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E-Kelurahan is a web-based application used for document publishing at Kelurahan. This study stems from the many problems of the implementation of e-Kelurahan in Padang City including low user access, problem access, and e-Kelurahan limitations in online service delivery. The study aims to analyze the implementation of the e-kelurahan program in Padang City with more complex components. The analysis is carried out on technical site development, internal government, and client perspectives. The research method used descriptive qualitative. The theory is the Six Dimensional Assessment Tool (6DAT) for analyzing the Effectiveness of e-Government. These six dimensions are used as variable Security systems, Integrated Database Development, Intra-Agency Hierarchical Integration, Inter-Agency Lateral Coordination, Interactive Public Access, and Transparency of Government Structure and Process. According to the findings of this study, the implementation of the e-Kelurahan in Padang City is still ineffective. Even though the e-Kelurahan application is being improved to be more secure, it has an integrated database that is credible and up to date, and lateral relationships through joint partnerships are running smoothly, on the other hand, user experience is less concerned. however communication facilities to internal parties that are not provided to the public, in the lack of transparency of processes and structures, in the lack of interactivity of e-Kelurahan, and most importantly, in the lack of efficient access. It can be concluded, both in terms of applications, the organizers and the public are still in the transition stage to transform to digital.

Malnutrition is a prevalent problem in patients with cancer and is associated with poor prognosis. The European Society for Clinical Nutrition and Metabolism (ESPEN) recommends the provision of nutritional support and evaluation. This study aims to describe the nutritional management of patients with cancer, including assessment of adherence, from the perspective of both patients and healthcare professionals (HCPs).A cross-sectional descriptive observational study was carried out through two surveys addressed to patients and HCPs.A total of 230 cancer patients and 461 HCPs completed the questionnaire. The survey found 55.0% of patients experienced eating problems during treatment and 64.0% reported sequelae affecting nourishment. However, 60.1% of patients and 42.6% of HCPs indicated that nutritional status is not generally assessed. While 86.6% of HCPs stated that nutritional information is provided to patients, only 33.5% of patients reported having received it. Regarding nutritional adherence, 87.4% of HCPs stated that it is assessed whereas only 49.2% of patients receiving nutritional supplements confirmed this. General discomfort or gastrointestinal problems were the main issues hampering correct adherence perceived by both patients (41.8%) and HCPs (95.4%).Our study demonstrate that different perceptions exist between patients and HCPs about nutritional management in cancer and suggests that in Spain nutritional approach is suboptimal in terms of screening/assessment of malnutrition, nutritional information provided to the patient, nutritional intervention and assessment of adherence to nutritional support. Therefore, measure should be taken to foster the adoption of ESPEN recommendations in clinical practice and to promote nutritional education of HCPs.

Background: Studies on the value of a staging laparoscopy in detecting metastases in gastric cancer patients show great variation. This study investigates the avoidable surgery rate in patients with and without a staging laparoscopy scheduled for surgery with curative intent. Methods: This population-based cohort study included all patients with an intentional resection for a potentially curable gastric adenocarcinoma, between 2011 and 2016, registered in the Dutch Upper GI Cancer audit. Patients with and without a staging laparoscopy were compared. The primary outcome was the avoidable surgery rate (detection of metastases and/or locoregional non-resectable tumor during intentional gastrectomy). Secondary outcomes were the negative predictive value, postoperative morbidity and pathology parameters. Results: 2849 patients who underwent an intentional gastrectomy were included. 414 of 2849 (14.5%) patients underwent a staging laparoscopy before initiation of treatment. The avoidable surgery rate was 16.2% in the staging laparoscopy group, compared to 8.5% in the non-staging group (P < 0.001), resulting in a negative predictive value of 83.8%. The avoidable surgery rate remained significantly different after correction for possible confounders. The main reason for not executing the gastrectomy was the presence of distant metastasis in both groups. cT and cN stage were significantly higher in patients who underwent a staging laparoscopy. Conclusions: The staging laparoscopy group had a higher cTN and pTN stage, implicating selection of patients with more advanced disease for a staging laparoscopy. Despite the staging laparoscopy, a higher rate of avoidable surgery was found, suggesting a low sensitivity for detecting metastases or locoregional non-resectability in this patient group.

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions. The unusual circumstances of the pandemic meant studies such as RECOVERY were opened almost immediately and recruited record numbers of participants. However, trial teams were required to make concessions and adaptations to these studies to ensure recruitment was rapid and broad. As these are relevant to cancer trials that enrol patients with similar risk factors, we have added three new recommendations to our original ten: employing pragmatism such as using focused information sheets and collection of only the most relevant data; minimising negative environmental impacts with paperless systems; and using direct-to-patient communication methods to improve uptake. These recommendations can be applied to all oncology CID trials to improve their inclusivity, uptake and efficiency. Above all, the success of CID studies during the COVID-19 pandemic underscores their efficacy as tools for rapid treatment evaluation.

Understanding predictors of parents' willingness to vaccinate their children appears fundamental to promote vaccine acceptability, especially in a pandemic scenario. The present study aimed to investigate the role of conspiracy beliefs and absolutist thinking in parental attitude toward COVID-19 vaccine, and the predictive role of parents' individual differences on decisions against children's vaccination. An online survey was administered to 415 parents of children aged 5-11, at the very beginning of the vaccination targeting this population in Italy. Results showed that absolutism predicted the tendency to believe in conspiracies, associated with a negative attitude toward the COVID-19 vaccine administration to children. Moreover, mothers were less willing to vaccinate children and parents of children aged 5-7 were more hesitant, or even against vaccination, than parents of older children. Finally, the worry about consequences of COVID-19 infection on children's health facilitated vaccine adherence. These findings contribute to deepening mechanisms regarding the vaccine acceptability.

Contains fulltext : 291249.pdf (Publisher’s version ) (Open Access) Pluripotency describes the ability of stem cells to differentiate into derivatives of the three germ layers. In reporting new human pluripotent stem cell lines, their clonal derivatives or the safety of differentiated derivatives for transplantation, assessment of pluripotency is essential. Historically, the ability to form teratomas in vivo containing different somatic cell types following injection into immunodeficient mice has been regarded as functional evidence of pluripotency. In addition, the teratomas formed can be analyzed for the presence of malignant cells. However, use of this assay has been subject to scrutiny for ethical reasons on animal use and due to the lack of standardization in how it is used, therefore questioning its accuracy. In vitro alternatives for assessing pluripotency have been developed such as ScoreCard and PluriTest. However, it is unknown whether this has resulted in reduced use of the teratoma assay. Here, we systematically reviewed how the teratoma assay was reported in publications between 1998 (when the first human embryonic stem cell line was described) and 2021. Our analysis of >400 publications showed that in contrast to expectations, reporting of the teratoma assay has not improved: methods are not yet standardized, and malignancy was examined in only a relatively small percentage of assays. In addition, its use has not decreased since the implementation of the ARRIVE guidelines on reduction of animal use (2010) or the introduction of ScoreCard (2015) and PluriTest (2011). The teratoma assay is still the preferred method to assess the presence of undifferentiated cells in a differentiated cell product for transplantation since the in vitro assays alone are not generally accepted by the regulatory authorities for safety assessment. This highlights the remaining need for an in vitro assay to test malignancy of stem cells.

BackgroundCurrently, follow-up protocols are applied equally to men on active surveillance (AS) for prostate cancer (PCa) regardless of findings at their initial follow-up biopsy. To determine whether less intensive follow-up is suitable following negative biopsy findings, we assessed the risk of converting to active treatment, any subsequent upgrading, volume progression (>33% positive cores), and serious upgrading (grade group >2) for negative compared with positive findings on initial follow-up biopsy.Methods13,161 men from 24 centres participating in the Global Action Plan Active Surveillance Prostate Cancer [GAP3] consortium database, with baseline grade group ≤2, PSA ≤ 20 ng/mL, cT-stage 1-2, diagnosed after 1995, and ≥1 follow-up biopsy, were included in this study. Risk of converting to treatment was assessed using multivariable mixed-effects survival regression. Odds of volume progression, any upgrading and serious upgrading were assessed using mix-effects binary logistic regression for men with ≥2 surveillance biopsies.Results27% of the cohort (n = 3590) had no evidence of PCa at their initial biopsy. Over 50% of subsequent biopsies in this group were also negative. A negative initial biopsy was associated with lower risk of conversion (adjusted hazard ratio: 0.45; 95% confidence interval [CI]: 0.42-0.49), subsequent upgrading (adjusted odds ratio [OR]: 0.52; 95%CI: 0.45-0.62) and serious upgrading (OR: 0.74; 95%CI: 0.59-92). Radiological progression was not assessed due to limited imaging data.ConclusionDespite heterogeneity in follow-up schedules, findings from this global study indicated reduced risk of converting to treatment, volume progression, any upgrading and serious upgrading among men whose initial biopsy findings were negative compared with positive. Given the low risk of progression and high likelihood of further negative biopsy findings, consideration should be given to decreasing follow-up intensity for this group to reduce unnecessary invasive biopsies.

BackgroundClinical data collection related to prostate cancer (PCa) care is often unstructured or heterogeneous among providers, resulting in a high risk for ambiguity in its meaning when sharing or analyzing data. Ontologies, which are shareable formal (i.e., computable) representations of knowledge, can address these challenges by enabling machine-readable semantic interoperability. The purpose of this study was to identify PCa-specific key data elements (KDEs) for standardization in clinic and research.MethodsA modified Delphi method using iterative online surveys was performed to report a consensus agreement on KDEs by a multidisciplinary panel of 39 PCa specialists. Data elements were divided into three themes in PCa and included (1) treatment-related toxicities (TRT), (2) patient-reported outcome measures (PROM), and (3) disease control metrics (DCM).ResultsThe panel reached consensus on a thirty-item, two-tiered list of KDEs focusing mainly on urinary and rectal symptoms. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was considered most robust for PROM multi-domain monitoring, and granular KDEs were defined for DCM.ConclusionsThis expert consensus on PCa-specific KDEs has served as a foundation for a professional society-endorsed, publicly available operational ontology developed by the American Association of Physicists in Medicine (AAPM) Big Data Sub Committee (BDSC).

Persimpangan adalah bagian terpenting dari jalan perkotaan, karena sebagian besar dari efisiensi, keamanan, kecepatan, dan tingkat pelayanan jalan bergantung dari perencanaan persimpangannya. Dengan demikian diperlukan adanya manjemen lalu lintas yang terarah untuk mengatur kelancaran arus lalu lintas. Gambaran diatas merupakan salah satu permasalahan yang terjadi pada beberapa simpang empat tak bersinyal Jalan Cempaka. Pada Jalan utama Cempaka ini banyak terdapat pertokoan, perdagangan, pendidikan, tempat ibadah dan rumah masyarakat sekitar yang bisa menyebabkan arus lalu lintas yang cukup sibuk dan terjadi tundaan juga antrian dibeberapa persimpangan. Tujuan dari penelitian ini adalah menganalisis kinerja simpang tak bersinyal dan memberikan alternatif pemecahan masalah dengan acuan Pedoman Kapasitas Jalan Indonesia (PKJI) 2014. Prosedur penelitian yang digunakan dalam penelitian ini adalah survei lapangan secara langsung untuk mendapatkan data primer dan data sekunder. Berdasarkan hasil dari analisis simpang yaitu lokasi 1 nilai tundaan simpang sebesar 10,222 detik/skr atau pada tingkat pelayanan B dan Nilai peluang antrian sebesar 8% - 19,494% dengan derajat kejenuhan Dj = 0,413 (Dj ≤ 0,85), lokasi 2 nilai tundaan simpang sebesar 13,262 detik/skr atau pada tingkat pelayanan C dan Nilai peluang antrian sebesar 23% - 46% dengan derajat kejenuhan Dj = 0,761 (Dj ≤ 0,85). Arus belok kanan ≥200 kend/jam dengan kondisi tersebut alternatif yang dilakukan yaitu dengan memasang APILL, lokasi 3 nilai tundaan simpang sebesar 8,596 detik/skr atau pada tingkat pelayanan C dan Nilai peluang antrian sebesar 7% - 19% dengan derajat kejenuhan Dj = 0,404 (Dj≤ 0,85), lokasi 4 nilai tundaan simpang sebesar 11,088 detik/skr atau pada tingkat pelayanan C dan Nilai peluang antrian sebesar 12% - 27% dengan derajat kejenuhan Dj = 0,533 (Dj ≤ 0,85). Intersections are the most important part of urban roads, because most of the efficiency, safety, speed, and service level of roads depend on the intersection planning. Thus, it is necessary to have a directed traffic management to regulate the smooth flow of traffic. The picture above is one of the problems that occur at several unsignalized intersections on Jalan Cempaka. On the main street of Cempaka, there are many shops, trades, education, places of worship and houses of the surrounding community which can cause quite busy traffic flow and delays and queues at several intersections. The purpose of this study is to analyze the performance of unsignalized intersections and provide alternative solutions to problems with reference to the 2014 Indonesian Road Capacity Guidelines (PKJI). The research procedure used in this study was a direct field survey to obtain primary and secondary data. Based on the results of the intersection analysis, namely location 1, the intersection delay value is 10.222 seconds/cur or at service level B and the queue opportunity value is 8% - 19.494% with the degree of saturation Dj = 0.413 (Dj ≤ 0.85), location 2 the value of the intersection delay of 13,262 seconds/skr or at service level C and the queue probability value is 23% - 46% with the degree of saturation Dj = 0.761 (Dj ≤ 0.85). Right turn flow 200 vehicles/hour with these conditions the alternative is to install APILL, location 3 intersection delay value is 8.596 seconds/skr or at service level C and queue probability value is 7% - 19% with saturation degree Dj = 0.404 (Dj≤ 0.85), location 4, the intersection delay value is 11.088 seconds/skr or at service level C and the queue probability value is 12% - 27% with the degree of saturation Dj = 0.533 (Dj ≤ 0.85).

International audience; Introduction - Patients treated for malignancy are considered at risk of severe COVID-19. This exceptional pandemic has affected countries on every level, particularly health systems which are experiencing saturation. Like many countries, France is currently greatly exposed, and a complete reorganization of hospitals is ongoing. We propose here adaptations of diagnostic procedures, therapies and care strategies for patients treated for digestive cancer during the COVID-19 epidemic. Methods - French societies of gastroenterology and gastrointestinal (GI) oncology carried out this study to answer two main questions that have arisen (i) how can we limit high-risk situations for GI-cancer patients and (ii) how can we limit contact between patients and care centers to decrease patients' risk of contamination while continuing to treat their cancer. All recommendations are graded as experts' agreement according to the level of evidence found in the literature until March 2020. Results - A proposal to adapt treatment strategies was made for the main GI oncology situations. Considering the level of evidence and the heterogeneous progression of the COVID-19 epidemic, all proposals need to be considered by a multidisciplinary team and implemented with patient consent. Conclusion - COVID-19 epidemic may significantly affect patients treated for digestive malignancies. Healthcare teams need to consider adapting treatment sequences when feasible and according to the epidemic situation.

Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (, SCOPUS: ar.j, info:eu-repo/semantics/published

Peer reviewed: True, Funder: Committee of Preventive Healthcare of Companion Animals, Histiocytic sarcoma (HS) is an aggressive malignant tumor of histiocytes, which can affect almost any organ in the body and is characterized by a broad array of tumor locations and clinical presentations. So far, no complete overview exists of the array of clinical aspects of HS in specific dog breeds in large groups. Therefore, we investigated the clinical characteristics of HS in a population of Bernese Mountain Dogs (BMD; n = 365) and Flat-Coated Retrievers (FCR; n = 289), which are two of the most affected dog breeds. Cases were selected from databases from different pathology services, and clinical information was retrospectively collected for each case. Localized HS was reported significantly more frequently in the FCR (60.6%) than in the BMD (39.2%), and disseminated HS was recorded significantly more frequently in the BMD (60.8%) than in the FCR (39.4%). Lameness was seen more often in FCR than in BMD, and the vast majority (78.1%) of LHS leading to lameness was located in the front legs in the FCR, while in the BMD, there was a more even distribution. BMD had significantly more often leukocytosis and thrombocytopenia, even corrected for the type of HS, than FCR. No significant difference in the frequency of anemia was recorded between BMD and FCR. In those dogs in which blood examination was performed, hypercalcemia was diagnosed in 15 BMD, while none of the FCR had hypercalcemia. The new information provided in this study can aid the diagnostic process and allow for prompt treatment recommendations.

Background Up to 80% of cases of prostate cancer present with multifocal independent tumour lesions leading to the concept of a field effect present in the normal prostate predisposing to cancer development. In the present study we applied Whole Genome DNA Sequencing (WGS) to a group of morphologically normal tissue (n = 51), including benign prostatic hyperplasia (BPH) and non-BPH samples, from men with and men without prostate cancer. We assess whether the observed genetic changes in morphologically normal tissue are linked to the development of cancer in the prostate. Results Single nucleotide variants (P = 7.0 × 10–03, Wilcoxon rank sum test) and small insertions and deletions (indels, P = 8.7 × 10–06) were significantly higher in morphologically normal samples, including BPH, from men with prostate cancer compared to those without. The presence of subclonal expansions under selective pressure, supported by a high level of mutations, were significantly associated with samples from men with prostate cancer (P = 0.035, Fisher exact test). The clonal cell fraction of normal clones was always higher than the proportion of the prostate estimated as epithelial (P = 5.94 × 10–05, paired Wilcoxon signed rank test) which, along with analysis of primary fibroblasts prepared from BPH specimens, suggests a stromal origin. Constructed phylogenies revealed lineages associated with benign tissue that were completely distinct from adjacent tumour clones, but a common lineage between BPH and non-BPH morphologically normal tissues was often observed. Compared to tumours, normal samples have significantly less single nucleotide variants (P = 3.72 × 10–09, paired Wilcoxon signed rank test), have very few rearrangements and a complete lack of copy number alterations. Conclusions Cells within regions of morphologically normal tissue (both BPH and non-BPH) can expand under selective pressure by mechanisms that are distinct from those occurring in adjacent cancer, but that are allied to the presence of cancer. Expansions, which are probably stromal in origin, are characterised by lack of recurrent driver mutations, by almost complete absence of structural variants/copy number alterations, and mutational processes similar to malignant tissue. Our findings have implications for treatment (focal therapy) and early detection approaches.

Emergency department (ED) use is a concern for surgery patients, physicians and health administrators particularly during a pandemic. The objective of this study was to assess the impact of the pandemic on ED use following cancer-directed surgeries. This is a retrospective cohort study of patients undergoing cancer-directed surgeries comparing ED use from 7 January 2018 to 14 March 2020 (pre-pandemic) and 15 March 2020 to 27 June 2020 (pandemic) in Ontario, Canada. Logistic regression models were used to (1) determine the association between pandemic vs. pre-pandemic periods and the odds of an ED visit within 30 days after discharge from hospital for surgery and (2) to assess the odds of an ED visit being of high acuity (level 1 and 2 as per the Canadian Triage and Acuity Scale). Of our cohort of 499,008 cancer-directed surgeries, 468,879 occurred during the pre-pandemic period and 30,129 occurred during the pandemic period. Even though there was a substantial decrease in the general population ED rates, after covariate adjustment, there was no significant decrease in ED use among surgical patients (OR 1.002, 95% CI 0.957–1.048). However, the adjusted odds of an ED visit being of high acuity was 23% higher among surgeries occurring during the pandemic (OR 1.23, 95% CI 1.14–1.33). Although ED visits in the general population decreased substantially during the pandemic, the rate of ED visits did not decrease among those receiving cancer-directed surgery. Moreover, those presenting in the ED post-operatively during the pandemic had significantly higher levels of acuity.

Background Lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) adolescents and young adults (AYAs) report higher levels of distress than non-LGBTQI AYAs with cancer, and LGBTQI adults with cancer. This mixed methods study examined LGBTQI AYA’s experiences of cancer and cancer care, to understand this distress.Methods Online surveys were completed by 95 LGBTQI AYAs (age 16–39 years); 19 AYAs took part in a one-to-one semi structured interview. Reflexive thematic analysis of interviews and open-ended survey responses facilitated in-depth examination of subjective experiences; descriptive statistics performed on closed-ended survey items identified the percentage of AYAs reporting experiences identified in the qualitative analysis.Results 63% of AYAs reported high or very high distress. Three themes identified in the qualitative analysis included: 1) “Identities in flux”, included subthemes “Cancer disrupts developing identities, and involvement with LGBTQI communities”; “Internalized prejudice impacts identities”; and “Cancer facilitates identities and embodiment”. 2) “Invisibility in cancer care”, included subthemes “Navigating disclosure amongst cis-heteronormative assumptions”, “Discrimination and paternalistic cancer care” and “Cis-heteronormativity within cancer information”. 3) “Precarious social support for LGBTQI AYAs with cancer”, included subthemes “Social support during cancer is helpful for LGBTQI AYAs”, “LGBTQI AYAs navigate limited support”, and “Finding cancer peer support networks is difficult for LGBTQI AYAs”.Conclusions LGBTQI AYAs with cancer experience psychosocial vulnerabilities related to identity development, experiences of care, and social support networks. These factors likely contribute to their previously evidenced elevated risk of distress, relative to both non-LBGTQI AYAs and LGBTQI older adults. AYAs affected by cancer may require additional, tailored supportive care, including targeted information resources, LGBTQI AYA specific cancer support groups, or partnerships and referrals to LGBTQI community organisations. Additionally, it is evident that health care professionals and cancer services have much work to do in ensuring LGBTQI AYAs receive affirming and appropriate care across paediatric and adult clinical settings. They must move beyond assuming all patients are cisgender, heterosexual and do not have intersex variations unless otherwise stated; work to signal inclusivity and facilitate disclosure; and be able to respond appropriately with tailored information and care, which is inclusive of LGBTQI partners, chosen family, and support systems.

BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. FINDINGS: Genetically elevated PUFA desaturase activity was associated (P

Background Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life and there remain no validated predictive models to guide its use. Methods Digital pathology image and clinical data from pre-treatment prostate tissue from 5,727 patients enrolled on five phase III randomized trials treated with radiotherapy +/- ADT were used to develop and validate an artificial intelligence (AI)-derived predictive model to assess ADT benefit with the primary endpoint of distant metastasis. After the model was locked, validation was performed on NRG/RTOG 9408 (n = 1,594) that randomized men to radiotherapy +/- 4 months of ADT. Fine-Gray regression and restricted mean survival times were used to assess the interaction between treatment and predictive model and within predictive model positive and negative subgroup treatment effects. Results In the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis (subdistribution hazard ratio [sHR] = 0.64, 95%CI [0.45–0.90], p = 0.01). The predictive model-treatment interaction was significant (p-interaction = 0.01). In predictive model positive patients (n = 543, 34%), ADT significantly reduced the risk of distant metastasis compared to radiotherapy alone (sHR = 0.34, 95%CI [0.19–0.63], p

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects through a prospective 10-year study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as small clonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of somatic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types,ARID1Amutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical- genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

PURPOSE: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer. METHODS: Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment. RESULTS: The PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent. CONCLUSION: An increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene RAD51C are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. RAD51C promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the RAD51C promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with RAD51C gene silencing and homologous recombination deficiency (HRD). PDX models lost meRAD51C following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of RAD51C was sufficient to drive PARPi resistance. Genomic copy number profiling of one of the PDX models using SNP arrays revealed that this resistance was acquired independently in two genetically distinct lineages.In a cohort of 12 patients with RAD51C-methylated HGSC, various patterns of meRAD51C were associated with genomic “scarring,” indicative of HRD history, but exhibited no clear correlations with clinical outcome. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain meRAD51C after six lines of therapy (four platinum-based), whereas another HGSC sample was found to have heterozygous meRAD51C and elevated RAD51C gene expression (relative to homozygous meRAD51C controls) after only neoadjuvant chemotherapy.As meRAD51C loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy.Significance:Homozygous RAD51C methylation is a positive predictive biomarker for sensitivity to PARP inhibitors, whereas a single unmethylated gene copy is sufficient to confer resistance.

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In dogs, approximately 25–30% of all neoplasms are reported to arise in the skin. The World Health Organization has a detailed histologic classification scheme for mesenchymal and epithelial skin tumors of domestic animals. All skin and subcutaneous masses should have fine needle aspiration cytology performed as part of the diagnostic process before surgical intervention. Appropriate treatment options in an individual case are based on the tumor type and degree of local tumor disease, the results of staging tests, the presence or absence of metastases, and the overall condition of the patient. Surgery can be used as the sole treatment modality or incombination with chemotherapy, radiation therapy, or other adjunctive treatments. The chapter covers mast cell tumors (MCTs) and soft tissue sarcomas. MCTs are the most common malignant cutaneous tumor in dogs and the second most common cutaneous tumor in cats. The treatment of choice for local cutaneous melanoma in both the cat and dog is surgical excision.

The Enhanced Recovery After Surgery (ERAS) care pathways include evidence-based items designed to accelerate recovery after surgery. Interdisciplinarity is one of the key points of ERAS programs.To prepare a consensus document among the members of the Nutrition Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group for Multimodal Rehabilitation (GERM), in which the goal is to homogenize the nutritional and metabolic management of patients included in an ERAS program.69 specialists in Endocrinology and Nutrition and 85 members of the GERM participated in the project. After a literature review, 79 statements were proposed, divided into 5 sections: 17 of general characteristics, 28 referring to the preoperative period, 4 to the intraoperative, 13 to the perioperative and 17 to the postoperative period. The degree of consensus was determined through a Delphi process of 2 circulations that was ratified by a consistency analysis.Overall, in 61 of the 79 statements there was a consistent agreement, with the degree of consensus being greater among members of the SEEN (64/79) than members of the GERM (59/79). Within the 18 statements where a consistent agreement was not reached, we should highlight some important nutritional strategies such as muscle mass assessment, the start of early oral feeding or pharmaconutrition.Consensus was reached on the vast majority of the nutritional measures and care included in ERAS programs. Due to the lack of agreement on certain key points, it is necessary to continue working closely with both societies to improve the recovery of the surgical patients.

È stato implementato un nuovo paradigma sperimentale per verificare l'ipotesi del coinvolgimento del sistema dei neuroni specchio in un compito di previsione dell'esito di un'azione motoria, ossia la traiettoria del pallone in un calcio di rigore. In particolare, è stato messo a punto un compito sperimentale manipolando una serie di filmati di calci di rigore, tirati da calciatori professionisti e ripresi dal punto di vista del portiere, in modo che il video si interrompesse nel momento in cui il piede del calciatore toccava il pallone. Si è ipotizzato che le caratteristiche dei movimenti del calciatore durante la rincorsa forniscano indizi circa la direzione della traiettoria del pallone. Inoltre si è ipotizzato che soggetti con esperienza calcistica interpretino correttamente tali indizi grazie all'attivazione cerebrale delle rappresentazioni motorie dei movimenti che essi utilizzano durante l'esecuzione del calcio di rigore. La prestazione di 20 studenti universitari destrimani nel compito sperimentale sui calci di rigore, valutata in termini di rapidità e accuratezza, è stata messa in relazione con la capacità di rotazione mentale, la reattività di base, l'esperienza calcistica, la familiarità e l'interesse per le partite di calcio. I risultati hanno mostrato che la percentuale di risposte corrette al compito di riconoscimento della traiettoria del pallone è significativamente superiore al caso. Inoltre, si è osservato che l'esperienza calcistica ha un ruolo nel determinare la velocità dei soggetti nel compito sperimentale: i più esperti sono meno impulsivi.&nbsp

Background: The Enhanced Recovery After Surgery (ERAS) care pathways include evidence-based items designed to accelerate recovery after surgery. Interdisciplinarity is one of the key points of ERAS programs. Objective: To prepare a consensus document among the members of the Nutrition Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group for Multimodal Rehabilitation (GERM), in which the goal is to homogenize the nutritional and metabolic management of patients included in an ERAS program. Methods: 69 specialists in Endocrinology and Nutrition and 85 members of the GERM participated in the project. After a literature review, 79 statements were proposed, divided into 5 sections: 17 of general characteristics, 28 referring to the preoperative period, 4 to the intraoperative, 13 to the perioperative and 17 to the postoperative period. The degree of consensus was determined through a Delphi process of 2 circulations that was ratified by a consistency analysis. Results: Overall, in 61 of the 79 statements there was a consistent agreement, with the degree of consensus being greater among members of the SEEN (64/79) than members of the GERM (59/79). Within the 18 statements where a consistent agreement was not reached, we should highlight some important nutritional strategies such as muscle mass assessment, the start of early oral feeding or pharmaconutrition. Conclusion: Consensus was reached on the vast majority of the nutritional measures and care included in ERAS programs. Due to the lack of agreement on certain key points, it is necessary to continue working closely with both societies to improve the recovery of the surgical patients.

In embryos of most animal species, the zygotic centrosome is assembled by the centriole derived from the sperm cell and pericentriolar proteins present in the oocyte. This zygotic centrosome acts as a microtubule organizing center (MTOC) to assemble the sperm aster and mitotic spindle. As MTOC formation has been studied mainly in adult cells, very little is known about the formation of the zygotic MTOC. Here, we show that zebrafish (Danio rerio) embryos lacking either maternal or paternal Cfap53, a centriolar satellite protein, arrest during the first cell cycle. Although Cfap53 is dispensable for sperm aster function, it aids proper formation of the mitotic spindle. During cell division, Cfap53 colocalizes with γ-tubulin and with other centrosomal and centriolar satellite proteins at the MTOC. Furthermore, we find that γ-tubulin localization at the MTOC is impaired in the absence of Cfap53. Based on these results, we propose a model in which Cfap53 deposited in the oocyte and the sperm participates in the organization of the zygotic MTOC to allow mitotic spindle formation.

Growth hormone (GH) and insulin‐like growth factor‐1 (IGF1) play an important role in mammalian development, cell proliferation and lifespan. Especially in cases of tumor growth there is an urgent need to control the GH/IGF1 axis. In this study we screened a 38,480-compound library, and in two consecutive rounds of analogues selection, we identified active lead compounds based on the following criteria: inhibition the GH receptor (GHR) activity and its downstream effectors Jak2 and STAT5, and inhibition of growth of breast and colon cancer cells. The most active small molecule (BM001) inhibited both the GH/IGF1 axis and cell proliferation with an IC50 of 10‐30 nM of human cancer cells. BM001 depleted GHR in human lymphoblasts. In preclinical xenografted experiments, BM001 showed a strong decrease in tumor volume in mice transplanted with MDA‐MB‐231 breast cancer cells. Mechanistically, the drug acts on the synthesis of the GHR. Our findings open the possibility to inhibit the GH/IGF1 axis with a small molecule.

This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly in clinically ill cats, evaluating the final established diagnosis, describe adrenal ultrasound findings and if the adrenomegaly was suspected or incidental. Abdominal ultrasonography reports of cats presenting to a veterinary teaching hospital between October 2018 and February 2021 were retrospectively reviewed. Cats showing adrenomegaly (one or both glands having a dorsoventral axis >4.8 mm) were selected and medical records respectively evaluated. Nine-hundred and eighty-three ultrasonographical reports were selected, of which, 68 (7%) disclosed adrenomegaly. European/Domestic Short-Hair (62/68; 91%) male (44/68; 65%) castrated (35/44; 80%) cats were overrepresented. Adrenomegaly was an incidental finding in 62/68 (91%) cats while in 6/68 (9%) it was identified in the context of investigating a potential adrenal disease. Concerning established diagnosis, chronic kidney disease was overrepresented (25/68; 37%), followed by endocrinopathies (20/68; 29%). Adrenomegaly was bilateral in 53% (36/68) of cases. In unilateral cases (32/68; 47%), it was more prevalent on the left side (23/32; 72%), with a normal-sized contralateral adrenal gland. Left adrenal demonstrated a larger size and a tendency to oval shape. This study assesses the prevalence of adrenomegaly in clinically ill cats, reinforcing it can be an incidental ultrasound finding. info:eu-repo/semantics/publishedVersion

Early cervical cancer; Fertility-sparing surgery; Radical hysterectomy Cáncer de cuello uterino temprano; Cirugía conservadora de la fertilidad; Histerectomía radical Càncer de coll uterí precoç; Cirurgia conservadora de la fertilitat; Histerectomia radical Objective: Fertility-sparing surgery (FSS) is the treatment of choice for patients with early cervical cancer (ECC) and fertility desire, but survival rates compared to radical hysterectomy (RH) have been scarcely reported. The aim of this study was to analyse the oncological outcomes of FSS compared to a balanced group of standard RH. Methods: A retrospective multicentre study of ECC patients who underwent FSS or RH was carried out in 12 tertiary hospitals in Spain between January 2005 and January 2019. The experimental group included patients who underwent a simple and radical trachelectomy, and the control group included patients who underwent RH. Optimal 1:1 propensity score (PS) matching analysis was performed to balance the series. Results: The study included 222 patients with ECC; 111 (50%) were treated with FSS, and 111 (50%) were treated with RH. After PS matching, a total of 38 patients in the FSS group and 38 patients in the RH group were analysed. In both groups, the overall survival (HR 2.5; CI 0.89, 7.41) and recurrence rates (28.9% in the FSS group vs. 13.2% in RH group) were similar. The rate of disease-free survival at 5 years was 68.99% in the FSS group and 88.01% in the RH group (difference of −19.02 percentage points; 95% CI −32.08 to −5.96 for noninferiority). In the univariate analysis, only tumour size reached statistical significance. Conclusion: FSS offers excellent disease-free and overall survival in women with ECC with fertility desire and is not inferior compared to RH. This work received financial support from the Medtronic University Chair for Training and Surgical Research, University Jaume I (UJI), Castellon, Spain.

Biosimilars are biologic products that are highly similar to a licensed reference biologic, with no clinically meaningful differences in quality characteristics, biological activity, safety, or efficacy. Biosimilars can help to fulfill unmet medical needs due to their cost effectiveness while at the same time being as efficacious as the innovator drug. They can also improve patient access to otherwise costly innovator biologics. India has the largest number of approved biosimilars as compared to the US and Europe. However, the numbers of clinical studies that are conducted to prove the biosimilarity are lesser than the number of biosimilars approved, which is evident by the number of CTRI registrations done. Some studies have shown the quality of biosimilars approved and marketed in India to be inferior to the innovator drug. This raises concerns regarding the quality of the biosimilars. In this review, the similarities and differences in the guidelines, the approval process, and quality enforcement measures prevailing in the three regulatory regions of USA, Europe and India are discussed. Changes in the approval process and post approval monitoring of drugs and manufacturing facilities are recommended in order to ensure sustained quality standards of drugs entering the market.

Purpose: Prostate cancer (PCa) is highly heritable. No validated PCa risk model currently exists. We therefore sought to develop a genetic risk model that can provide personalised predicted PCa risks based on known moderate-to-high-risk pathogenic variants, low-risk common genetic variants and explicit cancer family history, and to externally validate the model in an independent prospective cohort. Patients and methods: We developed a risk model using a kin-cohort comprising individuals from 16,633 PCa families ascertained in the UK in 1993-2017 from the UK Genetic Prostate Cancer Study, and complex segregation analysis adjusting for ascertainment. The model was externally validated in 170,850 unaffected men (7,624 incident PCas) recruited in 2006-2010 to the independent UK Biobank prospective cohort study. Results: The most parsimonious model included the effects of pathogenic variants in BRCA2, HOXB13 and BRCA1 and a polygenic score based on 268 common low-risk variants. Residual familial risk was modelled by a hypothetical recessively inherited variant and a polygenic component whose standard deviation decreased log-linearly with age. The model predicted familial risks that were consistent with those reported in previous observational studies. In the validation cohort, the model discriminated well between unaffected men and men with incident PCas within 5yr (C-index=0.790, 95% CI 0.783-0.797) and 10yr (C-index=0.772, 95% CI 0.768-0.777). The 50% of men with highest predicted risks captured 86.3% of PCa cases within 10yr. Conclusion: This is the first validated risk model offering personalised PCa risks. The model will assist in counselling men concerned about their risk and can facilitate future risk-stratified population screening approaches.

PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

Introduction. In the Philippines, lung, breast, colon-rectum, and oral cavity cancers are among the top 10 most common cancers. This study evaluates the risk factors for these cancers among Filipinos. Methods. This age-matched case-control study included incident primary cancers (histologically-diagnosed) of the lung, breast (also matched for sex), colon-rectum and oral cavity. Controls(clinically free and no history of cancer) were obtained from the same tertiary hospitals as the cases. Target sample size was 283 cases and 283 controls per cancer type. Conditional logistic regression was done. Results. Exposure to cigarette/tobacco was a significant risk factor for lung (OR of current smoker compared to non-smoker [95% Confidence Interval]: 3.6 [1.6-7.9]) and oral cavity cancers (2.0 [1.2-3.3]); family history (1st degree) for lung (4.3 [1.3 – 14.2]) and breast cancers (3.0 [1.2-7.5]); every year increase in age at first pregnancy for breast cancer (1.06 [1.02-1.11]). Other risk factors for oral cavitywere passive smoking (2.8 [1.6-5.1]), chewing tobacco (5.2[1.4-19.5]) and inverted cigarette smoking (3.2[1.3-8.1]). Fish sauce (patis) was found to be a protective factor for breast cancer (0.34 [0.22-0.51]) and oral cavity (0.44 [0.25-0.78]) and use of shrimp paste (bagoong) (0.48 [0.27-0.84]) for oral cavity. Conclusion and Recommendations. Except for family history of cancer, the identified risk factors for lung, colon-rectum, and oral cavity cancers are preventable. Proper diet and lifestyle, avoidanceof cigarettes and tobacco, and environmental safety in the workplace are key cancer prevention measures. Public awareness campaign and continuing healthcare provider education must always be part of a cancer prevention program.

En el momento en el que se plantea a un paciente la necesidad de un procedimiento quirúrgico, este inicia una respuesta fisiológica de estrés denominado “estrés perioperatorio” que se prolongará en el tiempo hasta la completa recuperación. Este estrés perioperatorio, implica una serie de cambios hormonales, metabólicos y tisulares que tienen efectos endocrinos, hematológicos e inmunológicos como: activación de sistema simpático, resistencia a la insulina, secreción hipofisaria de hormonas contrainsulares, producción de citocinas y prostaglandinas, activación del complemento, liberación de reactantes de fase aguda, leucocitosis/leucopenia y alteraciones endoteliales protrombóticas1. Los programas de recuperación intensificada, tienen como objetivo, desde un punto de vista multidisciplinar y apoyándose en la evidencia disponible, disminuir el estrés quirúrgico que conlleva la aparición de disfunción orgánica. Desde el año 2007, un grupo comprometido de especialistas en Cirugía General de nuestro país, se propuso modificar las prácticas inseguras para acometer sus procesos quirúrgicos desde la perspectiva del “primun non nocere”, rompiendo con mitos de manejo preestablecidos sin evidencia demostrada. A este Grupo se asociaron otros profesionales de la sanidad como Anestesiólogos, Cirujanos de otras especialidades, Enfermeras, Cardiólogos, Neumólogos, endocrinólogos/Nutricionistas, Hematólogos, Rehabilitadores, y todos conformaron el Grupo Español de Rehabilitación Multimodal —GERM— cuyo propósito es el promover una práctica clínica perioperatoria segura y avalada por la Medicina Basada en la Evidencia para lograr una recuperación postoperatoria rápida de los pacientes. El Grupo GERM, como sociedad científica sin ánimo de lucro, tiene entre sus funciones la de difundir e implantar la investigación amparada en la Medicina Basada en la Evidencia y propone el desarrollo de programas que garanticen la práctica clínica óptima y más segura en el ámbito quirúrgico, la disminución de la variabilidad perioperatoria tanto diagnóstica como terapéutica, así como la consecución de la eficiencia. Fruto de los trabajos realizados por el GERM, se publicó en 2015 la Vía Clínica de Recuperación Intensificada en Cirugía Abdominal (RICA), al amparo del Ministerio de Sanidad, Seguridad Social e Igualdad y el Instituto Aragonés de Ciencias de la Salud, y auditada por Guía-Salud. Contemplaba 95 ítems de práctica clínica con sus niveles de evidencia y grados de recomendación según el sistema GRADE teniendo como alcance la cirugía abdominal del adulto. Esta Vía RICA se ha actualizado en 2021 y en la actualización las especialidades quirúrgicas a las que se dirigen las recomendaciones han aumentado hasta alcanzar a la práctica totalidad de los procedimientos (denominándose Vía Clínica de Recuperación Intensificada en Cirugía del Adulto), de tal manera que en estos momentos se cuenta con unos protocolos de actuación basados en la mejor evidencia disponible, debidamente actualizados, para el 90% de la cirugía programada que se hace en este país. A través del proyecto IMPRICA que comenzó en 2017 y se mantiene activo, se pretende hacer extensivo a los hospitales españoles la aplicación e implementación de los Programas que dimanan de la Vía Clínica mediante información y formación de equipos multidisciplinares de trabajo, investigación previa y posterior a la implantación de la misma y, comparación y análisis de los resultados obtenidos tras él. En este sentido, y gracias a esta iniciativa los protocolos de recuperación intensificada se aplican de manera rutinaria en más de 50 centros de nuestro país. En 2019 el grupo GERM publicó el estudio POWER 13, un estudio de cohortes con una muestra de 2084 pacientes adultos de 80 hospitales, destacando que un aumento en el cumplimiento de las recomendaciones de los protocolos RICA se asociaba a una disminución de las complicaciones postoperatorias, pero aun así las complicaciones posoperatorias fueron frecuentes en cirugía colorrectal, con tasas de complicaciones moderadas y severas del 27.9%. Un hecho similar se demostró también con el estudio POWER 24, en cirugía ortopédica. En cualquier caso, la utilidad de estos estudios no sólo fue para cuantificar las complicaciones sino también conocer cuáles eran y su relación con mortalidad, estancia hospitalaria y eficiencia. Un aspecto de especial relevancia es conocer el manejo de dichas complicaciones. En este punto quedó patente que no existe un patrón común y el paciente complicado sigue en la mayoría de los casos los pasos de los cuidados tradicionales, es decir abandona la vía RICA y, con ello, la seguridad y calidad asistencial que ofrece la misma, volviendo a la heterogeneidad del manejo y perdiendo las iniciativas adoptadas hasta el momento de la detección de la complicación. Es muy importante, además, insistir en que, si bien reducir las complicaciones y la mortalidad precoz después de la cirugía es clave, no lo es menos manejar adecuadamente las complicaciones. En este sentido, numerosos estudios muestran que el exceso de mortalidad hospitalaria, no se relaciona tanto con las tasas de complicaciones, sino con la manera de rescatar a los pacientes de las complicaciones más comunes. Es por ello por lo que estamos de acuerdo con quienes piensan que la investigación clínica en el paciente quirúrgico debe centrarse no sólo en la caracterización detallada de los cuidados perioperatorios y en la implementación de estos protocolos para reducir las tasas de complicaciones sino también en establecer estrategias comunes para manejar a los pacientes de las complicaciones cuando ocurren

The Infierno glacier is located in Aragon (Spain), Pyrenees mountain range, southern slope, the only one in this country that still preserves white glaciers. These are the southernmost glaciers in Europe and are currently in rapid regression. The work analyzes the evolution of the glacier between 2016 and 2022 (taking as "year zero" or starting point, 2015). In addition to the observations on the glacier itself, the variables (precipitation, temperatures, snow volumes and thicknesses) that allow understanding this evolution are studied. The results offer strong regression, with thickness losses in that period of 4.6 m and retreat of its front of 14.9 m. The evolution has frequent trend changes, linked to the interannual climatic irregularity characteristic of this mountain range. The main explanatory factor is the thermal increase. The thermal anomalies with respect to the average reference values have increased, in this period, +0.55° C. The year 2022 has been particularly warm and has recorded the greatest regression of the glacier (between May and August, the thermal anomalies were between +4° C and +2° C). Regarding precipitations, they have irregular tendencies and show a decreasing trend (-9% in the same period of time).

International audience; This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.

Key Points Question What breast tumor characteristics are associated with rare pathogenic protein truncating or missense variants in breast cancer susceptibility genes? Findings In this case-control study involving 46 387 control participants and 42 680 women with a diagnosis of breast cancer, pathology features (eg, tumor subtype, morphology, size, TNM stage, and lymph node involvement) associated with rare germline (likely) pathogenic variants in 9 different breast cancer susceptibility genes were studied. Substantial differences in tumor subtype distribution by gene were found. Meaning The results of this study suggest that tumor subtypes differ by gene; these findings can potentially inform guidelines for gene panel testing, risk prediction in unaffected individuals, variant classification, and understanding of breast cancer etiology., Importance Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction. Objective To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies. Design, Setting, and Participants The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021. Exposures Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53. Main Outcomes and Measures The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes. Results The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2− high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ERBB2+ and HR–ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger. Conclusions and Relevance The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies., This case-control study examines tumors associated with breast cancer susceptibility genes in large-scale population- or hospital-based studies.

Objective: To study the behaviour of Lumbar Lordosis (LL) after non-instrumented decompression surgery in patients diagnosed with Lumbar Spinal Stenosis (LSS). Methods and materials: Retrospective analysis of patients undergoing non-lumbar instrumented decompression surgery for lumbar spine stenosis, operated on between January 2011 and December 2017. The variables collected were age, sex, affected segment, and presence or not of degenerative spondylolisthesis (ELS). The Lumbar Lordosis (LL) parameter was analysed using conventional radiology in standing position pre and postoperatively. Results: 64 patients were selected, 17 women and 47 men, with an average age of 68 (35-83). 65% stenosis was located in a single level, and 39.1% had degenerative ELS grade I. The average follow-up was 26 months (6m-104m). A preoperative LL angle of 43.2º (9.8º-70.8º) and 47º (8º-76º) were found at the postoperative follow-up, with an average difference of 3.8º (-15.7º-20.2º). 9.4% (6 patients) of degenerative ELS evolved to grade II, and 8 patients needed reoperation for different reasons. In patients with ELS, we found a greater increase in postoperative LL (5.59º) than in patients without ELS (2.61º) (p = 0.08). No statistically significant relationship was found between the behaviour of the LL with the number of decompressed levels (p = 0.43) and the need for reoperation (p = 0.26). Conclusions: According to our study, the technique of posterior decompression without instrumentation of the lumbar spine stenosis is not associated with a decrease of lumbar lordosis parameter. Conversely, there is a slight tendency for LL to increase in cases where a degenerative ELS is present.