Prognostic value of HER2DX in early-stage HER2-positive breast cancer: a comprehensive analysis of 757 patients in the Sweden Cancerome Analysis Network-Breast dataset (SCAN-B).

BACKGROUND: The HER2DX risk-score has undergone rigorous validation in prior investigations involving patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer. In this study, we present the outcomes of the HER2DX risk-score within the most recent release of the Sweden Cancerome Analysis Network-Breast (SCAN-B) HER2+ cohort. This updated examination benefits from a larger patient sample, an extended follow-up duration, and detailed treatment information. MATERIALS AND METHODS: Clinical and RNAseq data from the SCAN-B dataset were retrieved from Gene Expression Omnibus (GSE81538). Among the 6600 patients, 819 had HER2+ breast cancer, with 757 individuals with research-based HER2DX risk-scores and corresponding survival outcomes. The HER2DX risk-score was evaluated (i) as a continuous variable and (ii) using predefined cut-offs. The primary endpoint for this study was overall survival (OS). The Kaplan-Meier method and Cox models were used to estimate OS and a multistate model with four states was fitted to better characterize patients' follow-up. RESULTS: The median follow-up time was 7.5 years (n = 757). The most common systemic therapy was chemotherapy with trastuzumab (82.0%) and most tumors were classified as T1-T2 (97.1%). The HER2DX risk-score as a continuous variable was significantly associated with OS after adjustment for clinical variables and treatment regimen [hazard ratios (HR) per 10-unit increment = 1.31, 95% confidence interval (CI) 1.13-1.51, P < 0.001] as well as within predefined risk groups (high versus low; HR = 2.57, 95% CI 1.36-4.85, P < 0.001). Patients classified as HER2DX high-risk also had higher risk of (i) breast cancer recurrence and (ii) death without previous recurrence. Within the subgroup of HER2+ T1N0 tumors (n = 297), those classified as high-risk demonstrated inferior OS compared to low-risk tumors (7-year OS 77.8% versus 96.8%, P < 0.001). The HER2DX mRNA ERBB2 score was associated with clinical HER2 status (area under the receiver operating characteristic curve = 0.91). CONCLUSIONS: In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinicopathological variables, including treatment regimen with or without trastuzumab.

Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

Family burden after critical illness: the forgotten caregivers / La sobrecarga familiar tras una enfermedad crítica: los cuidadores olvidados

Objective To determine the incidence of primary caregiver burden in a cohort of family members of critically ill patients admitted to ICU and to identify risk factors related to its development in both the patient and the family member. Design Prospective observational cohort study was conducted for 24 months. Setting Hospital Universitario Clínico San Cecilio, Granada. Patients The sample was the primary caregivers of all patients with risk factors for development of PICS (Post-Intensive Care Syndrome). Interventions The follow-up protocol consisted of evaluation 3 months after discharge from the ICU in a specific consultation. Main variables of interest The scales used in patients were Barthel, SF-12, HADS, Pfeiffer, IES-6 and in relatives the Apgar and Zarit. Results A total of 93 patients and caregivers were included in the follow-up. 15 relatives did not complete the follow-up questionnaires and were excluded from the study. The incidence of PICS-F (Family Post Intensive Care Syndrome) defined by the presence of primary caregiver burden in our cohort of patients is 34.6% (n=27), 95% CI 25.0−45.7. The risk factors for the development of caregiver burden are the presence of physical impairment, anxiety or post-traumatic stress in the patient, with no relationship found with the characteristics studied in the family member. Conclusions One out of 3 relatives of patients with risk factors for the development of PICS presents at 3 months caregiver burden. This is related to factors dependent on the patient's state of health. (AU)

Objetivo Determinar la incidencia de la sobrecarga del cuidador principal en una cohorte de familiares de pacientes críticos ingresados en UCI e identificar los factores de riesgo relacionados con su desarrollo tanto en el paciente como en el familiar. Diseño Estudio de cohortes observacional prospectivo durante 24 meses. Ámbito Hospital Universitario Clínico San Cecilio de Granada. Pacientes La muestra estuvo compuesta por los cuidadores principales de todos los pacientes con factores de riesgo para el desarrollo de SPCI (Síndrome Post-Cuidados Intensivos). Intervenciones El protocolo de seguimiento consistió en la evaluación a los 3 meses del alta de la UCI en una consulta específica. Variables de interés principales Las escalas utilizadas fueron Barthel, SF-12, HADS, Pfeiffer, IES-6, Apgar y Zarit. Resultados Un total de 93 pacientes y cuidadores fueron incluidos en el seguimiento. 15 cuidadores no completaron los cuestionarios de seguimiento y fueron excluidos del estudio. La incidencia de PICS-F (Síndrome Post-Cuidados Intensivos Familiar) definido por la presencia de sobrecarga del cuidador en nuestra cohorte es del 34,6% (n=27), IC 95% 25,0–45,7. Los factores de riesgo para el desarrollo del mismo son la presencia de deterioro físico, ansiedad o estrés postraumático en el paciente, no encontrándose relación con las características estudiadas en el familiar. Conclusiones Uno de cada 3 familiares de pacientes con factores de riesgo para el desarrollo de SPCI presenta a los 3 meses sobrecarga del cuidador, relacionándose con factores dependientes del estado de salud del paciente. (AU)

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Family burden after critical illness: the forgotten caregivers.

OBJECTIVE: To determine the incidence of primary caregiver burden in a cohort of family members of critically ill patients admitted to ICU and to identify risk factors related to its development in both the patient and the family member. DESIGN: Prospective observational cohort study was conducted for 24 months. SETTING: Hospital Universitario Clínico San Cecilio, Granada. PATIENTS: The sample was the primary caregivers of all patients with risk factors for development of PICS (Post-Intensive Care Syndrome). INTERVENTIONS: The follow-up protocol consisted of evaluation 3 months after discharge from the ICU in a specific consultation. MAIN VARIABLES OF INTEREST: The scales used in patients were Barthel, SF-12, HADS, Pfeiffer, IES-6 and in relatives the Apgar and Zarit. RESULTS: A total of 93 patients and caregivers were included in the follow-up. 15 relatives did not complete the follow-up questionnaires and were excluded from the study. The incidence of PICS-F (Family Post Intensive Care Syndrome) defined by the presence of primary caregiver burden in our cohort of patients is 34.6% (n=27), 95% CI 25.0-45.7. The risk factors for the development of caregiver burden are the presence of physical impairment, anxiety or post-traumatic stress in the patient, with no relationship found with the characteristics studied in the family member. CONCLUSIONS: One out of 3 relatives of patients with risk factors for the development of PICS presents at 3 months caregiver burden. This is related to factors dependent on the patient's state of health.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

Implementing an outpatient surgical management in moderated-high risk patients with groin hernia repair.

PURPOSE: There is a growing trend to expand Ambulatory Surgery (AS) criteria in abdominal wall surgery. No Admission (NOADS) circuit. The present study aimed to assess the impact of classification criteria on postoperative results and hospital stays in a NOADS versus a conventional admission circuit to throw some light on surgical circuit inclusion. METHODS: A retrospective analysis of a prospective;y maintained database was performed comparing groin hernia's interventions in a NOADS vs Admission circuit in our center in 2018-2021. A multiple regression predictive model followed by a retrospective retest were dessigned to assess the impact of each criterion on hospital stay. In total, 743 patients were included, 399 in the Admission circuit (ADC) and 344 in NOADS circuit (NOADS). RESULTS: There were no statistical differences in complication or readmission rates (p = 0.343 and p = 0.563), nevertheless, a shorter hospital stay was observed in NOADS (p = 0.000). A hierarchical multiple regression predictive model proposed two opposite scenarios. The best scenario, not likely to need admission, was a female patient operated via the laparoscopic approach of a unilateral primary hernia (Estimated Postoperative Stay: 0.049 days). The worst scenario, likely to need admission, was a male patient operated via the open approach of a bilateral and recurrent hernia (Estimated Postoperative Stay: 1.505 Days). CONCLUSION: Groin hernia patients could safely benefit from a No Admission (NOADS) circuit. Our model could be useful for surgical circuit decision-making, especially for best/worst scenarios.

Achilles enthesitis on physical examination leads to worse outcomes after 2 years of follow up in patients with ankylosing spondylitis from REGISPONSER-AS registry.

BACKGROUND: Enthesitis represents one of the most important peripheral musculoskeletal manifestations in patients with axial spondyloarthritis (axSpA). However, studies specifically evaluating Achilles tendon enthesitis and its impact over time are scarce. The objectives of this study were to evaluate the impact of Achilles' tendon enthesitis found at baseline during physical examination on the outcome measures after 2 years of follow-up in patients with ankylosing spondylitis (AS). METHODS: This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. Linear regression models adjusted for age, body mass index (BMI), and anti-TNF intake were conducted to evaluate the association between the presence of Achilles enthesitis at baseline and the patient-reported outcome (PRO) scores at baseline. The impact of this feature on PROs over 2 years of follow-up was evaluated using mixed models for repeated measures adjusted for age, BMI, and anti-TNF intake. RESULTS: Among the 749 patients included, 46 patients (6.1%) showed Achilles' tendon enthesitis during physical examination at the baseline study visit. Patients with Achilles enthesitis had an increase in the global VAS score, BASDAI, mBASDAI, ASDAS-CRP, and BASFI scores in comparison with patients without this feature. In addition, the mean global VAS, BASDAI, and ASDAS-CRP scores were significantly higher among patients with Achilles enthesitis over the 2 years of follow-up after adjusting for age, BMI, and current anti-TNF intake. The percentage of patients achieving ASDAS low disease activity (ASDAS < 2.1) after 2 years of follow-up was 15.9% and 31.5% for patients with and without Achilles enthesitis, respectively (p = 0.030). CONCLUSIONS: In patients with AS, the presence of Achilles' tendon enthesitis was associated with worse scores on the outcome measures after 2 years of follow-up, leading to a lower probability of achieving low disease activity.

Splicing machinery is profoundly altered in systemic lupus erythematosus and antiphospholipid syndrome and directly linked to key clinical features.

OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.

Female sex workers and police violence during the Covid-19 health crisis in 2020-2021: results from the EPIC multi-country community-based research program in Argentina.

BACKGROUND: Female sex workers (FSW) have been disproportionately impacted by the Covid-19 crisis. Data show increases of police violence toward key populations (KP), likely a consequence of their role in enforcing health government measures. This study aimed to identify factors associated with police violence experienced by FSW during the Covid-19 crisis in Argentina. METHODS: EPIC is a multi-country, cross-sectional, community-based research program evaluating the impact of Covid-19 among KP. In Argentina, the study was conducted in collaboration with FSW community-based organizations (CBO). Participants completed an online survey (October 2020-April 2021). Police violence was measured as having experienced episodes of violence (physical, verbal, psychological or sexual) by security forces since the start of the health crisis. Factors associated with police violence were assessed in logistic regression models. RESULTS: Among 173 respondents, median age was 34 [IQR 27-42], 39.3% were transgender women (TW), 78.1% declared sex work as their only income and 71.7% mentioned their financial situation has deteriorated with the health crisis. Nearly half of FSW (44.5%) reported experiencing police violence within the first year of the Covid-19 pandemic, and among them, 76.6% declared more frequent violence episodes since the beginning of the health crisis. After adjustment for age, being a TW (aOR [95% CI] = 2.71 [1.21;6.05]), reporting non-injection drug use (2.92 [1.02;8.36]), having a considerably deteriorated financial situation (3.67 [1.47;9.21]), having had a consultation with a CBO worker for medical care/treatments (5.56 [2.15;14.37]) and declaring fear or experiences of discrimination by physicians/other health workers (2.97 [1.21;7.29]), since the beginning of the Covid-19 health crisis, were independently associated with police violence. CONCLUSIONS: FSW in Argentina have experienced an increase in police violence since the beginning of the health crisis. Belonging to multiple KP (FSW, TW, people who use drugs) increases the likelihood of experiencing police violence, highlighting the need of an intersectional approach to develop interventions to reduce stigma and violence against FSW. CBOs have provided essential support and services during the crisis to FSWs, and other KPs, who may have avoided traditional healthcare structures due to fear or experiences of discrimination.

Adherence to a gluten-free diet in celiac disease patients from Paraguay.

INTRODUCTION AND AIM: The treatment for celiac disease is a gluten-free diet that should be strictly and permanently carried out. Our aims were to determine adherence to the gluten-free diet and the risk factors for non-adherence. MATERIALS AND METHODS: An observational, cross-sectional, comparative study was conducted. It included individuals of both sexes and of any age that presented with celiac disease, lived in Paraguay from January to April 2021, and agreed to participate in the survey. Incomplete questionnaires were excluded. Non-probabilistic convenience sampling was utilized. Adherence was measured using the Leffler questionnaire. The study was approved by the Ethics Committee of the Universidad Privada del Este. RESULTS: The sample consisted of 371 respondents, 322 (87%) of whom were adults, with a mean age of 38 ±â€¯12 years, and 49 (13%) of whom were children and adolescents, with a mean age of 10 ±â€¯5 years. Female sex was predominant (85%). Adherence to the gluten-free diet was detected in 59% of the adults and 73% of the children and adolescents. The factors significantly associated with adherence included belonging to the child and adolescent age group and having had the diagnosis for a longer time: 9 ±â€¯8 years for the adherence group and 7 ±â€¯8 years for the non-adherence group. CONCLUSIONS: The present study demonstrated the frequency of adherence to the gluten-free diet in celiac patients in Paraguay. Psychologic and nutritional support is recommended for individuals with celiac disease that do not adhere to their treatment.

Comparison of magnetic resonance angiography techniques to brain digital subtraction arteriography in the setting of mechanical thrombectomy: A non-inferiority study.

INTRODUCTION: We performed a non-inferiority study comparing magnetic resonance angiography (MRA) techniques including contrast-enhanced (CE) and time-of-flight (TOF) with brain digital subtraction arteriography (DSA) in localizing occlusion sites in acute ischemic stroke (AIS) with a prespecified inferiority margin taking into account thrombus migration. MATERIALS AND METHODS: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes large-vessel-occlusion (LVO) AIS treated with mechanical thrombectomy (MT) following brain magnetic resonance imaging (MRI) including both CE-MRA and TOF-MRA. Locations of arterial occlusions were assessed independently for both MRA techniques and compared to brain DSA findings. Number of patients needed was 48 patients to exclude a difference of more than 20%. Discrepancy factors were assessed using univariate general linear models analysis. RESULTS: The study included 151 patients with a mean age of 67.6±15.9years. In all included patients, TOF-MRA and CE-MRA detected arterial occlusions, which were confirmed by brain DSA. For CE-MRA, 38 (25.17%) patients had discordant findings compared with brain DSA and 50 patients (33.11%) with TOF-MRA. The discordance factors were identical for both MRA techniques namely, tandem occlusions (OR=1.29, P=0.004 for CE-MRA and OR=1.61, P<0.001 for TOF-MRA), proximal internal carotid artery occlusions (OR=1.30, P=0.002 for CE-MRA and OR=1.47, P<0.001 for TOF-MRA) and time from MRI to MT (OR=1.01, P=0.01 for CE-MRA and OR=1.01, P=0.02 for TOF-MRA). CONCLUSION: Both MRA techniques are inferior to brain DSA in localizing arterial occlusions in LVO-AIS patients despite addressing the migratory nature of the thrombus.

Caracterización epidemiológica: análisis de tasa de mortalidad e índice de swaroop para peritonitis en el periodo 2017- 2021, en Chile / Epidemiological characterization: peritonitis mortality rate and swaroop Index in the period 2017 - 2021, in Chile

Introducción: La peritonitis alcanza una mortalidad global de hasta un 60%. Dada la falta de estudios epidemiológicos nacionales, se plantea calcular la tasa de mortalidad (TM) por peritonitis entre los años 2017-2021 en Chile. Metodología: Estudio descriptivo, ecológico, sobre defunciones por peritonitis entre los años 2017-2021 en Chile (N=1.741), en población mayor de 15 años según grupo etario, sexo y región con datos obtenidos del departamento de estadística e información en salud. Se utilizó estadística descriptiva, cálculo de TM e índice de Swaroop (IS). No requirió aprobación por comité de ética. Resultados: Se calculó una TM de 2,47/100.000 habitantes entre los años 2017 y 2021, siendo el año 2020 la mayor con 3,07. El sexo femenino presentó una tasa de 2,65. El grupo etario con mayor TM es el de 80 y más con 141,7/100.000 habitantes. Para el IS por región, lideran las regiones XV y XII con 100%, siendo la más baja la XI con 83,3%. Discusión: El pico de TM para el año 2020 coincide con la pandemia por Covid-19, donde se reporta mayor mortalidad postoperatoria en pacientes infectados. El IS se mantiene mayor al 90% en el país, excepto en las Regiones X y XI, probablemente debido a la menor disponibilidad de centros de alta complejidad. Conclusión: Dada la ausencia de datos recientes de mortalidad para peritonitis, se realizó una actualización epidemiológica local, con perspectiva comparativa regional respecto a las TM de la población general y en mayores de 50 años.

Introduction: Peritonitis reaches an overall mortality of up to 60%. Given the lack of national epidemiological studies, it is proposed to calculate the mortality rate (MR) due to peritonitis between the years 2017-2021 in Chile. Methodology: Descriptive, ecological study about deaths by peritonitis between 2017 and 2021 in Chile (N=1,741), in a population older than 15 years old according to age group, sex, and region with data obtained from Departamento de Estadística e Información en Salud. Descriptive statistics were used, MR calculation, and Swaroop Index (SI). It did not require approval by an ethics committee. Results: A MR of 2.47/100,000 was calculated between the years 2017 and 2021, with 2020 being the highest with 3.07. The female sex presented a rate of 2.65. The age group with the highest MR is 80 and over with 141.7/100,000. For the SI by region, the XV and XII regions lead with 100%, the lowest being XI region with 83.3%. Discussion: The peak of MR for the year 2020 coincides with the Covid-19 pandemic and the highest postoperative mortality in infected patients. The SI remains above 90% in the country, except in X and XI regions, probably due to the lower availability of high complexity centers. Conclusion: Given the lack of recent mortality data for peritonitis, a local epidemiological update was carried out, with a regional comparative perspective regarding MR in the general population and in those over 50 years old.

Anti-dsDNA Antibodies Increase the Cardiovascular Risk in Systemic Lupus Erythematosus Promoting a Distinctive Immune and Vascular Activation.

Objective: Systemic lupus erythematosus (SLE) is associated to boosted atherosclerosis development and a higher cardiovascular disease risk. This study aimed to delineate the role of anti-double stranded DNA (anti-dsDNA) antibodies on the molecular profile and the activity of immune and vascular cells, as well as on their enhanced cardiovascular risk. Approach and Results: Eighty SLE patients were included. Extensive clinical/analytical evaluation was performed, including cardiovascular disease parameters (endothelial function, proatherogenic dyslipidemia, and carotid intima-media thickness). Gene and protein expression profiles were evaluated in monocytes from patients diagnosed positive or negative for anti-dsDNA antibodies by using NanoString and cytokine arrays, respectively. NETosis and circulating inflammatory profile was assessed in both neutrophils and plasma. Positivity and persistence of anti-dsDNA antibodies in SLE patients were associated to endothelial dysfunction, proatherogenic dyslipidemia, and accelerated atherosclerosis. In parallel, anti-dsDNA antibodies were linked to the aberrant activation of innate immune cells, so that anti-dsDNA(+) SLE monocytes showed distinctive gene and protein expression/activity profiles, and neutrophils were more prone to suffer NETosis in comparison with anti-dsDNA(−) patients. Anti-dsDNA(+) patients further displayed altered levels of numerous circulating mediators related to inflammation, NETosis, and cardiovascular risk. In vitro, Ig-dsDNA promoted NETosis on neutrophils, apoptosis on monocytes, modulated the expression of inflammation and thrombosis-related molecules, and induced endothelial activation, at least partially, by FcR (Fc receptor)-binding mechanisms. Conclusions: Anti-dsDNA antibodies increase the cardiovascular risk of SLE patients by altering key molecular processes that drive a distinctive and coordinated immune and vascular activation, representing a potential tool in the management of this comorbidity.

Characterization of Antiphospholipid Syndrome Atherothrombotic Risk by Unsupervised Integrated Transcriptomic Analyses.

OBJECTIVE: Our aim was to characterize distinctive clinical antiphospholipid syndrome phenotypes and identify novel microRNA (miRNA)-mRNA-intracellular signaling regulatory networks in monocytes linked to cardiovascular disease. Approach and Results: Microarray analysis in antiphospholipid syndrome monocytes revealed 547 differentially expressed genes, mainly involved in inflammatory, cardiovascular, and reproductive disorders. Besides, this approach identified several genes related to inflammatory, renal, and dermatologic diseases. Functional analyses further demonstrated phosphorylation of intracellular kinases related to thrombosis and immune-mediated chronic inflammation. miRNA profiling showed altered expression of 22 miRNAs, enriched in pathways related to immune functions, cardiovascular disease, and autoimmune-associated pathologies. Unbiased integrated mRNA-miRNA analysis identified a signature of 9 miRNAs as potential modulators of 17 interconnected genes related to cardiovascular disease. The altered expression of that miRNA-mRNA signature was proven to be stable along time and distinctive of nonautoimmune thrombotic patients. Transfection studies and luciferase assays established the relationship between specific miRNAs and their identified target genes and proteins, along with their involvement in the regulation of monocytes procoagulant activity and cell adhesion. Correlation analyses showed relationship among altered miRNAs and their interconnected genes with aPL (antiphospholipid antibodies)-titers, along with microvascular endothelial dysfunction. In vitro studies demonstrated modulation in healthy monocytes by IgG-aPLs of several genes/miRNAs, which further intermediated downstream effects on endothelial function. The identified transcriptomic signature allowed the unsupervised division of three clusters of patients with antiphospholipid syndrome showing distinctive clinical profiles, mainly associated with their prothrombotic risk (thrombosis, autoantibody profile, cardiovascular risk factors, and atherosclerosis). CONCLUSIONS: Extensive molecular profiling of monocytes in patients with primary antiphospholipid syndrome might help to identify distinctive clinical phenotypes, thus enabling new patients' tailored treatments.

Variation in training requirements within general surgery: comparison of 23 countries.

Background: Many differences exist in postgraduate surgical training programmes worldwide. The aim of this study was to provide an overview of the training requirements in general surgery across 23 different countries. Methods: A collaborator affiliated with each country collected data from the country's official training body website, where possible. The information collected included: management, teaching, academic and operative competencies, mandatory courses, years of postgraduate training (inclusive of intern years), working-hours regulations, selection process into training and formal examination. Results: Countries included were Australia, Belgium, Canada, Colombia, Denmark, Germany, Greece, Guatemala, India, Ireland, Italy, Kuwait, the Netherlands, New Zealand, Russia, Saudi Arabia, South Africa, South Korea, Sweden, Switzerland, UK, USA and Zambia. Frameworks for defining the outcomes of surgical training have been defined nationally in some countries, with some similarities to those in the UK and Ireland. However, some training programmes remain heterogeneous with regional variation, including those in many European countries. Some countries outline minimum operative case requirement (range 60-1600), mandatory courses, or operative, academic or management competencies. The length of postgraduate training ranges from 4 to 10 years. The maximum hours worked per week ranges from 38 to 88 h, but with no limit in some countries. Conclusion: Countries have specific and often differing requirements of their medical profession. Equivalence in training is granted on political agreements, not healthcare need or competencies acquired during training.

Antecedentes: Existen muchas diferencias entre los programas de formación quirúrgica de posgrado del mundo. El objetivo de este estudio fue proporcionar una visión general de los requisitos formativos en cirugía general en 23 países diferentes. Métodos: En cada uno de los países participantes, un colaborador recopiló datos de la página web del organismo oficial encargado de la formación, si era posible. La información incluyó: gestión, formación, competencias académicas y operatorias, cursos obligatorios, años de formación de postgrado (que incluía el período de internado), regulaciones sobre las horas de trabajo, proceso de selección para la formación y existencia de un examen final. Resultados: Se incluyeron los datos de Australia, Bélgica, Canadá, Colombia, Dinamarca, Alemania, Grecia, Guatemala, India, Irlanda, Italia, Kuwait, Países Bajos, Nueva Zelanda, Rusia, Arabia Saudita, Sudáfrica, Corea del Sur, Suecia, Suiza, Reino Unido, Estados Unidos de América y Zambia. En algunos países existen los marcos normativos para definir los resultados del programa de formación, con ciertas semejanzas a los del Reino Unido e Irlanda. Sin embargo, algunos programas de formación, incluso en muchos países europeos, son muy heterogéneos con variaciones regionales. Pocos países describen el número mínimo de procedimientos quirúrgicos (rango 60 a 1.600), los cursos obligatorios o competencias quirúrgicas, académicos o de gestión exigidos. La duración de la formación postgraduada osciló de los 4 a los 10 años. El número de horas trabajadas máximas por semana oscilaron entre 38 y 88, sin límite en algunos países. Conclusión: Cada país tiene unos requisitos específicos, a menudo diferentes, para la formación de sus médicos. La convalidación se otorga por acuerdos políticos, más que por las necesidades médicas o por las competencias adquiridas durante la formación.

Salutogenic health promotion program for migrant women at risk of social exclusion.

BACKGROUND: Migrant women at risk of social exclusion often experience health inequities based on gender, country of origin or socioeconomic status. Traditional health promotion programs designed for this population have focused on covering their basic needs or modifying lifestyle behaviors. The salutogenic model of health could offer a new perspective enabling health promotion programs to reduce the impact of health inequities. This study evaluated the effectiveness of a salutogenic health promotion program focused on the empowerment of migrant women at risk of social exclusion. METHODS: A four-session salutogenic health promotion program was conducted over a period of 6 months. In a quasi-experimental pre-test post-test design, an ad hoc questionnaire was administered to 26 women to collect sociodemographic data, together with 5 validated instruments: Antonovsky's Sense of Coherence (SOC-13), Duke-UNC-11 (perceived social support), Quality of Life Short Form-36 (SF-36), Rosenberg's Self-Esteem Scale, and the Cohen et al. Perceived Stress Scale (PSS-10). Descriptive analysis and multiple linear regression models were performed. Statistical tests were considered significant with a two-tailed p value < 0.05. RESULTS: Participants had a low initial SOC-13 score (60.36; SD 8.16), which did not show significant change after the health promotion program. Perceived social support (37.07; SD 6.28) and mental quality of life also remained unchanged, while physical quality of life increased from 50.84 (SD 4.60) to 53.08 (SD 5.31) (p = 0.049). Self-esteem showed an increasing trend from 30.14 (SD 4.21) to 31.92 (SD 4.38) (p = 0.120). Perceived stress decreased from 20.57 (SD 2.91) to 18.38 (SD 3.78) (p = 0.016). A greater effect was observed at the end of the program in women with lower initial scores for SOC-13 and quality of life and higher initial scores of perceived stress. CONCLUSIONS: The health promotion program reduced perceived stress, increased physical quality of life and showed a trend toward increased self-esteem, especially among migrant women with multiple vulnerability factors. The salutogenic model of health should be considered as a good practice to apply in health promotion programs and to be included in national policies to reduce health inequity in migrant populations.