Circulating microRNAs as potential biomarkers in triple-negative breast cancer: a translational research study of the NACATRINE trial.

Liquid biopsy is increasingly vital in monitoring neoadjuvant breast cancer treatment. This study collected plasma samples at three time points from participants in the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE), analyzing miRNA expression with NanoString's nCounter® Human v3 miRNA assay. In the carboplatin arm, four ct-miRNAs exhibited dynamic changes linked to pathologic complete response, with a combined area under the curve of 0.811. Similarly, the non-carboplatin arm featured four ct-miRNAs with an area under the curve of 0.843. These findings underscore the potential of ct-miRNAs as personalized tools in breast cancer treatment, assisting in predicting treatment response and assessing the risk of relapse. Integrating ct-miRNA analysis into clinical practice can optimize decisions and enhance patient outcomes.

Neoadjuvant carboplatin in triple-negative breast cancer: results from NACATRINE, a randomized phase II clinical trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is the mainstay of treatment of stages II and III triple-negative breast cancer (TNBC). This study aims to evaluate if the addition of carboplatin to NACT is associated with an increase in the pathological complete response (pCR) rates in TNBC. METHODS: We conducted an open-label phase II randomized clinical trial in a single center in Brazil. Patients with stage II and III TNBC were randomized to receive standard NACT with or without carboplatin. All the patients received doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) both intravenously (i.v.) q21 days for four cycles. Patients were then randomized for additional treatment with weekly (wk) paclitaxel (80 mg/m2 i.v., for 12 cycles) plus wk carboplatin AUC 1.5 (experimental arm) or without wk carboplatin (control arm). Randomization was stratified according to gBRCA status, age, and AJCC 8th edition clinical stage (II vs. III). The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints included recurrence-free survival and overall survival. RESULTS: Between 2017 and 2021, 146 patients were randomized, 73 on each arm. The median age was 45 years. Most patients (66.4%) had locally advanced stage III disease, 67.1% had T3/T4 tumors, and 56.2% had clinically positive axillary lymph nodes. Germline BRCA status was available for all patients, and 19.9% had pathogenic BRCA1/2 variants. The pCR rate (ypT0ypN0) was numerically increased by 13.7%, being 43.8% (31 of 73 patients) in the experimental and 30.1% (22 of 73 patients) in the control arm, not meeting the prespecified goal of increasing the pCR in 15% (p-value = 0.08). Survival outcomes are immature. CONCLUSION: The addition of carboplatin to standard NACT in stages II and III TNBC was associated with a non-statistically significant numerical increase in the pCR rate. Follow-up for survival outcomes and translational research initiatives are ongoing.

Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer.

Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.

Whole-exome sequencing of non-BRCA1/BRCA2 mutation carrier cases at high-risk for hereditary breast/ovarian cancer.

The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer-related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high-risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.

Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial.

BACKGROUND: Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). MATERIALS AND METHODS: NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered. RESULTS: Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41-1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59-1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. CONCLUSION: These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC. IMPLICATIONS FOR PRACTICE: In a subgroup of patients with central nervous system (CNS) metastases from HER2-positive breast cancer after two or more previous HER2-directed regimens, the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2-positive brain metastases following antibody-based HER2-directed therapies.

Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta-analysis.

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.

Impact of the addition of cocoa butter equivalent on the volatile compounds profile of dark chocolate.

The effect of the partial replacement of cocoa butter (CB) by cocoa butter equivalent (CBE) in the release of volatile compounds in dark chocolate was studied. The fatty acid profile, triacylglyceride composition, solid fat content (SFC) and melting point were determined in CB and CBE. Chocolate with CB (F1) and with different content of CBE (5 and 10%-F2 and F3, respectively) were prepared. Plastic viscosity and Casson flow limit, particle size distribution and release of volatile compounds using a solid phase microextraction with gas chromatography (SMPE-GC) were determined in the chocolate samples. The melting point was similar for the studied samples but SFC indicated different melting behavior. CBE showed a higher saturated fatty acid content when compared to CB. The samples showed similar SOS triglyceride content (21 and 23.7% for CB and CBE, respectively). Higher levels of POS and lower POP were observed for CB when compared to CBE (44.8 and 19.7 and 19 and 41.1%, respectively). The flow limit and plastic viscosity were similar for the studied chocolates samples, as well as the particle size distribution. Among the 27 volatile compounds identified in the samples studied, 12 were detected in significantly higher concentrations in sample F1 (phenylacetaldehyde, methylpyrazine, 2,6-dimethylpyrazine, 2-ethyl-5-methylpyrazine, 2-ethyl-3,5-dimethylpyrazine, tetramethylpyrazine, trimethylpyrazine, 3-ethyl-2,5-dimethylpyrazine, phenethyl alcohol, 2-acetylpyrrole, acetophenone and isovaleric acid). The highest changes were observed in the pyrazines group, which presented a decrease of more than half in the formulations where part of the CB was replaced by the CBE.

Tissue characterization and phenotype classification in patients presenting with acute myocardial infarction: Insights from the iWonder study.

OBJECTIVES: We sought to assess a new modality of radiofrequency intravascular ultrasound (IVUS) called iMAP-IVUS (Boston Scientific, Santa Clara, California) during the evaluation of patients presenting with high-risk acute coronary syndromes. BACKGROUND: There are limited data on plaque tissue characterization and phenotype classification using iMAP-IVUS. METHODS: In the iWonder study patients presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI underwent three-vessel grayscale IVUS and iMAP-IVUS tissue characterization prior to percutaneous intervention. In total 385 lesions from 100 patients were divided into culprit (n = 100) and nonculprit (n = 285) lesions. Lesion phenotype was classified as (i) thin-cap fibroatheroma (iMAP-derived TCFA); (ii) thick-cap fibroatheroma; (iii) pathological intimal thickening; (iv) fibrotic plaque; and (v) fibrocalcific plaque. RESULTS: Culprit lesions had smaller minimum lumen cross-sectional area (MLA) with greater plaque burden compared to non-culprit lesions. Volumetric analysis showed that culprit lesions had longer length and larger vessel and plaque volumes compared to non-culprit lesions. iMAP-IVUS revealed that culprit lesions presented more NC and fibrofatty volume, both at lesion level and at the MLA site (all P < 0.001). Any fibroatheroma was more frequently identified in culprit lesions compared with non-culprit lesions (93% vs. 78.9%, P = 0.001), anywhere within the lesion 19.0%, P < 0.001) as well as at the MLA site (18.0% vs. 9.5%, P = 0.07). CONCLUSIONS: Three-vessel radiofrequency iMAP-IVUS demonstrated a greater plaque burden and higher prevalence of any fibroatheroma as well as iMAP-derived TCFAs in culprit versus non-culprit lesions in patients presenting with STEMI or non-STEMI undergoing percutaneous coronary intervention. © 2017 Wiley Periodicals, Inc.

Oncogenetics service and the Brazilian public health system: the experience of a reference Cancer Hospital.

The identification of families at-risk for hereditary cancer is extremely important due to the prevention potential in those families. However, the number of Brazilian genetic services providing oncogenetic care is extremely low for the continental dimension of the country and its population. Therefore, at-risk patients do not receive appropriate assistance. This report describes the creation, structure and management of a cancer genetics service in a reference center for cancer prevention and treatment, the Barretos Cancer Hospital (BCH). The Oncogenetics Department (OD) of BCH offers, free of charge, to all patients/relatives with clinical criteria, the possibility to perform i) genetic counseling, ii) preventive examinations and iii) genetic testing with the best quality standards. The OD has a multidisciplinary team and is integrated with all specialties. The genetic counseling process consists (mostly) of two visits. In 2014, 614 individuals (371 families) were seen by the OD. To date, over 800 families were referred by the OD for genetic testing. The support provided by the Oncogenetics team is crucial to identify at-risk individuals and to develop preventive and personalized behaviors for each situation, not only to the upper-middle class population, but also to the people whose only possibility is the public health system.

The Functionality Assessment Flowchart (FAF): a new simple and reliable method to measure performance status with a high percentage of agreement between observers.

BACKGROUND: Performance status (PS) assessment is an integral part of the decision-making process in cancer care. Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) PS are the most widely used tools. In some studies, the absolute agreement rate of these tools between observers has been moderate to low. The present study aimed to evaluate the inter-observer reliability and construct validity of the new Functionality Assessment Flowchart (FAF) and compare it with ECOG PS and KPS in a sample of cancer patients. METHODS: The patients were recruited by convenience from the waiting rooms of the Breast and Gynecology Ambulatory in a cross-sectional study. Two trained medical students (observer A) and five medical oncologists (observers B) independently rated women according to the ECOG PS, KPS and FAF. After the determining the PS scores, observer A administered the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire to the participants. The agreements between observers A and B were investigated using the absolute agreement rate (%), weighted and unweighted kappa and Spearman's correlation test. For construct validity, the PS scores were correlated with functional and fatigue scores by performing correlation analysis. RESULTS: Eighty women with a median age of 57 years were included in the study (86% accrual rate). Among these women, 39 (48.8%) had advanced cancer. The overall absolute agreement rate between observers was 49.4% for KPS, 67% for ECOG PS, and 78.2% for FAF. When using unweighted kappa values, the inter-observer reliability was "fair", "moderate" and "substantial" for KPS, ECOG PS and FAF, respectively. However, when using weighted kappa statistics, "substantial" agreement was observed for KPS and ECOG PS and "nearly perfect" agreement was observed for FAF. All of the PS scales correlated very well with the functional and fatigue scores. CONCLUSIONS: We present a new instrument with moderate to high inter-observer agreement and adequate construct validity to measure PS in cancer patients.

A critical analysis of test-retest reliability in instrument validation studies of cancer patients under palliative care: a systematic review.

BACKGROUND: Patient-reported outcome validation needs to achieve validity and reliability standards. Among reliability analysis parameters, test-retest reliability is an important psychometric property. Retested patients must be in a clinically stable condition. This is particularly problematic in palliative care (PC) settings because advanced cancer patients are prone to a faster rate of clinical deterioration. The aim of this study was to evaluate the methods by which multi-symptom and health-related qualities of life (HRQoL) based on patient-reported outcomes (PROs) have been validated in oncological PC settings with regards to test-retest reliability. METHODS: A systematic search of PubMed (1966 to June 2013), EMBASE (1980 to June 2013), PsychInfo (1806 to June 2013), CINAHL (1980 to June 2013), and SCIELO (1998 to June 2013), and specific PRO databases was performed. Studies were included if they described a set of validation studies. Studies were included if they described a set of validation studies for an instrument developed to measure multi-symptom or multidimensional HRQoL in advanced cancer patients under PC. The COSMIN checklist was used to rate the methodological quality of the study designs. RESULTS: We identified 89 validation studies from 746 potentially relevant articles. From those 89 articles, 31 measured test-retest reliability and were included in this review. Upon critical analysis of the overall quality of the criteria used to determine the test-retest reliability, 6 (19.4%), 17 (54.8%), and 8 (25.8%) of these articles were rated as good, fair, or poor, respectively, and no article was classified as excellent. Multi-symptom instruments were retested over a shortened interval when compared to the HRQoL instruments (median values 24 hours and 168 hours, respectively; p = 0.001). Validation studies that included objective confirmation of clinical stability in their design yielded better results for the test-retest analysis with regard to both pain and global HRQoL scores (p < 0.05). The quality of the statistical analysis and its description were of great concern. CONCLUSION: Test-retest reliability has been infrequently and poorly evaluated. The confirmation of clinical stability was an important factor in our analysis, and we suggest that special attention be focused on clinical stability when designing a PRO validation study that includes advanced cancer patients under PC.

Steroid-induced ocular hypertensive response in children and adolescents with acute lymphoblastic leukemia and non-Hodgkin lymphoma.

The aim of this study was to evaluate intraocular pressure (IOP) associated with use of glucocorticoids in children and adolescents treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma. We carried out a prospective descriptive study with measurement of IOP before treatment (D0), 8th (D8), 14th (D14), and 28 h days (D28) of treatment. We examined 12 patients, with two cases of ocular hypertension, and it was found a statistically significant difference between the means of IOP between D0 versus D8 and D0 versus D14 (P = 0.013). The possibility of silent ocular hypertension with irreversible blindness indicates the need of IOP verification.

Antibody-Drug Conjugates in Breast Cancer: A Comprehensive Review of How to Selectively Deliver Payloads.

Antibody-drug conjugates (ADCs) have surfaced as a promising group of anticancer agents employing the precise targeting capacity of monoclonal antibodies to transport highly effective cytotoxic payloads. Compared to conventional chemotherapy, they aim to selectively eradicate cancer cells while minimizing off-target toxicity on healthy tissues. An increasing body of evidence has provided support for the efficacy of ADCs in treating breast cancer across various contexts and tumor subtypes, resulting in significant changes in clinical practice. Nevertheless, unlocking the full potential of these therapeutic agents demands innovative molecular designs to address complex clinical challenges, including drug resistance, tumor heterogeneity, and treatment-related adverse events. This thorough review provides an in-depth analysis of the clinical data on ADCs, offering crucial insights from pivotal clinical trials that assess the efficacy of ADCs in diverse breast cancer settings. This aids in providing a comprehensive understanding of the current state of ADCs in breast cancer therapy, while also providing valuable perspectives for the future.

A pilot study addressing the impact of religious practice on quality of life of breast cancer patients during chemotherapy.

The aim of this preliminary study was to investigate whether religious practice can modify quality of life (QoL) in BC patients during chemotherapy. QoL and religion practice questionnaire (RPQ) scores were evaluated in a sample of BC patients in different moments. Before chemotherapy initiation, women with lower physical and social functional scores displayed higher RPQ scores. On the other hand, low RPQ patients worsened some QoL scores over time. Body image acceptance was positively correlated with religious practice and specifically praying activity. This preliminary study suggests the importance of religion in coping with cancer chemotherapy.

Molecular Biology of Pediatric and Adult Ovarian Germ Cell Tumors: A Review.

Ovarian germ cell tumors (OGCTs) are rare in adults; indeed, they occur predominantly in children, adolescents, and young adults, and they account for approximately 11% of cancer diagnoses in these groups. Because OGCTs are rare tumors, our current understanding of them is sparse; this is because few studies have investigated the molecular basis of pediatric and adult cancers. Here, we review the etiopathogenesis of OGCTs in children and adults, and we address the molecular landscape of these tumors, including integrated genomic analysis, microRNAs, DNA methylation, the molecular implications of treatment resistance, and the development of in vitro and in vivo models. An elucidation of potential molecular alterations may provide a novel field for understanding the pathogenesis, tumorigenesis, diagnostic markers, and genetic peculiarity of the rarity and complexity of OGCTs.

Gene expression alterations predict the pathological complete response in triple-negative breast cancer exploratory analysis of the NACATRINE trial.

This exploratory analysis of the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE) study aimed to identify the biomarkers of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC) within the context of a clinical trial. The NACATRINE trial is a phase II, single-center, randomized, open-label clinical trial that investigated the addition of carboplatin to sequential anthracycline- and taxane-based NAC for TNBC. We evaluated the gene expression in untreated samples to investigate its association with pCR, overall survival (OS), and disease-free survival (DFS). RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel was used to analyze gene expression. Of the 66 patients included in the gene expression profiling analysis, 24 (36.4%) achieved pCR and 42 (63.6%) had residual disease. In unsupervised hierarchical clustering analyses, differentially expressed genes between patients with and without pCR were identified irrespective of the treatment (24 genes), carboplatin (37 genes), and non-carboplatin (27 genes) arms. In receiver operating characteristic (ROC) curve analysis, 10 genes in the carboplatin arm (area under the ROC curve [AUC], 0.936) and three genes in the non-carboplatin arm (AUC, 0.939) were considered to be potential pCR-associated biomarkers. We identified genes that were associated with improvements in OS and DFS in addition to being related to pCR. We successfully identified gene expression signatures associated with pCR in pretreatment samples of patients with TNBC treated with NAC. Further investigation of these biomarkers is warranted.

In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has demonstrated several clinical manifestations which include not only respiratory system issues but also liver, kidney, and other organ injuries. One of these abnormalities is coagulopathies, including thrombosis and disseminated intravascular coagulation. Because of this, the administration of low molecular weight heparin is required for patients that need to be hospitalized. In addition, Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome, Ebola, Acute Respiratory Syndrome, and other diseases, showing satisfactory results on recovery. Besides, there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19. AIM: To investigate in silico the interaction between Remdesivir and clotting factors, pursuing a possibility of using it as medicine. METHODS: In this in silico study, the 3D structures of angiotensin-converting enzyme 2 (ACE2), Factor I (fibrinogen), Factor II (prothrombin), Factor III (thromboplastin), Factor V (proaccelerin), Factor VII (proconvertin), Factor VIII (antihemophilic factor A), Factor IX (antihemophilic factor B), Factor X (Stuart-Prower factor), and Factor XI (precursor of thromboplastin (these structures are technically called receptors) were selected from the Protein Data Bank. The structures of the antivirals Remdesivir and Osetalmivir (these structures are called ligands) were selected from the PubChem database, while the structure of Atazanavir was selected from the ZINC database. The software AutoDock Tools (ADT) was used to prepare the receptors for molecular docking. Ions, peptides, water molecules, and other ones were removed from each ligand, and then, hydrogen atoms were added to the structures. The grid box was delimited and calculated using the same software ADT. A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors, and still the software Marvin sketch® (ChemAxon®) was used to forecast the protonation state. To perform molecular docking, ADT and Vina software was connected. Using PyMol® software and Discovery studio® software from BIOVIA, it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands. Ligand tortions, atoms that participated in the interactions, and the type, strength, and duration of the interactions were also analyzed using those software. RESULTS: Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of -8.8 kcal/moL, forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2. Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor. Similar to that, Remdesivir and thromboplastin presented interactions via seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor. While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor, and Factor VII connected with the drug by four hydrogen bonds, which involved three atoms of the drug and three residues of amino acids of the factor. The complex between Remdesivir and Factor IX formed an interaction via 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor, plus one electrostatic bond and three hydrophobic interactions. Factor X and Remdesivir had an affinity energy of -9.6 kcal/moL, and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor. The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms. CONCLUSION: Because of the in silico significant affinity, Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.

Evaluation of upper limb lymphoedema and diagnostic accuracy of bioimpedance spectroscopy. A comprehensive validation in a Brazilian population.

Lymphoedema is a complication of breast cancer treatment. Its early diagnosis is related to a good prognosis for lymphoedema treatment. The bioimpedance spectroscopy (BIS) evaluates changes in extracellular fluid. The objective of our study was to evaluate the validity, agreement and accuracy of BIS in the diagnosis of breast cancer-related lymphoedema in a Brazilian population. Methods: This is a prospective, cross-sectional study of a convenience sample of 462 women who underwent surgical treatment for breast cancer (mastectomy or breast-conserving treatment). The validity, agreement and accuracy were performed comparing BIS (lymphoedema index (L-DEX) ≥ 6.5 or 10) with volumetry by water displacement, which is the gold standard for evaluating lymphoedema. Receiver operating characteristic curve was performed. Additionally, other methods like perimetry and indirect volumetry of the upper limbs were compared with water displacement volumetry (direct volumetry), and the BIS were compared with subjective evaluation. Results: Considering L-DEX ≥ 10 the sensitivity of the BIS was 44.1%, specificity 95.4%, positive predictive value (PPV) was 70.7%, negative predictive value (NPV) was 87% and kappa was 0.459. The BIS with L-DEX ≥ 6.5, the sensitivity, specificity, PPV, NPV and kappa were 57%, 88.5%, 55.8%, 89% and 0.452, respectively. Area under curve was 0.724 and a possible cut-off point of L-DEX ≥ 7.35 with sensitivity of 57%, specificity of 90.7% and kappa value = 0.489. Conclusion: Although BIS was significantly associated with the subjective evaluation of lymphoedema, it showed low sensitivity and agreement and moderate correlation when used as a method for diagnosing the condition. Thus, it is not the most valid method for evaluating lymphoedema. In addition, it was not the most accurate method when compared with other objective evaluation tools. Public health resources are scarce and must be used consciously. The knowledge that BIS is not a more accurate method than other, lower-cost instruments allows for better targeting of these resources.

Discrepancies in breast cancer's oncological outcomes between public and private institutions in the southeast region of Brazil: a retrospective cohort study.

Background: Brazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers. Patient and methods: A retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital-BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups' characteristics (n = 137 in each group). Results: The median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41-3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16-6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service. Conclusion: Patients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM.

Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil.

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.