10 research outputs found
Long-term survivors in phase I clinical trials: Who are they and what predicts their survival?
Plasma sequencing of ctDNA in early stage breast cancer as part of the screening process.
Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis.
Circulating tumor DNA (ctDNA) has emerged as a non-invasive "liquid biopsy" for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy circulating DNA. Matched plasma and frozen fresh tissue biopsies from patients with Breast Imaging-Reporting and Data System (BIRADS) 4c/5 mammography findings and subsequent diagnosis of primary breast cancer were analyzed using NGS TruSeq Custom Amplicon Low Input Panel (Illumina) and plasma SafeSEQ (Sysmex Inostics). The same plasma and tumor mutations were observed in eight of 29 patients (27.6%) with four in TP53 and five in PIK3CA mutations. Sequencing analysis also revealed four additional ctDNA mutations (three in TP53 and one in PIK3CA) previously not identified in three patients tissue biopsy. One of these patients had mutations in both genes. Age, tumor grade and size, immunohistochemical (IHC) subtype, BIRADS category, and lymph node positivity were significantly associated with the detectability of these blood tumor-derived mutations. In conclusion, ctDNA analysis could be used in early breast cancer diagnosis, providing critical clinical information to improve patient diagnosis
Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
Circulating tumor DNA (ctDNA) has emerged as a non-invasive “liquid biopsy” for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy circulating DNA. Matched plasma and frozen fresh tissue biopsies from patients with Breast Imaging-Reporting and Data System (BIRADS) 4c/5 mammography findings and subsequent diagnosis of primary breast cancer were analyzed using NGS TruSeq Custom Amplicon Low Input Panel (Illumina) and plasma SafeSEQ (Sysmex Inostics). The same plasma and tumor mutations were observed in eight of 29 patients (27.6%) with four in TP53 and five in PIK3CA mutations. Sequencing analysis also revealed four additional ctDNA mutations (three in TP53 and one in PIK3CA) previously not identified in three patients tissue biopsy. One of these patients had mutations in both genes. Age, tumor grade and size, immunohistochemical (IHC) subtype, BIRADS category, and lymph node positivity were significantly associated with the detectability of these blood tumor-derived mutations. In conclusion, ctDNA analysis could be used in early breast cancer diagnosis, providing critical clinical information to improve patient diagnosis
Blinded independent validation of the PAM50-based Chemo-Endocrine Sensitivity Predictor (CESP) in hormone receptor (HR)-positive/HER2-negative (HR+/HER2-) breast cancer following neoadjuvant chemotherapy (NAC).
Different pCR rates according PAM50 defined subtypes in HER2 positive early breast cancer treated with neoadjuvant pertuzumab and trastuzumab.
Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes
Objective To compare the clinical characteristics and outcomes of
patients with acute heart failure (AHF) according to clinical profiles
based on congestion and perfusion determined in the emergency department
(ED).
Methods and results Overall, 11 261 unselected AHF patients from 41
Spanish EDs were classified according to perfusion (normoperfusion =
warm; hypoperfusion = cold) and congestion (not = dry; yes = wet).
Baseline and decompensation characteristics were recorded as were the
main wards to which patients were admitted. The primary outcome was
1-year all-cause mortality; secondary outcomes were need for
hospitalisation during the index AHF event, in-hospital all-cause
mortality, prolonged hospitalisation, 7-day post-discharge ED revisit
for AHF and 30-day post-discharge rehospitalisation for AHF. A total of
8558 patients (76.0%) were warm+ wet, 1929 (17.1%) cold+ wet, 675
(6.0%) warm+ dry, and 99 (0.9%) cold+ dry; hypoperfused (cold)
patients were more frequently admitted to intensive care units and
geriatrics departments, and warm+ wet patients were discharged home
without admission. The four phenotypes differed in most of the baseline
and decompensation characteristics. The 1-year mortality was 30.8%, and
compared to warm+ dry, the adjusted hazard ratios were significantly
increased for cold+ wet (1.660; 95% confidence interval 1.400-1.968)
and cold+ dry (1.672; 95% confidence interval 1.189-2.351).
Hypoperfused (cold) phenotypes also showed higher rates of index episode
hospitalisation and in-hospital mortality, while congestive (wet)
phenotypes had a higher risk of prolonged hospitalisation but decreased
risk of rehospitalisation. No differences were observed among phenotypes
in ED revisit risk.
Conclusions Bedside clinical evaluation of congestion and perfusion of
AHF patients upon ED arrival and classification according to phenotypic
profiles proposed by the latest European Society of Cardiology
guidelines provide useful complementary information and help to rapidly
predict patient outcomes shortly after ED patient arrival
Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk
Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Setting Prospective, international, multicentre, observational cohort study. Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. Trial registration number NCT0432364