Publications by authors named "Carlos Barrios"

197 Publications

Inability of Laplace's law to estimate sub-bandage pressures after applying a compressive bandage: a clinical study.

J Wound Care 2021 Apr;30(4):276-282

Institute for Research on Musculoskeletal Disorders, Valencia Catholic University Saint Vincent Martyr, Valencia, Spain.

Objective: The aim of the current study was to compare pressures exerted on the lower limb by a high compression bandage as recorded by sub-bandage sensors and those estimated by Laplace's law. The correlation between pressures obtained in each anatomical zone and the corresponding limb perimeters were explored.

Method: For the measurement of sub-bandage pressures, four anatomical zones in the lower right limb were determined. Pressures were recorded by nine pneumatic sensors and a PicoPress transducer. A two-layer compression bandage system (UrgoK2, Urgo Group, France) was used for the dressing. Pressures were registered in supine position. Sensor pressures were compared with those estimated by a modified Laplace's equation.

Results: A total of 47 female volunteers were recruited (mean age: 21.9±2.3 years) to the study. In the four anatomical segments studied, pressures obtained by the sensors were lower than would be expected by applying Laplace's law (p<0.05). The biggest difference between the two methods was found at the supramalleolar level (42.1% lower by sensors compared with Laplace's equation). The correlation coefficient between pressure recorded by the sensors and that calculated at the perimeters was very weak, ranging from 0.5233 to 0.9634.

Conclusion: Laplace's law, used to predict the sub-bandage pressure after applying a compressive bandage in the lower limb, was not useful, providing significantly higher pressures than those obtained by pneumatic sensors. Laplace's law underestimates the variable musculoskeletal components at the different segments of lower limb that act as compression damping forces.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12968/jowc.2021.30.4.276DOI Listing
April 2021

Is Independent Clinical Research Possible in Low- and Middle-Income Countries? A Roadmap to Address Persistent and New Barriers and Challenges.

Am Soc Clin Oncol Educ Book 2021 Mar;41:1-10

Oncoclinicas Group, São Paulo, Brazil.

Cancer is an increasing and significant problem for both high- and low- and middle-income countries. Basic, translational, and clinical research efforts have been instrumental in generating the outstanding improvements we have witnessed over the last few decades, answering important questions, and improving patient outcomes. Arguably, a substantial portion of currently ongoing research is sponsored by the pharmaceutical industy and specifically addresses questions under industry interests, most of which apply to high-income countries, leaving behind problems related to the much larger and underserved population of patients with cancer in low- and middle-income countries. In this scenario, discussing independent academic research is an important challenge, particularly for these countries. Although different countries and institutions face different problems while establishing independent research agendas, some generalizable barriers can be identified. A solid regulatory and ethical framework, a strong and sustainable technical supporting infrastructure, and motivated and experienced investigators are all paramount to build a viable and productive academic research program. Securing funding for research, although not the only hurdle, is certainly one of the most basic hurdles to overcome. Noticeably, and as an added impediment, public and governmental support for cancer research has been decreasing in high-income countries and is almost nonexistent in the rest of the world. We propose an initial careful diagnostic assessment of the research resource scenario of each institution/country and adjustment of the strategic development plan according to four different research resource restriction levels. Although not necessarily applicable to all situations, this model can be helpful if adjusted to each local or regional situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/EDBK_321335DOI Listing
March 2021

Challenge of Incorporating New Drugs for Breast Cancer in Brazil: A Proposed Framework for Improving Access to Innovative Therapies.

JCO Glob Oncol 2021 Apr;7:474-485

Hospital Moinhos de Vento, Femama, Porto Alegre, Brazil.

Purpose: The objective of this review is to address the barriers limiting access to treatment of advanced metastatic breast cancer (mBC) in Brazil, specifically for patients in the public health care system, arguably those with the least access to innovation.

Materials And Methods: A selected panel of Brazilian experts in BC were provided with a series of relevant questions to address in a multiday conference. During the conference, responses were discussed and edited by the entire group through numerous drafts and rounds of discussion until a consensus was achieved.

Results: The authors propose specific and realistic recommendations for implementing access to new drugs in cancer care in Brazil. Moreover, in creating these recommendations and framework, the authors strive to address the most important barriers and impediments for technology incorporation. A feasible and specific multidisciplinary process is proposed, which is based on the collective participation of all involved stakeholders.

Conclusion: Given the current benefits and likely future developments, there is a great need to expand treatments for mBC not only in Brazil but also in most other countries in the world where access issues remain an unresolved demand. Adapting the current framework is essential for accomplishing this goal. The recommendations in this review can serve as a framework for adoption of new technologies in countries with limited resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/GO.20.00566DOI Listing
April 2021

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

Eur J Cancer 2021 Mar 22;148:287-296. Epub 2021 Mar 22.

Institute Jules Bordet and l' Université Libre de Bruxelles (U.L.B), Brussels, Belgium.

Aim: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.

Patients And Methods: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac).

Results: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups.

Conclusion: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer.

Trial Registration: clinicaltrials.gov Identifier NCT00490139.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.01.053DOI Listing
March 2021

High Rate of Studies with Level 1 and 2 Evidence among the 100 Most Cited Articles in Lumbar Spinal Stenosis.

J Neurol Surg A Cent Eur Neurosurg 2021 Mar 9. Epub 2021 Mar 9.

Institute for Research on Musculoskeletal Disorders, School of Medicine, Valencia Catholic University of Valencia, Valencia, Spain.

Background:  To date, no study has used bibliometric analysis to review the most influential articles in lumbar spinal stenosis. The objective of this study was to identify and analyze the characteristics and the level of evidence of the 100 most cited articles on lumbar spinal stenosis METHODS:  The Thomson Reuters Web of Science was accessed to find the 100 most cited articles on lumbar spinal stenosis. For each article, we recorded the number and density of citations, authors, country, journals and years, department, level of evidence, type of study, and if it was part of any multicenter studies.

Results:  Until January 2017, the 100 most cited articles accumulated 11,136 citations (average: 259.05/y), ranging individually between 442 and 50 (average: 111.36). The first reference was published in 1974 in . Therapeutic studies ( = 40), the 1990s ( = 46), United States as country of origin ( = 51), Harvard University as institution ( = 16), Katz JN as author ( = 10), and Spine as journal ( = 48) have the hegemony. Many were multicenter ( = 42) and using level 2 evidence ( = 49). There is an inverse relationship between citation index and long-standing studies, maintenance of those most cited, and a temporary advance toward better levels of evidence.

Conclusion:  This bibliometric analysis reveals a good level of evidence in the published clinical series and includes 100 articles useful for the approach of lumbar spinal stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1720993DOI Listing
March 2021

Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451.

J Clin Oncol 2021 Apr 8;39(12):1349-1359. Epub 2021 Mar 8.

Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Purpose: In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC.

Methods: Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested.

Results: Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; = .37; median, 9.2 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%).

Conclusion: Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02212DOI Listing
April 2021

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

N Engl J Med 2021 03;384(9):829-841

From the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London (T.P.); the Bradford Hill Clinical Research Center, Santiago, Chile (M.B.); the Department of Medical Oncology, Gustave Roussy, Villejuif, France (B.E.); the Department of Hemato-Oncology, Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City (M.T.B.), the Department of Medical Oncology, Centro Universitario contra el Cáncer, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Nuevo León (V.M.O.J.), and the Department of Medical Oncology, Hospital H+ Querétaro, Querétaro (J.P.F.) - all in Mexico; the Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz (B.Z.), and the Department of Clinical Oncology and Hematology, Regional Specialist Hospital, Biała Podlaska (J. Żołnierek) - both in Poland; the Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis (J.J.H.); Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua (U.B.), the Department of Medical Oncology, Ospedale San Donato, Istituto Toscano i, Arezzo (A.H.), the Department of Internal Medicine, University of Pavia, Pavia (C.P.), and the University of Bari "A. Moro," Bari (C.P.) - all in Italy; the Department of Genitourinary Medical Oncology, M.D. Anderson Cancer Center, Houston (A.Y.S.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Medical Oncology, Royal Brisbane and Women's Hospital, Herston, QLD (J.C.G.), and Cabrini Monash University Department of Medical Oncology, Cabrini Health, Malvern, VIC (D.P.) - both in Australia; the Oncology Research Center, Hospital São Lucas, Porto Alegre, Brazil (C.B.); Fundacion Richardet Longo, Instituto Oncologico de Cordoba, Cordoba (M.R.), and Instituto Multidisciplinario de Oncología, Clínica Viedma, Viedma (R.K.) - both in Argentina; the Division of Medical Oncology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora (E.R.K.); the Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Y.T.), and the Department of Urology, Keio University School of Medicine, Tokyo (R.M.) - both in Japan; the Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); the Departments of Clinical Research (J. Zhang.), Clinical Oncology (M.A.M.), Biostatistics (B.S.), and Health Economics and Outcomes Research (F.E.), Bristol Myers Squibb, Princeton, NJ; the Department of Clinical Oncology, Exelixis, Alameda, CA (G.M.S.); the Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (A.B.A.); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).

Background: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.

Methods: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point.

Results: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib.

Conclusions: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2026982DOI Listing
March 2021

Vertebral Coplanar Alignment Technique Versus Bilateral Apical Vertebral Derotation Technique in Neuromuscular Scoliosis.

Global Spine J 2021 Feb 9:2192568221992313. Epub 2021 Feb 9.

Redsalud, Santiago, Chile.

Study Design: Single-center retrospective analysis of prospectively collected data.

Objective: Our aim was to compare the correction capacity in 3 planes of the VCA technique versus the AD technique in neuromuscular scoliosis patients.

Methods: We analized patients with neuromuscular scoliosis that underwent posterior spinal fusion from 2013 to 2017 using 2 different techniques for correction: vertebral coplanar alignment (VCA) that takes into consideration the fact that the medial cortex is more resistant than the lateral cortex, with more anchor points for better distribution of forces and ligamentotaxis and the more widely spread apical derotation (AD) technique. Clinical, surgical, and radiographic information of patients operated on with the AD technique were compared to those operated on with the VCA technique in the coronal, sagittal and axial plane at pre-op, immediate post-op, and 2 year follow-up.

Results: 64 patients met inclusion criteria, 34 patients underwent the VCA technique and 30 patients underwent the AD technique. The 2 cohorts did not differ in terms of demographics, clinical presentation or preoperative alignment. There were no significant differences in the correction ability between both techniques regarding curve magnitude, apical vertebral rotation, or pelvic obliquity. There was a significant decrease in thoracic kyphosis in the AD group compared to the VCA group in the immediate postop period (4.2 ± 26.6º for VCA and 13.2 ± 21.3º for AD (p = 0.048)).

Conclusion: Both apical derotation technique and vertebral coplanar alignment allow for correction in the 3 planes for patients with neuromuscular scoliosis. VCA is a less hypokyphosing technique than AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2192568221992313DOI Listing
February 2021

Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study.

J Natl Cancer Inst 2021 Feb 1. Epub 2021 Feb 1.

Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

Background: Understanding the impact of the tumor immune microenvironment and BRCA-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer (mTNBC). In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA alterations were evaluated for association with clinical benefit with atezolizumab (A) + nab-paclitaxel (nP) vs placebo + nP in unresectable locally advanced or mTNBC.

Methods: Patients were randomized 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) + atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival (PFS) and overall survival (OS) were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells (TC), intratumoral CD8, stromal tumor-infiltrating lymphocytes (sTILs), and BRCA1/2 mutations.

Results: PD-L1 IC+ in either primary or metastatic tumor tissue was linked to PFS and OS benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and sTILs positivity were associated with PD-L1 IC+ status; A+nP vs P+nP improved outcomes were observed only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status.

Conclusions: Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.S.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djab004DOI Listing
February 2021

Determinants of COVID-19 Mortality in Patients With Cancer From a Community Oncology Practice in Brazil.

JCO Glob Oncol 2021 01;7:46-55

Oncoclínicas Group, São Paulo, Brazil.

Purpose: The COVID-19 pandemic remains a public health emergency of global concern. Determinants of mortality in the general population are now clear, but specific data on patients with cancer remain limited, particularly in Latin America.

Materials And Methods: A longitudinal multicenter cohort study of patients with cancer and confirmed COVID-19 from Oncoclínicas community oncology practice in Brazil was conducted. The primary end point was all-cause mortality after isolation of the SARS-CoV-2 by Real-Time Polymerase Chain Reaction (RT-PCR) in patients initially diagnosed in an outpatient environment. We performed univariate and multivariable logistic regression analysis and recursive partitioning modeling to define the baseline clinical determinants of death in the overall population.

Results: From March 29 to July 4, 2020, 198 patients with COVID-19 were prospectively registered in the database, of which 167 (84%) had solid tumors and 31 (16%) had hematologic malignancies. Most patients were on active systemic therapy or radiotherapy (77%), largely for advanced or metastatic disease (64%). The overall mortality rate was 16.7% (95% CI, 11.9 to 22.7). In univariate models, factors associated with death after COVID-19 diagnosis were age ≥ 60 years, current or former smoking, coexisting comorbidities, respiratory tract cancer, and management in a noncurative setting ( < .05). In multivariable logistic regression and recursive partitioning modeling, only age, smoking history, and noncurative disease setting remained significant determinants of mortality, ranging from 1% in cancer survivors under surveillance or (neo)adjuvant therapy to 60% in elderly smokers with advanced or metastatic disease.

Conclusion: Mortality after COVID-19 in patients with cancer is influenced by prognostic factors that also affect outcomes of the general population. Fragile patients and smokers are entitled to active preventive measures to reduce the risk of SARS-CoV-2 infection and close monitoring in the case of exposure or COVID-19-related symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/GO.20.00444DOI Listing
January 2021

Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer.

NPJ Breast Cancer 2021 Jan 4;7(1). Epub 2021 Jan 4.

Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain.

Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-020-00208-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782714PMC
January 2021

Poor Bone Quality in Patients With Amyotrophic Lateral Sclerosis.

Front Neurol 2020 18;11:599216. Epub 2020 Dec 18.

Institute of Research on Musculoskeletal Disorders, Valencia Catholic University, Valencia, Spain.

Musculoskeletal functional deterioration in Amyotrophic lateral sclerosis (ALS) is associated with an increase in bone fractures. The purpose of this study was to evaluate the influence of sex, ALS type, on bone quality in patients with ALS compared to healthy controls. The impact on bone health of the clinical status and some metabolic parameters was also analyzed in ALS patients. A series of 33 voluntary patients with ALS, and 66 healthy individuals matched in sex and age underwent assessment of bone mass quality using quantitative ultrasound (QUS) of the calcaneus. Ultrasonic broadband attenuation (BUA), the speed of sound (SOS), stiffness index and -score were measured. Bone mineral density (BMD) was estimated using standard equations. Apart from fat and muscle mass percentage determinations, clinical baseline measures in ALS patients included ALSFRS-R score, Barthel index for activities of daily living, pulmonary function measured using FVC, and muscular strength assessed by a modified MRC grading scale. Laboratory tests included serum calcium, 25-HO-cholecalciferol (Vitamin D), alkaline phosphatase (ALP), T4 and TSH. All bone parameters evaluated were statistically significant lower in ALS patients than in healthy controls. ALS females showed significantly lower bone parameters than healthy females. According to the estimated BMD, there were 25 ALS patients (75.8%) and 36 (54.5%) healthy individuals showing an osteoporotic profile (BMD <0.700 g/cm). Only 16.7% of the ALS females had -scores indicative of healthy bones. There was no correlation between any of the clinical parameters analyzed and the bone QUS measurements. Vitamin D and TSH levels positively correlated with all the bone parameters. This study confirms that ALS patients, particularly females, exhibited deteriorated bone health as compared to healthy individuals. These structural bone changes were independent of ALS subtype and clinical status. Bone health in ALS patients seems to be related to certain metabolic parameters such as Vitamin D and TSH levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.599216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775537PMC
December 2020

Occupational risk factors for shoulder chronic tendinous pathology in the Spanish automotive manufacturing sector: a case-control study.

BMC Musculoskelet Disord 2020 Dec 7;21(1):818. Epub 2020 Dec 7.

Institute for Research on Musculoskeletal Disorders, School of Medicine and Health Sciences, Valencia Catholic University, Valencia, Spain.

Background: Musculoskeletal Diseases (MSDs) are among the most prevalent health problems encountered in the workforce in Europe. Multiple risk factors contribute to their onset. In the present study, different individual risk factors for chronic tendinous pathology affecting the shoulder were analysed in a sample of workers from the automotive manufacturing sector.

Methods: An observational retrospective study was conducted with 73 cases of officially recognised and compensated occupational diseases and 94 aleatory cases of healthy workers from the same car assembly company. The experimental group comprised individuals with tendinous chronic pathology of the rotator cuff. Multiple variables that identified the risks present in the job were assessed along with participants clinical evaluation. Furthermore, two standardised guidelines for risk factors assessment were also used: the Spanish National Institute of Social Security (INSS) and the American Occupational Information Network (O*Net). Both descriptive statistical analysis and Odds ratios calculations considering the occupational disease as a dependent variable were performed.

Results: The use of hand tools, exposure to mechanical pressure in the upper limbs and awkward postures were the most prevalent risk factors. Pressure on the palm of the hand and the hand tool impacting the hand were also important risk factors. Some psychosocial factors such as lack of autonomy and mental workload were also associated shoulder tendinous diseases. The association of age, load handling, and awkward postures were the core risk factors responsible for most of the tendinous chronic injuries of the shoulder in this sample of car assembly workers.

Conclusions: Both ergonomic and psychosocial factors were present and increased the risk of developing occupational chronic tendinopathies at the shoulder in this sample of workers. Aging, load handling, and awkward postures showed the strongest predictive values. Greater knowledge of how risk factors interact would facilitate the design of better preventive workplace strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-020-03801-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722306PMC
December 2020

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.

Lancet 2020 12;396(10265):1817-1828

Barts Cancer Institute, Centre for Experimental Cancer Medicine and Queen Mary University of London, London, UK.

Background: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer.

Methods: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine-carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at this interim analysis; follow-up to assess overall survival is continuing. For progression-free survival, a hierarchical testing strategy was used, such that testing was done first in patients with CPS of 10 or more (prespecified statistical criterion was α=0·00411 at this interim analysis), then in patients with CPS of 1 or more (α=0·00111 at this interim analysis, with partial alpha from progression-free survival in patients with CPS of 10 or more passed over), and finally in the intention-to-treat population (α=0·00111 at this interim analysis). This study is registered with ClinicalTrials.gov, NCT02819518, and is ongoing.

Findings: Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab-chemotherapy group and 281 patients in the placebo-chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8-29·9) in the pembrolizumab-chemotherapy group and 26·3 months (22·7-29·7) in the placebo-chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab-chemotherapy and 5·6 months with placebo-chemotherapy (hazard ratio [HR] for progression or death, 0·65, 95% CI 0·49-0·86; one-sided p=0·0012 [primary objective met]). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61-0·90; one-sided p=0·0014 [not significant]) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69-0·97 [not tested]) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment. Grade 3-5 treatment-related adverse event rates were 68% in the pembrolizumab-chemotherapy group and 67% in the placebo-chemotherapy group, including death in <1% in the pembrolizumab-chemotherapy group and 0% in the placebo-chemotherapy group.

Interpretation: Pembrolizumab-chemotherapy showed a significant and clinically meaningful improvement in progression-free survival versus placebo-chemotherapy among patients with metastatic triple-negative breast cancer with CPS of 10 or more. These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic triple-negative breast cancer.

Funding: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)32531-9DOI Listing
December 2020

Mentoring as an opportunity to improve research and cancer care in Latin America (AAZPIRE project).

ESMO Open 2020 11;5(6):e000988

Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogota, Colombia. Electronic address:

Effective networking and mentoring are critical determinants of professional satisfaction and success in oncology. There are multiple benefits associated with established mentoring programs. However, these are scarce in Latin America (LATAM). The AAZPIRE project meeting was held to encourage the discussion of mentorship strategies in our region, to create new learning frameworks, and improve cancer care. A group of 30 young oncologists and investigators, together with seven members of LACOG and CLICaP experts of 8 LATAM countries, were reunited to share views and define opportunities, barriers, and possible solutions to implement mentorship programs in LATAM. For each of the mentioned topics, key points were obtained by consensus, and a literature review was conducted to support group conclusions. This article analyses mentoring in LATAM countries and its role on promoting leadership. It will address conceptual frameworks, limitations, and opportunities from the perspectives of both mentor and mentee. The creation of regional and international group stimulation programs and joint projects that impact health policies are attractive, starting points to implement mentorship scenarios.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/esmoopen-2020-000988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689104PMC
November 2020

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial.

Clin Breast Cancer 2021 Feb 6;21(1):80-91.e7. Epub 2020 Oct 6.

Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, GEICAM, Universidad Complutense, Madrid, Spain.

Background: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2)/hormone receptor-positive (HR) early-stage breast cancer (eBC).

Patients And Methods: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2 eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR eBC who initiated treatment ≤ 1 year (HR/≤ 1-year) and > 1 year (HR/> 1-year) post-trastuzumab.

Results: HR/≤ 1-year and HR/> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR/≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR/>1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR/≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR/≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported.

Conclusion: Neratinib significantly improved iDFS in the HER2/HR/≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clbc.2020.09.014DOI Listing
February 2021

Changes in Salivary Levels of Creatine Kinase, Lactate Dehydrogenase, and Aspartate Aminotransferase after Playing Rugby Sevens: The Influence of Gender.

Int J Environ Res Public Health 2020 11 5;17(21). Epub 2020 Nov 5.

Institute for Research on Musculoskeletal Disorders, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain.

Rugby sevens is characterised by continuous exertion and great physical contact per unit of time, leading to muscle damage. It is important to identify markers that can quantify muscle damage in order to improve recovery strategies. The objective of this study was to evaluate the release dynamics of muscle damage markers creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in saliva samples when playing rugby sevens, analysing the influence of gender, during the rugby sevens university championship of Spain. The total sample included 27 athletes, divided into two teams of 14 men and 13 women between 18 and 31 years of age. CK, LDH, and AST were quantified from salivary samples collected from each athlete before and after three rugby sevens matches. The modified Borg scale of perceived exertion was also used after each match. When the results were analysed globally, there were no differences in CK and LDH before and after any match, but AST did show differences after two days of completing all matches. In terms of gender, the three enzymes showed different responses in men and women. Regarding the Borg scale, there were only significant differences between men and women after completing all mataches, with a greater perceived exertion in women. Based on our results, it can be stated that that serial matches of rugby sevens can cause changes of different magnitude in AST, CK and LDH activities in saliva, with AST showing the most significant variations and these changes are more pronounced in men than in women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17218165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663852PMC
November 2020

Efficacy and Safety of Anti-Interleukin-17A Monoclonal Antibody Secukinumab in Treatment of Ankylosing Spondylitis: A Meta-Analysis.

Monoclon Antib Immunodiagn Immunother 2020 Oct 1;39(5):160-166. Epub 2020 Oct 1.

Department of Neurosurgery, One Medical Center, Morgantown, West Virginia, USA.

Different signaling pathways have been studied in ankylosing spondylitis. New treatment options such as secukinumab could have an important role inhibiting the release of proinflammatory cytokine IL-17. The aim of this study was to compare the efficacy and safety of secukinumab in ankylosing spondylitis. A systematic review was conducted using MEDLINE and EMBASE databases to identify randomized clinical trials (RCTs) that assess the role of secukinumab in ankylosing spondylitis. The variables were safety (total adverse events, serious adverse events, headache, nasopharyngitis, cough, deaths, discontinuation due to adverse events, candida, neutropenia, and diarrhea) and efficacy based on quality-of-life scores (ASAS 20, ASAS 40, ASAS 5/6, ASASPR). Three RCTs (770 patients) that compare secukinumab with placebo were included in the study. There were significant differences in the quality-of-life scores in favor of the secukinumab group ( < 0.05). Regarding the adverse events, there were higher rates of any adverse events in the secukinumab group ( < 0.05). Also, the secukinumab group showed a higher rate of nasopharyngitis and diarrhea ( < 0.05). The use of secukinumab in ankylosing spondylitis increased the quality of life and had more adverse events rate compared with placebo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/mab.2020.0022DOI Listing
October 2020

Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC.

N Engl J Med 2020 10;383(14):1328-1339

From the Yale School of Medicine, New Haven, CT (R.S.H.); Weill Cornell Medical Center, New York (G.G.); the European Institute of Oncology, IRCCS, Milan (F.M.); Asklepios Lung Clinic, Munich-Gauting, Germany (N.R.); University Hospital Limoges, Limoges, France (A.V.); Centro de Pesquisa Clínica, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil (C.H.B.); Nagoya University Graduate School of Medicine, Aichi, Japan (M. Morise); Vall d'Hebron University Hospital, Barcelona (E.F.); Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia (Z.A.); Prince of Songkla University-Hat Yai, Songkhla, Thailand (S.G.); Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey (M.O.); Genentech, South San Francisco, CA (W.Z., A.S., I.E., K.K., Y.D., H.K., X.W., M. McCleland, S.M.); the Medical University of Gdańsk, Gdansk, Poland (J.J.); and the Sarah Cannon Research Institute at Tennessee Oncology, Nashville (D.R.S.).

Background: The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC) with PD-L1 expression are not known.

Methods: We conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with respect to mutations or translocations. Within the population with and wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden.

Results: Overall, 572 patients were enrolled. In the subgroup of patients with and wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01). Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups. Overall and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden.

Conclusions: Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. (Funded by F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1917346DOI Listing
October 2020

Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial.

Lancet 2020 10 20;396(10257):1090-1100. Epub 2020 Sep 20.

Breast Center, Department of Gynecology and Obstetrics and Comprehensive Cancer Center of the Ludwig-Maximilians-University, Munich, Germany.

Background: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC.

Methods: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m every week for 12 weeks followed by doxorubicin at 60 mg/m and cyclophosphamide at 600 mg/m every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing.

Findings: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group).

Interpretation: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile.

Funding: F Hoffmann-La Roche/Genentech.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)31953-XDOI Listing
October 2020

Pressure Sensitive Adhesive Tape: A Versatile Material Platform for Optical Sensors.

Sensors (Basel) 2020 Sep 16;20(18). Epub 2020 Sep 16.

Institute for Optoelectronic Systems and Microtechnology (ISOM), ETSI Telecomunicación, Universidad Politécnica de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.

Pressure sensitive adhesive (PSA) tapes are a versatile, safe and easy-to-use solution for fastening, sealing, masking, or joining. They are widely employed in daily life, from domestic use to industrial applications in sectors such as construction and the automotive industry. In recent years, PSA tapes have found a place in the field of micro- and nanotechnology, particularly in contact transfer techniques where they can be used as either sacrificial layers or flexible substrates. As a consequence, various optical sensing configurations based on PSA tapes have been developed. In this paper, recent achievements related to the use of PSA tapes as functional and integral parts of optical sensors are reviewed. These include refractive index sensors, optomechanical sensors and vapor sensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s20185303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570651PMC
September 2020

Lack of access to CDK4/6 inhibitors for premenopausal patients with metastatic breast cancer in Brazil: estimation of the number of premature deaths.

Ecancermedicalscience 2020 30;14:1081. Epub 2020 Jul 30.

Latin American Cooperative Oncology Group (LACOG), Porto Alegre, 90619-900, Brazil.

Purpose: A CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy is the standard of care for patients with hormone receptor-positive (HR+) and HER2-negative (HER2-) metastatic breast cancer (MBC). However, the incorporation of these agents into clinical practice remains challenging. This study aims to estimate the impact of the lack of access to ribociclib on mortality of premenopausal patients with MBC in Brazil.

Methods: Based on published epidemiological studies and national cancer registries, we estimated the number of premenopausal patients with potential indication of ribociclib as first-line treatment for MBC. Efficacy estimates were based on results from the Monaleesa-7 trial. Our analysis is made under the unrealistic assumption that all premenopausal MBC patients would be candidates for the treatment. To estimate the number of yearly premature deaths that could be prevented, we considered the largest absolute effect on mortality when sequentially applying the observed hazard ratio.

Results: We estimated an annual incidence of 4,294 premenopausal HR+, HER2- MBC patients in Brazil. Considering these patients, at 12, 24 and 60 months, the number of surviving subjects would be 3,504, 2,859 and 1,553 for endocrine therapy (ET) alone; and 3,717, 3,217 and 2,086 for ET plus ribociclib. The largest difference between both groups was observed at the end of the sixth year when the use of ribociclib would prevent 538 premature deaths (survival of 1,805 versus 1,267 patients by the 72nd month).

Conclusion: We estimate that lack of access to CDK4/6i for patients with HR+, HER2-, MBC will cause the premature death of a significant number of premenopausal women with MBC. The unavailability of effective therapies has measurable consequences. Progress in this area demands a concerted effort to prevent further loss of lives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3332/ecancer.2020.1081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434502PMC
July 2020

The impact of sociodemographic factors and health insurance coverage in the diagnosis and clinicopathological characteristics of breast cancer in Brazil: AMAZONA III study (GBECAM 0115).

Breast Cancer Res Treat 2020 Oct 29;183(3):749-757. Epub 2020 Jul 29.

Hospital Israelita Albert Einstein, São Paulo, Brazil.

Purpose: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type.

Methods: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured.

Results: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001).

Conclusions: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-05831-yDOI Listing
October 2020

Efficacy of eribulin for metastatic breast cancer based on localization of specific secondary metastases: a post hoc analysis.

Sci Rep 2020 07 8;10(1):11203. Epub 2020 Jul 8.

Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.

Prior pooled analysis of eribulin studies (301 and 305) indicated eribulin prolonged overall survival (OS) in patients with locally advanced/metastatic breast cancer (MBC) regardless of visceral or nonvisceral disease. This hypothesis-generating post hoc analysis examined the efficacy of eribulin according to the location of metastatic sites at baseline in 1864 pretreated patients with locally advanced/MBC from studies 301 and 305. Analyses included OS, progression-free survival (PFS), and objective response rate; OS and PFS were also analyzed according to estrogen-receptor status. Eribulin appeared efficacious in patients with locally advanced/MBC, irrespective of the location of metastases at baseline. A nominally significant difference in OS in favor of patients randomized to eribulin compared with control in patients with bone, lymph node, and chest wall/breast/skin metastases at baseline was observed. Additionally, a difference in OS was also seen in patients with liver metastases randomized to eribulin versus control (median: 13.4 versus 11.3 months, respectively; hazard ratio, 0.84 [95% CI: 0.72, 0.97]). Results of this exploratory analysis suggest that eribulin may be efficacious for the treatment of locally advanced/MBC for patients with bone, liver, lung, lymph node, and chest wall/breast/skin metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-66980-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343788PMC
July 2020

Localization and distribution of CCK-8, NPY, Leu-ENK-, and Ghrelin- in the digestive tract of Prochilodus lineatus (Valenciennes, 1836).

An Acad Bras Cienc 2020 12;92(2):e20181165. Epub 2020 Jun 12.

Instituto de Ictiología del Nordeste, Facultad de Ciencias Veterinarias, UNNE, Sargento Cabral 2139, Corrientes (3400), Argentina.

This study describes the histological characteristics and distribution of gastrointestinal tract endocrine cells (ECs) of Prochilodus lineatus (detritivorous fish) using immunohistochemical procedures. The digestive tract of P. lineatus was divided into seven portions: stomach (cardial and pyloric), pyloric caeca, and intestine (anterior, glandular, middle and posterior). A pool of specific antisera against cholecystokinin (CCK-8), -neuropeptide Y (NPY), -ghrelin (Ghre) and -leu-enkephalin (Leu-ENK) to identify ECs were used. According to the morphological characteristics of ECs, two different types were identified and classified as open or closed-type. The number of ECs varied throughout the gastrointestinal tract, though a high abundance was found in the anterior intestine and pyloric caeca. A large number of ECs immunoreactive to CCK-8 and NPY were recorded in the anterior, glandular and middle intestine. ECs immunopositive to Leu-ENK were distributed in the stomach and pyloric caeca. For Ghre, immunopositive ECs were restricted to the glandular intestine. The results of the present study indicate that P. lineatus presents an ECs distribution pattern with species-specific particularities. However, CCK showed a distribution similar to that of omnivores, which is possibly related to local signaling functions in order to achieve the correct digestion of the various organisms found in the detritus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0001-3765202020181165DOI Listing
June 2020

Validation of the concavity-convexity quotient as a new method to measure the magnitude of scoliosis.

J Craniovertebr Junction Spine 2020 Jan-Mar;11(1):31-35. Epub 2020 Apr 4.

Department of Orthopedic Surgery, University and Polytechnic La Fe Hospital, Valencia, Spain.

Objectives: We propose a novel and simple method to determine the magnitude of the curve in scoliosis and its correlation with the Cobb angle.

Methods: Using multiple rounds of nominal group technique and an established consensus-building methodology, a multidisciplinary research group identified a simple method to value the curve deformity based on the vertebral pedicles.

Measurements: A mathematical study was performed to determine the relationship between the Cobb angle and the concavity-convexity quotient (CCQ). To evaluate the clinical correlation between the Cobb angle and CCQ, spine surgeons measured 48 curves (before and after follow-up) of congenital scoliosis.

Results: This quotient reflects the ratio between the distance from the upper end of the most inclined upper vertebra to the lower end of the most inclined lower vertebra on the concave side (A-distance) and the corresponding distance on the convex side of the curve (B-distance). The existing mathematical relationship is based on changing the explicit coordinates to polar coordinates. Finally, the clinical correlation between the Cobb angle and CCQ was statistically significant ( = -0.688; < 0.001 in first measure and = -0.789; < 0.001 in the second measure).

Conclusions: Our study provides Level III evidence that CCQ represents a promising alternative or a complementary method to the traditional Cobb angle due to its simple and reliable ability to measure the magnitude of the curve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jcvjs.JCVJS_22_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274366PMC
April 2020

Accuracy of t-EMG stimulation of the middle pedicle track to prevent radiculopathies as a result of misplaced lumbar screws.

Clin Neurol Neurosurg 2020 Aug 19;195:105915. Epub 2020 May 19.

Institute for Research on Musculoskeletal Disorders, Valencia Catholic University, 46001 Valencia, Spain. Electronic address:

Objective: To describe the accuracy of middle pedicle track stimulation for the detection of pedicle breaches causing misplaced lumbar screws and subsequent neurological symptoms.

Patients And Methods: In a comparative observational study with two cohorts, 1440 lumbar pedicle screws were implanted using the freehand technique in 242 patients undergoing surgery for spinal deformities. In the first two-year period (2011-2012), the accuracy of screw placement (802 screws) was assessed by conventional intraoperative palpation of the pedicle track, t-EMG screw stimulation, and fluoroscopic monitoring. In the second period (2012-2013), the middle aspect of the lumbar pedicle tracks was systematically stimulated with a probe (638 screws). When thresholds in the middle track showed <9 mA, potential neurological risk was considered, and therefore, new pedicle tracks were performed.

Results: Six patients (4.4 %) in the first period presented postoperative radicular pain and a normal intraoperative screw t-EMG threshold. CT scans showed seven screws (0.9 %) with >2-mm medial-caudal invasion of the foramen. Before screw removal, t-EMG thresholds of these screws were again normal (≥10 mA). After removal of the screws. t-EMG of the middle part of the pedicle track showed thresholds below 9 mA (mean 5.2 mA). In the second period, the pedicle tracks were systematically stimulated. Low t-EMG thresholds (<9 mA) were found in 11 tracks (1.7 %) and were therefore reworked before screw placement. CT scans in these 10 patients showed that all of the 11 screws were correctly repositioned.

Conclusions: This study shows that caudal or medial pedicle cortical breaches can be detected effectively by stimulating the middle part of the pedicle track. This technique is strongly recommended to prevent postoperative lumbar radiculopathies due to screw malposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clineuro.2020.105915DOI Listing
August 2020

Real-World Prevalence of PD-L1 Expression Among Tumor Samples From Patients With Non-Small-Cell Lung Cancer.

Clin Lung Cancer 2020 11 13;21(6):e511-e515. Epub 2020 Apr 13.

Grupo Brasileiro de Oncologia Torácica, Porto Alegre, Brazil; Américas Centro de Oncologia, Rio De Janeiro, Brazil.

Introduction: We analyzed the prevalence of non-small-cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥ 50% and compared the results with the existing data from clinical trials and databases from other countries.

Materials And Methods: The Latin American Cooperative Oncology Group and Grupo Brasileiro de Oncologia Torácica performed a retrospective, cross-sectional study from August 2017 to April 2018. PD-L1 expression was collected from pathology reports from 5 laboratories in Brazil. All tests were sponsored by the pharmaceutical industry on request from the treating medical oncologist. PD-L1 expression was assessed by immunohistochemistry. The variables were summarized as absolute and relative frequencies or the median and interquartile range. Pearson's χ test was used to compare the TPS categories stratified by sex, age, and histologic type. All analyses were performed with SAS, version 9.4, and were deemed statistically significant at P < .05.

Results: A total of 1512 patients were included in the present study. Their median age was 66 years. Most patients were men (56.02%), and the most common histologic type was adenocarcinoma (58.04%); 109 tumors (11.31%) had EGFR mutations and 34 (3.64%) had ALK gene rearrangements. Overall, 56.54% had a PD-L1 TPS < 1%, 25.63% a TPS of 1% to 49%, and 17.83% a TPS of ≥ 50%. The factors associated with PD-L1 expression were histologic type (with adenocarcinoma samples having a greater proportion of TPS < 1%) and the laboratory that performed the test.

Conclusion: The prevalence of high PD-L1 expression among the Brazilian NSCLC samples was lower than previously described in other countries, which could affect the number of patients who might be candidates for immunotherapy alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2020.04.007DOI Listing
November 2020

Reply to Y. Usui et al.

J Clin Oncol 2020 06 30;38(18):2113-2114. Epub 2020 Apr 30.

Ana Lluch, PhD, Hospital Clínico Universitario de Valencia, Valencia; Biomedical Research Institute INCLIVA, University of Valencia, Valencia; Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid; and GEICAM, Spanish Breast Cancer Group, Madrid, Spain; Carlos H. Barrios, MD, Centro de Pesquisa Clínica Hospital São Lucas da PUCRS; and LACOG, Latin American Cooperative Oncology Group, Porto Alegre, Brazil, Laura Torrecillas, MD, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Ciudad de México, México; and Miguel Martín, MD, PhD, Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII; GEICAM, Spanish Breast Cancer Group; and Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.00390DOI Listing
June 2020

Mutations Are Not a Common Mechanism of Endocrine Resistance in Patients With Estrogen Receptor-Positive Breast Cancer Treated With Neoadjuvant Aromatase Inhibitor Therapy.

Front Oncol 2020 3;10:342. Epub 2020 Apr 3.

Postgraduate Program in Medical Sciences, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil.

Mutations in the gene (m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive (ER+) metastatic breast cancer and have been studied as a potential therapeutic target, as well as a predictive and prognostic biomarker. Nonetheless, the role of m as a possible mechanism of primary endocrine resistance, as well as whether it also occurs in tumors that are resistant to ET administered in early-stage disease as (neo)adjuvant, has not been adequately studied. In this study, we evaluated the prevalence of m in tumor samples from patients with ER+ breast cancer resistant to neoadjuvant aromatase inhibitor therapy. We followed a prospective cohort of patients with ER+ HER2- stages II and III breast cancer treated with neoadjuvant endocrine therapy (NET). Tumor samples from patients with a pattern of primary endocrine resistance [defined as a Preoperative Endocrine Prognostic Index (PEPI) score of ≥4] were identified and analyzed for the presence of m. One hundred twenty-seven patients were included in the cohort, of which 100 (79%) had completed NET and underwent surgery. Among these patients, the PEPI score ranged from 0 to 3 in 70% (70/100), whereas 30% (30/100) had a PEPI score of 4 or more. Twenty-three of these patients were included in the analysis. mutations were not identified in any of the 23 patients with early-stage ER+ breast cancer resistant to NET. Growing evidence supports the notion that there are different mechanisms for primary and secondary endocrine resistance. Our study suggests that mutations do not evolve rapidly and do not represent a common mechanism of primary endocrine resistance in the neoadjuvant setting. Therefore, m should be considered a mechanism of acquired endocrine resistance in the context of advanced disease. Further research should be conducted to identify factors associated with intrinsic resistance to ET.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145981PMC
April 2020