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Background/Objectives: Early identification of patients at risk of developing severe acute pancreatitis (SAP) is still an issue. Dynamic assessment of clinical and laboratory parameters within the first 48 h of admission may offer valuable insights into the prediction of unfavorable outcomes such as SAP and death. Methods: A prospective observational study was conducted on a cohort of patients admitted for AP at a tertiary referral hospital. Clinical and laboratory data were collected on admission and at 48 h. Patients were classified based on the Revised Atlanta classification. Logistic regression analysis was performed to identify independent risk factors for SAP. Likelihood ratios and post-test probabilities were calculated to assess the clinical usefulness of predictive markers. Results: 227 patients were included, with biliary etiology being the most common and a prevalence of SAP and death of 10.7% and 5.7%, respectively. BISAP ≥ 2 on admission, presence of SIRS after 48 h, rise in heart rate over 20 bpm, and any increase in BUN after 48 h were independent risk factors for SAP. The combination of these factors increased the post-test probability of SAP and death, with BISAP ≥ 2 combined with the presence of SIRS after 48 h showing the highest probability (82% and 73%, respectively). Conclusions: Dynamic assessment of BUN, heart rate, and SIRS within the first 48 h of admission can aid in predicting the development of SAP and death in patients with AP. These findings underscore the importance of continuous monitoring, although multicenter studies are warranted to refine predictive models for SAP.
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BACKGROUND: Copy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs). METHODS: Single-nucleotide polymorphism (SNP)-array was performed on 926 biopsies from mBC patients, enrolled in SAFIR02-BREAST prospective trial. CNA profiles of eBCs from The Cancer Genome Atlas Breast Invasive Carcinoma (n = 770), Molecular Taxonomy of Breast Cancer International Consortium (n = 1620) and PACS04 trial (n = 243) cohorts were used as references for comparing mBCs and eBCs CNA profiles. Overall survival was the considered survival endpoint. RESULTS: Among the twenty-one genes frequently altered in ER + /HER2- mBCs: focal amplification of TERT was associated with poor outcome in the ER + /HER2- mBC population. Among the ER + /HER2- mBCs patients for whom CDK4/6 inhibitors information before biopsies collection was available: we identified seven genes on post-treatment biopsies, including the cyclin-dependent kinase 4 (CDK4), which was amplified in 9.8% of the ER + /HER2- mBCs pretreated population, as compared to 1.5% in the ER + /HER2- mBCs unpretreated population (P = 2.82E-04) as well as the 3 eBC populations. CDK4 amplification was associated with poor outcome in the ER + /HER2- eBCs. CONCLUSIONS: This study provides insights into the biology of mBCs and identifies clinically useful genomic features for future improvement of breast cancer patient management.
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BACKGROUND: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection. Antisense oligonucleotides (ASOs) can be rationally designed on the basis of sequence data, require no delivery system, and can be administered locally. OBJECTIVE: We sought to design ASOs that can block SARS-CoV-2 by downregulating ACE2 in human airway. METHODS: ACE2-targeting ASOs were designed using a bioinformatic method and screened in cell lines. Human primary nasal epithelial cells cultured at the air-liquid interface and humanized ACE2 mice were used to detect the ACE2 reduction levels and the safety of ASOs. ASO-pretreated nasal epithelial cells and mice were infected and then used to detect the viral infection levels. RESULTS: ASOs reduced ACE2 expression on mRNA and protein level in cell lines and in human nasal epithelial cells. Furthermore, they efficiently suppressed virus replication of 3 different SARS-CoV-2 variants in human nasal epithelial cells. In vivo, ASOs also downregulated human ACE2 in humanized ACE2 mice and thereby reduced viral load, histopathologic changes in lungs, and increased survival of mice. CONCLUSIONS: ACE2-targeting ASOs can effectively block SARS-CoV-2 infection. Our study provides a new approach for blocking SARS-CoV-2 and other ACE2-targeting virus in high-risk populations.
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INTRODUCTION: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. PATIENTS AND METHODS: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. RESULTS: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). DISCUSSION AND CONCLUSION: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.
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OBJECTIVE: The risk factors for seizure recurrence after acute symptomatic seizure due to a structural brain lesion are not well established. The aim of this study was to analyze possible associations between demographic, clinical, and electroencephalographic variables and epilepsy development in patients with acute symptomatic seizure due to an acute structural brain lesion. METHODS: We designed an observational prospective study of patients with acute symptomatic seizure due to an acute structural brain lesion (hemorrhagic stroke, ischemic stroke, traumatic brain injury, or meningoencephalitis) who underwent EEG during their initial admission between January 2015 and January 2020. We analyzed prospectively recorded demographic, clinical, electroencephalographic (EEG), and treatment-related variables. All variables were compared between patients with and without seizure recurrence during 2 years of follow up. RESULTS: We included 194 patients (41.2 % women; mean [SD] age, 57.3 [15.8] years) with acute symptomatic seizure due to an acute structural brain lesion. They all underwent EEG during admission and were followed for at least 2 years. The identifiable causes were hemorrhagic stroke (44.8 %), ischemic stroke (19.5 %), traumatic brain injury (18.5 %), and meningoencephalitis (17 %). Fifty-six patients (29 %) experienced a second seizure during follow-up. Seizure recurrence was associated with epileptiform discharges on EEG (52% vs 32 %; OR 2.3 [95 % CI, 1.2-4.3], p = 0.008) and onset with status epilepticus (17% vs 0.05 %, OR 4.03 [95 % CI 1.45-11.2], p = 0.009). CONCLUSIONS: Epileptiform discharges on EEG and status epilepticus in patients with acute symptomatic seizure due to an acute structural brain lesion are associated with a higher risk of epilepsy development.
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Electroencefalografía , Recurrencia , Convulsiones , Humanos , Femenino , Masculino , Persona de Mediana Edad , Convulsiones/fisiopatología , Convulsiones/etiología , Adulto , Anciano , Estudios Prospectivos , Factores de Riesgo , Meningoencefalitis/fisiopatología , Meningoencefalitis/complicaciones , Estudios de SeguimientoRESUMEN
BACKGROUND: To identify patients most likely to respond to everolimus, a mammalian target of rapamycin (mTOR) inhibitor, a prospective biomarker study was conducted in hormone receptor-positive endocrine-resistant metastatic breast cancer patients treated with exemestane-everolimus therapy. METHODS: Metastatic tumor biopsies were processed for immunohistochemical staining (p4EBP1, PTEN, pAKT, LKB1, and pS6K). ESR1, PIK3CA and AKT1 gene mutations were detected by NGS. The primary endpoint was the association between the p4EBP1 expression and clinical benefit rate (CBR) at 6 months of everolimus plus exemestane treatment. RESULTS: Of 150 patients included, 107 were evaluable for the primary endpoint. p4EBP1 staining above the median (Allred score ≥6) was associated with a higher CBR at 6 months (62% versus 40% in high-p4EBP1 versus low-p4EBP1, χ2 test, p = 0.026) and a longer progression-free survival (PFS) (median PFS of 9.2 versus 5.8 months in high-p4EBP1 versus low-p4EBP1; p = 0.02). When tested with other biomarkers, only p4EBP1 remained a significant predictive marker of PFS in multivariate analysis (hazard ratio, 0.591; p = 0.01). CONCLUSIONS: This study identified a subset of patients with hormone receptor-positive endocrine-resistant metastatic breast cancer and poor outcome who would derive less benefit from everolimus and exemestane. p4EBP1 may be a useful predictive biomarker in routine clinical practice. CLINICAL TRIAL REGISTRATION: NCT02444390.
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Neoplasias de la Mama , Everolimus , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Androstadienos/uso terapéutico , Biomarcadores , Receptor ErbB-2/metabolismoRESUMEN
(1) Background: Colorectal cancer (CRC) is one of the most common causes of cancer. Timely diagnosis is critical, with even minor delays impacting prognosis. Primary care providers face obstacles in accessing specialist care. This study investigates the impact of implementing an electronic consultation (eConsult) system combined with a specific prioritization system on CRC diagnosis delay and tumor staging. (2) Methods: The study analyzes 245 CRC patients from November 2019 to February 2022, comparing those referred before and after the eConsult system's implementation during the COVID-19 pandemic. Data on referral reasons, pathways, diagnosis delays, and staging were collected. Multivariate analysis aimed to identify independent risk factors for advanced staging at diagnosis. (3) Results: The eConsult system significantly reduced CRC diagnosis delay from 68 to 26 days. The majority of patients referred via eConsult presented with symptoms. Despite expedited diagnoses, no discernible difference in CRC staging emerged between eConsult and traditional referrals. Notably, patients from screening programs or with a positive fecal immunochemical test (FIT) experienced earlier-stage diagnoses. A positive FIT without symptoms and being a never-smoker emerged as protective factors against advanced-stage CRC. (4) Conclusions: This study highlights eConsult's role in reducing CRC diagnosis delay, improving diagnostic efficiency and prioritizing urgent cases, emphasizing FIT effectiveness.
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INTRODUCTION AND OBJECTIVES: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is considered more reliable, efficient, and safer than conventional in-person follow-up. However, the implementation of RM is still suboptimal. This study aimed to analyze the impact of the COVID-19 pandemic on the rates of CIED implants and RM activations in Spain. METHODS: The COVID-19 RM Spain Registry was used to analyze the monthly number of all CIED implantations and RM activations from January 2018 to December 2021. A descriptive analysis was performed using aggregated data from the five major CIED manufacturers. RESULTS: A total of 205 345 CIEDs were recorded. The number of implants decreased sharply (48.2%) during the pandemic lockdown (March-June 2020) but gradually increased thereafter, compensating for the previous reduction. However, pacemakers and implantable cardiac defibrillators (ICD) showed an aggregate loss of 7% and 3%, respectively, from the annual average during 2020-2021. In contrast, cardiac resynchronization therapy defibrillators (CRT-D) increased by 17%, and pacemakers (CRT-P) by 4.5% over the 2-year period. The percentage of RM activations increased from 24.5% in 2018 to 49.0% in 2021, with a sharp increase during the lockdown. The RM activation rates consistently increased during the lockdown for all devices: pacemakers (14.4% vs 37.2%; P <.001); ICD (75.6% vs 94.2%; P <.001); CRT-D/CRT-P (68.6-44.2% vs 81.6-61%; P <.001), and implantable loop recorders (50.2% vs 68.7%; P <.001). CONCLUSIONS: The significant decline in implants during the lockdown gradually recovered, except for pacemakers and ICD. However, the COVID-19 pandemic boosted RM for all CIEDs in Spain.
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COVID-19 , Terapia de Resincronización Cardíaca , Desfibriladores Implantables , Marcapaso Artificial , Humanos , Pandemias , COVID-19/epidemiología , Control de Enfermedades TransmisiblesRESUMEN
BACKGROUND: The p53 mutation in breast cancer confers a worse prognosis and is usually associated with p53 overexpression (p53+) on immunohistochemistry. Previous studies have shown that p53+ tumors could be associated with low axillary tumor burden (ATB). OBJECTIVE: We aimed to evaluate the association between p53+ and ATB in a large series of breast cancers as an aid to personalizing axillary surgical treatment. METHODS: We retrieved 1762 infiltrating breast carcinomas from our database that were treated with upfront surgery in Hospital del Mar from 2004 to 2018. We compared p53+ and p53-negative (p53-) tumors in terms of the percentage of cases with high ATB and overall survival. This comparison was made overall and for each immunophenotype. RESULTS: Overall, 18.7% of breast tumors were p53+. High ATB was less common in p53+ tumors than in p53- tumors in the luminal B-Her2-negative immunophenotype (6.2% versus 16.9%, respectively, P = 0.025), but not in the other immunophenotypes or overall. Overall survival was worse in patients with p53+ breast cancer (P = 0.002). CONCLUSION: p53+ breast cancers were associated with worse overall survival. However, low ATB was more common in these tumors than in p53- tumors in the luminal B-Her2-negative subtype. Information on p53 expression could be of use to predict ATB in some breast cancer tumors.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Proteína p53 Supresora de Tumor/genética , Carga Tumoral , Pronóstico , Inmunohistoquímica , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismoRESUMEN
There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.
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Neoplasias de Cabeza y Cuello , Quinazolinas , Humanos , Afatinib/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Biomarcadores , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
SARS-CoV-2 infection is the cause of the disease named COVID-19, a major public health challenge worldwide. Differences in the severity, complications and outcomes of the COVID-19 are intriguing and, patients with similar baseline clinical conditions may have very different evolution. Myeloid-derived suppressor cells (MDSCs) have been previously found to be recruited by the SARS-CoV-2 infection and may be a marker of clinical evolution in these patients. We have studied 90 consecutive patients admitted in the hospital before the vaccination program started in the general population, to measure MDSCs and lymphocyte subpopulations at admission and one week after to assess the possible association with unfavorable outcomes (dead or Intensive Care Unit admission). We analyzed MDSCs and lymphocyte subpopulations by flow cytometry. In the 72 patients discharged from the hospital, there were significant decreases in the monocytic and total MDSC populations measured in peripheral blood after one week but, most importantly, the number of MDSCs (total and both monocytic and granulocytic subsets) were much higher in the 18 patients with unfavorable outcome. In conclusion, the number of circulating MDSCs may be a good marker of evolution in the follow-up of unvaccinated patients admitted in the hospital with the diagnosis of COVID-19.
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COVID-19 , Células Supresoras de Origen Mieloide , Humanos , Estudios de Seguimiento , SARS-CoV-2 , Biomarcadores , HospitalizaciónRESUMEN
INTRODUCTION AND OBJECTIVES: This article reports the cardiac pacing activity performed in 2022, including the total number of implants, adherence to remote monitoring, demographic and clinical factors, and the characteristics of the implanted devices. METHODS: The information sources were the CardioDispositivos online platform, the European pacemaker patient identification card, and data provided by the manufacturers. RESULTS: The rates of conventional pacemakers and low-energy resynchronizers were 866 and 34 units per million population, respectively. A total of 815 leadless pacemakers were implanted. In all, 16426 procedures performed in 82 hospitals were reported (9407 through CardioDispositivos), representing 40% of the activity. The mean age was 78.6 years, with a predominance of men (60.3%). The most frequent disorder was atrioventricular block, and 14.5% of the patients had atrial fibrillation. There was a predominance of the DDD/R pacing mode (55.6%), and pacing mode was influenced by age, such that more than one-third of patients older than 80 years in sinus rhythm received single-chamber ventricular pacing. The remote monitoring program included 35% of conventional pacemakers and 55% of low-energy resynchronization pacemakers. CONCLUSIONS: The number of conventional pacemakers increased by 5.6%, low-energy resynchronizers by 16%, and leadless pacemakers by 25%. Adherence to remote monitoring was stable. The number of procedures included in CardioDispositivos increased by 11%, although the sample volume decreased. In the coming years, the widespread use of the platform will likely lead to a high-quality registry.
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Fibrilación Atrial , Cardiología , Marcapaso Artificial , Masculino , Humanos , Anciano , Anciano de 80 o más Años , Femenino , Estimulación Cardíaca Artificial , Sociedades Médicas , Sistema de RegistrosRESUMEN
Snijders Blok-Campeau syndrome (SNIBCPS, OMIM# 618205) is an extremely infrequent disease with only approximately 60 cases reported so far. SNIBCPS belongs to the group of neurodevelopmental disorders (NDDs). Clinical features of patients with SNIBCPS include global developmental delay, intellectual disability, speech and language difficulties and behavioral disorders like autism spectrum disorder. In addition, patients with SNIBCPS exhibit typical dysmorphic features including macrocephaly, hypertelorism, sparse eyebrows, broad forehead, prominent nose and pointed chin. The severity of the neurological effects as well as the presence of other features is variable among subjects. SNIBCPS is caused likely by pathogenic and pathogenic variants in CHD3 (Chromodomain Helicase DNA Binding Protein 3), which seems to be involved in chromatin remodeling by deacetylating histones. Here, we report 20 additional patients with clinical features compatible with SNIBCPS from 17 unrelated families with confirmed likely pathogenic/pathogenic variants in CHD3. Patients were analyzed by whole exome sequencing and segregation studies were performed by Sanger sequencing. Patients in this study showed different pathogenic variants affecting several functional domains of the protein. Additionally, none of the variants described here were reported in control population databases, and most computational predictors suggest that they are deleterious. The most common clinical features of the whole cohort of patients are global developmental delay (98%) and speech disorder/delay (92%). Other frequent features (51-74%) include intellectual disability, hypotonia, hypertelorism, abnormality of vision, macrocephaly and prominent forehead, among others. This study expands the number of individuals with confirmed SNIBCPS due to pathogenic or likely pathogenic variants in CHD3. Furthermore, we add evidence of the importance of the application of massive parallel sequencing for NDD patients for whom the clinical diagnosis might be challenging and where deep phenotyping is extremely useful to accurately manage and follow up the patients.
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Discapacidades del Desarrollo , Hipertelorismo , Discapacidad Intelectual , Trastornos del Desarrollo del Lenguaje , Megalencefalia , Humanos , ADN Helicasas/genética , Histonas , Discapacidad Intelectual/genética , Megalencefalia/genética , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , Discapacidades del Desarrollo/genéticaRESUMEN
BACKGROUND: Vaccination of pigs against PCV2 is usually performed around weaning when animals still have maternally derived antibodies (MDA). The present study aimed to assess the possible interference of MDA in the development of the PCV2-specific immune response after vaccination of commercial weaners. For this purpose, a PRRS-negative 600-sow farrow-to-finish farm was selected. Half of the sows were vaccinated and revaccinated with Porcilis® PCV ID against PCV2 7 and 3 weeks before farrowing. After farrowing, piglets were tested by AlphaLisa to select 72 animals with high and low levels of MDA. Groups were further subdivided and vaccinated intradermally with Porcilis® PCV ID at 21 or 28 days of age. Unvaccinated controls were also included. Animals were followed afterward for 42 days to examine the development of PCV2-specific antibodies and interferon-γ secreting cells (IFN-γ SC). RESULTS: The average titres of antibodies of the groups vaccinated in the presence of low or high MDA levels were similar at 28 and 42 days post-vaccination while in the controls the titres declined throughout the observation period. Results of vaccinating at 21 or 28 days of age were equivalent with regard to antibody development. Regarding the IFN-γ SC, vaccinated animals produced significant frequencies of IFN-γ SC by day 28. Again, no differences were observed between the groups with high or low antibody levels. CONCLUSION: High levels of MDA did not interfere with the development of humoral and cell-mediated responses to Porcine circovirus 2 after intradermal vaccination at 21 or 28 days of age.
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The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2-drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3-81) in cohort 1, 37.5% (95% CI 26.4-49.7) in cohort 2 and 29.7% (95% CI 15.9-47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8-64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7-65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960 .).
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Neoplasias de la Mama , Inmunoconjugados , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Trastuzumab/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Camptotecina/uso terapéuticoRESUMEN
BACKGROUND: Patient-reported outcome measures (PROMs) have gained considerable interest in health care moving beyond traditional outcome measures of morbidity and mortality. In breast cancer surgery, women's' perceptions of appearance, function and quality of life have become increasingly important. The BREAST-Q questionnaire is a validated PROM for use in cosmetic and reconstructive breast surgery in clinical practice. The objective of this study was to validate the Spanish electronic version of the BREAST-Q questionnaire, to verify the measurement equivalence of digital and paper versions and to identify the possible disadvantages and advantages of implementing this new tool. METHODS: The study population included 113 patients undergoing breast cancer survey at a single hospital in Barcelona (Spain) who were able to complete both the electronic and paper versions of the preoperative module of the BREAST-Q questionnaire. RESULTS: The intraclass correlation coefficient (ICC) in the four domains of the questionnaire between the two versions of the questionnaire was >0.9, with a weighted kappa of >0.74 at item level. The reliability of the internal consistency was also excellent, with Cronbach's alpha coefficient of >0.70 in all domains. Age was a limiting factor for the delivery of the electronic version of BREAST-Q, with 69 years of age as the cut-off point to obtain reliable results. CONCLUSIONS: The interchangeability of the electronic and paper versions of the BREAST-Q questionnaire facilitates implementation of this instrument in routine surgical oncological practice.
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Neoplasias de la Mama , Calidad de Vida , Humanos , Femenino , Anciano , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Mama , Neoplasias de la Mama/cirugíaRESUMEN
Antisense oligonucleotides (ASOs) are a novel therapeutic strategy that targets a specific gene and suppresses its expression. The cryopyrin-associated periodic syndromes (CAPS) are a spectrum of autoinflammatory diseases characterized by systemic and tissue inflammation that is caused by heterozygous gain-of-function mutations in the nucleotide-binding and oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) gene. The aim of this study was to investigate the efficacy of an Nlrp3-specific ASO treatment in CAPS. An Nlrp3-specific ASO was designed and tested in murine cell lines and bone marrow-derived macrophages (BMDMs) from wild-type and CAPS mouse models. Nlrp3 knock-in mice were treated in vivo with Nlrp3-specific ASO, survival was monitored, and expression of organ-specific Nlrp3 and IL-1ß was measured. Nlrp3-specific ASO treatment of murine cell lines and BMDMs showed a significant downregulation of Nlrp3 and mature IL-1ß protein expression. Ex vivo treatment of Nlrp3 mutant mouse-derived BMDMs with Nlrp3-specific ASO demonstrated significantly reduced IL-1ß release. In vivo, Nlrp3-specific ASO treatment of Nlrp3 mutant mice prolonged survival, reduced systemic inflammation, and decreased tissue-specific expression of Nlrp3 and mature IL-1ß protein. The results of this study demonstrate that Nlrp3-specific ASO treatment downregulates Nlrp3 expression and IL-1ß release in CAPS models, suggesting ASO therapy as a potential treatment of CAPS and other NLRP3-mediated diseases.
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Síndromes Periódicos Asociados a Criopirina , Proteína con Dominio Pirina 3 de la Familia NLR , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Síndromes Periódicos Asociados a Criopirina/genética , Inflamación , Proteínas Portadoras/genética , Interleucina-1beta/metabolismoRESUMEN
Background: Nowadays the poly-ADP ribose polymerase inhibitors (iPARPs) are the mainly treatment for the ovarian cancer and other solid tumours. However, given its recent use, long-term toxicity is still under study. The occurrence of acute leukaemias and myelodysplastic syndromes (MDS) secondarily to iPARPs is known (0.5-1%). Case Description: We present the case of a 78-year-old patient with a serous carcinoma of ovary in maintenance treatment with Niraparib after response to platinum. Along with the ovarian carcinoma the patient developed a diffuse large cell B lymphoma (DLBCL) five years ago, treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) with complete response. The patient was evaluated in the emergency due to constitutional syndrome, objectifying a bicytopenia (platelets 28,000/mcL, haemoglobin 9.6 g/dL). In the study of bicytopenia, a bone marrow infiltration by high-grade B lymphoma was diagnosed. Conclusions: The action of iPARPs on the selection of acquired mutations in clonal haematopoiesis maybe have been able to accelerate the process of relapse and leukemisation of the previous lymphoma. The association of treatment with iPARPs and the development of lymphomas is key for increasing knowledge of the safety profiles these drugs.
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Background: Some studies suggested that the patients included in the Z0011 trial may represent patients with ultrasound-negative axillary nodes and axillary invasion diagnosed by sentinel node (SN) biopsy. Nevertheless, the National Comprehensive Cancer Network (NCCN) guidelines recommend SN mapping if 1 or 2 suspicious lymph nodes are identified on axillary ultrasound (AU). The aim of this preliminary phase of the Multimodal Targeted Axillary Surgery (MUTAS) trial was to establish the accuracy of SN mapping in patients with axillary involvement undergoing upfront surgery. Methods: Between September 2019 and March 2022, we recruited patients with biopsy-proven metastatic axillary nodes and upfront surgery from a single center. We performed SN mapping in these patients before the surgical intervention, which included axillary lymph node dissection. The biopsy-proven metastatic node, SNs and the remaining axillary nodes were excised separately. SN status was considered representative of the status of the remaining axillary nodes. We calculated the sensitivity, specificity, negative predictive value and positive predictive value of the SN, overall and in patients with palpable nodes, in those with non-palpable nodes and an AU leading to diagnosis of axillary involvement, in those with 1 or 2 suspicious nodes on AU, and in patients with a single suspicious node on AU. We evaluated clinical, imaging and pathology features as predictors of the status of the remaining axillary nodes, false-negatives, and false-positives. Results: We included 25 patients in this phase. The false-negative rate of SN mapping was 28% overall, 21.42% for patients with palpable nodes, 36.36% for patients with non-palpable nodes and an AU diagnosis of axillary involvement, 28.75% for those with 1 or 2 suspicious nodes on AU, and 15.38% in patients with a single suspicious node on AU. The negative predictive value was highest in patients with a single suspicious node on AU (75%). The only significant predictive factor was that FN showed a higher Ki67 index score. Conclusions: In this study, SN mapping was not reliable in patients with biopsy-proven metastatic axillary nodes and upfront surgery for any of the subgroups studied. Further research should elucidate the best staging pathways in these patients to avoid premature de-escalation.