité de population et d’une certaine urbanité à la campagne. Mais cela réclame de devoir composer avec les incertitudes lourdes associées à cette industrie à risques sanitaires et environnementaux : les effets sur l’homme d’une radioactivité qui échappe aux sens, et le prolongement des dangers du nucléaire de l’intérieur des installations vers l’extérieur. Il faut y ajouter le mouvement de construction de catégories de classement social à l’échelle locale à l’occasion de l’exploitation industrielle de l’atome avec une main-d’oeuvre mêlant autochtones et nouveaux venus, et les divergences d’appréciation des risques par les travailleurs du nucléaire et par les autres riverains. Ces mouvements connaissent des renégociations régulières qui sont facteurs d’instabilité insécurisante. Enfin, la régulation de ces dangers dans notre société du contrôle est elle-même objet d’interrogations sur son efficacité, sur son éventuel détournement à d’autres fins, dans des jeux internes au secteur ou visant par-dessus tout sa légitimité extérieure, notamment sur un plan économique. Avec pour effet de rendre difficile aux familles de se projeter à l’échelle intergénérationnelle dans ces territoires industriels.

BACKGROUND: Few studies (in other countries than the US) have reported on the efficacy and safety of dexmedetomidine for sedation of patients undergoing surgical or medical procedures under local anesthesia without intubation outside the intensive care unit. We performed a randomized, double-blind study in Japan. METHODS: Adult patients were randomly allocated to receive placebo, dexmedetomidine 0.5 μg/kg (DEX 0.5 group), or dexmedetomidine 1.0 μg/kg (DEX 1.0 group) over 10 min. Then, both dexmedetomidine groups received dexmedetomidine 0.2–0.7 μg/kg/h for maintaining an Observer’s Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients whose score exceeded this value. The primary endpoint was the percentage of patients who did not require rescue propofol to achieve and maintain an OAA/S score of ≤ 4. RESULTS: In total, 162 patients were included in the placebo (n = 53), DEX 0.5 (n = 53), and DEX 1.0 (n = 56) groups. Propofol was not required in significantly more patients in the dexmedetomidine 0.5 and 1.0 μg/kg groups (52.8% and 57.1%, respectively) compared with the placebo group (1.9%) (P < 0.001 for both). Common adverse events were protocol-defined hypotension, respiratory depression and bradycardia. The incidence of bradycardia was significantly higher in the DEX 0.5 (26.4%) and DEX 1.0 (30.4%) groups than in the placebo group (9.4%) (P = 0.041 and P = 0.008, respectively). CONCLUSION: We concluded that a loading dose of 0.5 or 1.0 μg/kg dexmedetomidine followed by infusion at a rate of 0.2–0.7 μg/kg/h provided effective and well-tolerated sedation in patients undergoing surgical or medical procedures under local anesthesia without intubation. Clinical trials.gov identifier: NCT01438931

Background Loco-regional treatments have improved the survival of patients with early hepatocellular carcinoma (HCC), but tumor relapse is a frequent event and survival rates remain low. Moreover, conflicting evidences address early HCC patients to surgery or radiofrequency ablation (RFA), with the clinical need to find predictive non-invasive biomarkers able to guide treatment choice and define patients survival. Methods Two independent case series of treatment-naive HCC patients treated with local RFA, and a cohort of 30 HCC patients treated with liver surgery were enrolled. On the basis of literature evidence, we customized a panel of 21 miRNAs correlated with relapse and prognosis after local curative treatment of HCC. Results Expression levels of let-7c predict tumor relapse after RFA; we also investigated the same panel in a small cohort of HCC patients undergoing surgery, finding no statistically significance in predicting tumor relapse or survival. Moreover, interaction test indicated that let-7c expression levels are predictive for identifying a subset of patients that should be addressed to surgery. Conclusion Results from this study could predict prognosis of early HCC patients, helping to address early HCC patients to surgery or RFA treatment.

Localisation, as it aims to shift power in the humanitarian system, will involve the increased inclusion of local faith actors, those national and local faith-affiliated groups and organisations that are often first, and last, responders in crises and have been responding in humanitarian contexts for many years, but often in parallel to humanitarian coordination mechanisms. In primary research in South Sudan with local faith actors and international humanitarian actors, this article aims to examine the inroads and barriers to local faith actor involvement in the humanitarian system and the realisation of localisation with local actors such as these. The research is based on an ethnographic study in which researchers were imbedded in a humanitarian project that aimed to help bridge divides between local faith actors and the international humanitarian system. The findings are based on one-on-one and group interviews with 89 participants from a range of international and local, and faith and secular, organisations. Findings indicate that local faith actors are active in responding to crises and want to be linked to the humanitarian system, but they feel distanced from it and pigeonholed as local faith actors. Formalisation through the appropriate registration systems and then training and networking with the humanitarian system helped them build legitimacy and feel confident to participate in humanitarian coordination. International humanitarian actors can help bridge barriers by understanding and connecting with the local faith actors and challenging their own assumptions about who local faith actors are.

This prospective clinical trial evaluated the effects of epidural anesthesia (EA) placed at the lumbosacral compared to the L5-L6 junction in dogs undergoing hindlimb orthopedic surgery. In all, 98 dogs were randomly assigned to receive injection at either L7-S1 (LS group) or L5-L6 (LL group) at the same local anesthetic regimen (1 mg/kg bupivacaine 0.5% and 0.1 mg/kg morphine 1%). Fentanyl (1 µg/kg) was the intraoperative rescue analgesia (iRA) administered if mean arterial pressure increased by 30% above pre-stimulation value. Procedural failure, iRA, hypotension, motor block resolution, and postoperative side effects were recorded. There were 7/47 (15%) epidural procedural failures in the LS group and 8/51 (16%) (P=1.00) in the LL group; iRA was administered in 21/40 (52%) LS group dogs and in 13/43 (30%) LL group dogs, respectively (P=0.047). The incidence of hypotension was 10/40 (25%) and 16/43 (37%) in the LS group and the LL group, respectively (P=0.25). Proprioceptive residual deficit at 8 hr after EA was recorded in 3/26 (12%) in group LS dogs and in 13/26 (50%) group LL dogs, respectively (P=0.01). The proprioceptive residual deficit at 24 hr in one dog (LL group) resolved within 36 hr. No episodes of postoperative urinary retention, pruritus or neurological damage were recorded. The L5-L6 EA decreased significantly iRA but delays the proprioceptive recovery time. Further studies are needed to determine whether a lower bupivacaine dose reduces the duration of the residual block retaining the same incidence of iRA.

Background/Aim: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. Patients and Methods: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). Results: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p

Contains fulltext : 249569.pdf (Publisher’s version ) (Open Access) AIM: Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC. PATIENTS AND METHODS: A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs. No prior systemic treatments were required. Patients started cabozantinib 60 mg once daily. The primary outcome was the objective response rate (ORR). Secondary outcomes included survival, safety and quality of life. Per Simon-two-stage design, depending on efficacy, a maximum of 43 patients would be included. RESULTS: In total, 25 patients were included until premature closure owing to severe toxicity. Six patients (24%) had grade 3-5 wound complications, occurring at a median of 7.1 months on cabozantinib treatment (range 2.1-12.6). Remarkably, four of these six patients developed this complication in the area prior exposed to high-dose radiotherapy. Other grade ≥3 adverse events in >1 patient were hypertension (20%), diarrhoea (8%) and dehydration (8%). Twenty-one patients were evaluable for response; 1/15 ACC (ORR: 7%); 1/4 SDC and 0/2 patients with other miscellaneous SGC responded. Median progression-free survival was 9.4 months (95% confidence interval [CI] 7.4-11.4 months), 7.2 months (95%CI 0.0-15.1) and 6.9 months (95%CI 0.0-15.1), respectively. CONCLUSION: This study showed too many severe cabozantinib-associated wound complications in patients with SGC, especially in prior irradiated areas. Therefore, the study closed prematurely. The efficacy in the limited number of evaluable patients was low to moderate. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov: NCT03729297.

Es común afirmar que la local representa la dimensión política más cercana a la ciudadanía y la más idónea para determinar, en lo cotidiano y en lo colectivo, su bienestar. Esta premisa, sin embargo, puede darse solo si se entienden satisfechos algunos prerrequisitos básicos que atañen tanto a cada ciudadano/a, como a los poderes públicos llamados a administrar la política local, es decir: que exista una voluntad de participar crítica y activamente y que existan las condiciones idóneas, efectivas y reales para lograr esa participación. Este estudio analiza la participación política local en Italia, desde los años ‘70 en adelante, y busca dar respuestas a un fenómeno preocupante y extremadamente actual: el abstencionismo. Recibido: 10.11.2021Aceptado: 13.12.2021

Using examples from Anglican missions in the Great Lakes region of Africa this article explores the roles of African Protestant missionaries in the modern era. It argues that many committed African Christians understood themselves to be missionaries and examines the nature of their missionary activity. Those who called themselves missionaries evangelised outside their own ethnic group. They were engaged in regional and transnational developments. The article attends to local and regional historical processes to show how African missionary activities were infused with transnational notions of belonging to a world religion.

There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time of surgery remain high even after complete resection of tumors currently categorized as 'early stage.' A 14-gene quantitative PCR-based expression profile has been extensively validated to better identify patients at high-risk of 5-year mortality after surgical resection than conventional staging - mortality that almost always results from previously undetectable metastases. Furthermore, prospective studies now suggest a predictive benefit in disease-free survival when the assay is used to guide adjuvant chemotherapy decisions in early-stage non-small-cell lung cancer patients.Lay abstract There is a need for improvement in the way early-stage non-small-cell lung cancers are staged and treated because many patients with ‘early-stage’ disease suffer high rates of cancer recurrence after surgery. In recent years, a specialized test has been developed to allow better characterization of a tumor's risk of recurrence based on the genes being expressed by tumor cells. Use of this test, in conjunction with standard staging methods, is better able to identify patients at high risk of cancer recurrence after surgery. Evidence suggests that giving chemotherapy to patients at high risk of recurrence after surgery reduces recurrence rates and improves long-term patient survival.

Private international law plays an important role in defining applicable law and regulating private international law relations. Foreign law is significantly different from local law. Judges do not have the right to change the content of foreign law, they simply have the opportunity to reject or apply foreign law. When a judge is obliged to make a decision based on the rules of national law in the process of legal proceedings, it is clear that the law of a foreign country can- not enjoy the same status. The issue of determining the content of foreign law and its application remains one of the most problematic issues in the private international law of countries around the world. French case law has gone through a difficult and controversial path to formulate a decisive position on the application of foreign law. Resolving this problem was especially important for France, as the courts of this country have to deal with a large number of international litigation cases. The basis for the application of foreign law is the choice of French private international law rules, as a particular legal relationship is subject to regulation by a foreign legal system. Thus, French courts apply foreign law to administer high-quality justice, as finding the right solution lies in applying foreign law.

Lebanon is one of the Mediterranean countries that are devastated by economic crisis. Knowing that generic medications are less costly when compared to brands, it is crucial to assess patients’ understanding and views regarding these medications. A 25-item self-administered anonymous questionnaire was distributed to a total of 421 participants. The questionnaire appraised participants’ knowledge and perceptions about generics versus brand medications, in addition to their perceptions and attitudes towards generic substitution. Most respondents agreed that generics are not inferior to their brand equivalents in terms of quality, efficacy and safety (66%, 68.9%, and 66.7%, respectively). On the other hand, 79.4% (n=334) accepted generic substitution for minor ailment medications, whereas, only 56.1% (n=236) accepted this substitution for their chronic medications. As a conclusion, the uncertainty about the use of generic medications, particularly those treating chronic illness is still an obstacle to overcome.

Les valeurs, les représentations et les symboles alimentaires circulent entre les villes et les campagnes sénégalaises depuis la colonisation. La présence d’un plat partagé par la majorité des Sénégalais et consommé presque quotidiennement par une large frange de cette population constitue une occasion de comprendre les tensions engendrées par la consommation de ce plat. L’accès à l’information sanitaire à travers les médias et les structures sanitaires font du ceebu jën un « plat à controverses ». Socialement, il est le plat servi lorsque l’on reçoit des invités, le plat autour duquel se crée et s’entretient le lien social. Nutritionnellement, la grande quantité d’huile et de bouillons en cube en font un responsable désigné de l’augmentation de la prévalence des maladies cardiovasculaires, de l’obésité, etc. Les résultats de cette étude s’appuient à la fois sur une enquête qualitative (entretiens approfondis et répétés, complétés par des observations dans le Ferlo et à Dakar) et sur une enquête quantitative (questionnaire à Dakar), toutes deux concernant l’alimentation domestique. Food values, representations, and symbols have been circulating between Senegalese cities and countryside since colonization. The presence of a dish shared by the majority of Senegalese and consumed almost daily by a significant section of this population provides an opportunity to understand the tensions generated by the consumption of this dish. Access to health information through the media and public health facilities make the ceebu jën a “controversial dish.” Socially, it is the dish served when one receives guests, the dish around which social bonds are created and maintained. Nutritionally, the large quantity of oil and bouillon cubes have caused the dish to be associated with the increase in the prevalence of cardiovascular diseases, obesity, etc. The results of this study are based on both a qualitative survey (in-depth and repeated interviews supplemented by observations in Ferlo and Dakar) and on a quantitative survey (questionnaire in Dakar), both concerning domestic food.

La question posée porte sur la capacité d’adaptation des halles à marée face aux fluctuations de l’offre et des cours du poisson dans le contexte des confinements en 2020. Le chiffre d’affaires national des premiers marchés a décliné de 18 % par rapport à la moyenne des trois années précédentes. La méthode de décomposition du chiffre d’affaires démontre que la valeur des productions traduit une stratégie de quantité et plus rarement une action sur les prix. Des enquêtes auprès des responsables de halles à marée apportent une lecture complémentaire, voire différente de celle des statistiques de vente. La discussion des résultats soulève d’une part le risque de biais informationnel pour une analyse limitée à une approche quantitative, d’autre part la menace potentielle des ventes directes sur les halles à marée. The question raised concerns the capacity of the fish markets to adapt to the fluctuations in supply and fish prices caused by the first confinement and amplified by the second in 2020. The national turnover of the first markets declined by 18 % compared to the average of the previous three years. The method of breaking down turnover shows that the value of production reflects a strategy on quantity and more rarely a price policy. Surveys of fish market managers provide a complementary even different understanding to that of the sales statistics. The discussion of the results raises two major questions. The first deals with the informational bias when the analysis is limited to a quantitative approach to production statistics. The second is the question of the potential threat of direct sales to fish markets.

La història local o comarcal es pot abordar des de diferents perspectives si volem conèixer tot un ventall d'assumptes que ens són necessaris per a vincular el passat amb el present, e inclús amb el futur. Analitzar el patrimoni cultural, la societat, les conjuntures econòmiques, la política, el govern, els sistemes productius, l'art, la geografia, etc., és un reconeixement i enfortiment de les nostres identitats locals que ens permetrà adaptar-nos a una societat cada vegada més global i mudant. L'Assemblea d'Història de la Ribera celebrada a Alberic ens ha permet endinsar-nos en el coneixement de la geologia, del patrimoni arqueològic i arquitectònic, de les oligarquies socials, de la conflictivitat social, de la dona i d'alguns temes culturals que evidencien el potencial de la història comarcal en l'avanç de la cognició dels nostres arrels. Els capítols d'aquest llibre cerquen la història local des de diferents punts de vista, i estudien l'escenari de la comarca de la Ribera del Xúquer en el context de la història valenciana.Desitgem que el lector trobe aportacions en les que puga gaudir i incorporar al seu coneixement, i si és historiador poder ampliar el context de les seues investigacions, ja que des de la individualitat assumim i construïm la nostra identitat.

We analyze the dynamics of a light scalar field responsible for the μ term of the Higgs potential and coupled to matter via the Higgs-portal mechanism. We find that this dilaton model is stable under radiative corrections induced by the standard model particle masses. When the background value of the scalar field is stabilized at the minimum of the scalar potential, the scalar field fluctuations only couple quadratically to the massive fields of the standard model preventing the scalar direct decay into standard model particles. Cosmologically and prior to the electroweak symmetry breaking, the scalar field rolls down along its effective potential before eventually oscillating and settling down at the electroweak minimum. These oscillations can be at the origin of dark matter due to the initial misalignment of the scalar field compared to the electroweak minimum, and we find that, when the mass of the scalar field is less than the electron volt scale and acts as a condensate behaving like dark matter on large scales, the scalar particles cannot thermalize with the standard model thermal bath. As matter couples in a composition-dependent manner to the oscillating scalar, this could lead to a violation of the equivalence principle aboard satellites such as the MICROSCOPE experiment and the next generation of tests of the equivalence principle. Local gravitational tests are evaded thanks to the weakness of the quadratic coupling in the dark matter halo, and we find that, around other sources, these dilaton models could be subject to a screening akin to the symmetron mechanism. We analyse the dynamics of a light scalar field responsible for the $\mu$ term of the Higgs potential and coupled to matter via the Higgs-portal mechanism. We find that this dilaton model is stable under radiative corrections induced by the standard model particle masses. When the background value of the scalar field is stabilised at the minimum of the scalar potential, the scalar field fluctuations only couple quadratically to the massive fields of the standard model preventing the scalar direct decay into standard model particles. Cosmologically and prior to the electroweak symmetry breaking, the scalar field rolls down along its effective potential before eventually oscillating and settling down at the electroweak minimum. These oscillations can be at the origin of dark matter due to the initial misalignment of the scalar field compared to the electroweak minimum, and we find that, when the mass of the scalar field is less than the eV scale and acts as a condensate behaving like dark matter on large scales, the scalar particles cannot thermalise with the standard model thermal bath. As matter couples in a composition-dependent manner to the oscillating scalar, this could lead to a violation of the equivalence principle aboard satellites such as the MICROSCOPE experiment and the next generation of tests of the equivalence principle. Local gravitational tests are evaded thanks to the weakness of the quadratic coupling in the dark matter halo, and we find that, around other sources, these dilaton models could be subject to a screening akin to the symmetron mechanism.

Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment. Although molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq, as well as gene expression and DNA methylation analysis in primary and relapsed ependymoma tumors, to identify chromosomal conformations and regulatory mechanisms associated with aberrant gene expression. In particular, we observe the formation of new topologically associating domains (‘neo-TADs’) caused by structural variants, group-specific 3D chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Through inhibition experiments, we validate that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models in a group-specific manner. Thus, this study extends our ability to reveal tumor-dependency genes by 3D genome conformations even in tumors that lack targetable genetic alterations.

PRIF Report, 2023/03, How do African citizens experience and evaluate African regional inter­ventions? This re­search report exa­mines the case of The Gam­bia to assess local percep­tions of the African Union and ECOWAS, particu­larly of their inter­ventions in that country since 2016. It is the result of colla­bora­tive and empiri­cally comprehen­sive research carried out across the country in 2021/2022. We demon­strate that percep­tions of the interven­tions in The Gambia are complex and diverge starkly, at times even contra­dicting each other. We explain this com­plexity as resul­ting from spatial, tempo­ral, and sociopo­litical factors that affect how these Afri­can regio­nal inter­ventions are (diffe­rently) perceived.

In this research note, we present results from a review of research on local resilience in relation to radicalization in public health, social work, crisis management, and community policing using terrorism studies as a point of departure. In order to identify agreements between literatures, we focus on how local resilience is understood, how it is said to be promoted, and how this knowledge could be synthesized. We show that resilience by and large is understood as both a process and a capacity underpinned by cooperation, social networks, and community resources and that an initial mapping of existing strengths and resources is pivotal for local resilience-building.