Limited Health Literacy Among Patients With Orthopedic Injuries: A Cross-sectional Survey of Patients Who Underwent Orthopedic Trauma Surgery in a County Hospital Setting.

BACKGROUND: Patients with limited health literacy have difficulty understanding their injuries and postoperative treatment, which can negatively affect their outcomes. MATERIALS AND METHODS: This cross-sectional questionnaire-based study of 103 adult patients sought to quantify patients' health literacy at a single county hospital's orthopedic trauma clinic and to examine their ability to understand injuries and treatment plans. Demographics, Newest Vital Sign (NVS) health literacy assessment, and knowledge scores were used to assess patients' comprehension of their injuries and treatment plan. Patients were grouped by NVS score (NVS <4: limited health literacy). Fisher's exact tests and t tests were used to compare demographic and comprehension scores. Multivariate logistic regression analysis was used to examine the association among low health literacy, sociodemographic variables, and knowledge scores. RESULTS: Of the 103 patients, 75% were determined to have limited health literacy. Patients younger than 30 years were more likely to have adequate literacy (50% vs 23%, P=.01). Patients who spoke Spanish as their primary language were 8.77 times more likely to have limited health literacy with respect to sociodemographic factors (odds ratio, 8.77; 95% CI, 1.03-76.92; P=.04). Low health literacy was 3.52 and 4.14 times more likely to predict discordance in answers to specific bone fractures and the narcotics prescribed (P=.04 and P=.02, respectively). CONCLUSION: Spanish-speaking patients have demonstrated limited health literacy and difficulty understanding their injuries and postoperative treatment plans compared with English-speaking patients. Patients with low health literacy are more likely to be unsure regarding which bone they fractured or their prescribed opiates. [Orthopedics. 202x;4x(x):xx-xx.].

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Intranasal administration of molecular-gated mesoporous nanoparticles to increase ponatinib delivery to the brain.

Background: Glioblastoma is the most common and lethal brain cancer. New treatments are needed. However, the presence of the blood-brain barrier is limiting the development of new treatments directed toward the brain, as it restricts the access and distribution of drugs to the CNS. Materials & methods: In this work, two different nanoparticles (i.e., mesoporous silica nanoparticles and magnetic mesoporous silica nanoparticles) loaded with ponatinib were prepared. Results & conclusion: Both particles were characterized and tested in vitro and in vivo, proving that they are not toxic for blood-brain barrier cells and they increase the amount of drug reaching the brain when administered intranasally in comparison with the results obtained for the free drug.

This article presents a couple of promising nanoparticles for the treatment of brain cancer. This research is interesting because the brain and spinal cord are protected by a membrane that prevents toxic substances from reaching them but also hinders the access of drugs. One type of particle has a magnet in its core, so it can be driven with another external magnet until it reaches target; the other type does not have a magnet but has a small size, which would allow it to cross the membrane mentioned above. These particles have been proven to be able to kill cancer cells and to reach the brain after been administered through the nose in a better way than the free drug.

Histopathology of the Mitral Valve Residual Leaflet in Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Mitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown. OBJECTIVES: The purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the valve. METHODS: Structural and immunohistochemical staining were performed on 22 residual leaflets excised as ancillary procedures during myectomy, and compared with 11 control leaflets from deceased patients with normal hearts. Structural components were assessed with hematoxylin and eosin, trichrome, and elastic stains. We stained for EPDCs, EPDC paracrine signaling, valvular interstitial cells, endocardial-to-mesenchymal transition, and cardiomyocytes. RESULTS: The residual leaflet was always at A2 segment and attached by slack, elongated and curlicued, myxoid chords. MV residual leaflets in OHCM were structurally disorganized, with expanded spongiosa and increased, fragmented elastic fibers compared with control leading edges. The internal collagenous fibrosa was attenuated and there was collagenous tissue overlying valve surfaces in HCM, with an overall trend toward decreased leaflet thickness (1.09 vs 1.47 mm, P = 0.08). No markers of primary cellular processes were identified. CONCLUSIONS: MV residual leaflets in HCM were characterized by histologic findings that were likely secondary to chronic hemodynamic stress and may further increase susceptibility to systolic anterior motion.

Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry.

PURPOSE: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. METHODS: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1-3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). RESULTS: A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003-10 (210), and GEICAM-2006-10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. CONCLUSIONS: This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. TRIAL REGISTRATION: ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.

Evaluation of Anti-Neuroinflammatory Activity of Isatin Derivatives in Activated Microglia.

Neuroinflammation plays a crucial role in the progression of Alzheimer's disease and other neurodegenerative disorders. Overactivated microglia cause neurotoxicity and prolong the inflammatory response in many neuropathologies. In this study, we have synthesised a series of isatin derivatives to evaluate their anti-neuroinflammatory potential using lipopolysaccharide activated microglia as a cell model. We explored four different substitutions of the isatin moiety by testing their anti-neuroinflammatory activity on BV2 microglia cells. Based on the low cytotoxicity and the activity in reducing the release of nitric oxide, pro-inflammatory interleukin 6 and tumour necrosis factor α by microglial cells, the N1-alkylated compound 10 and the chlorinated 20 showed the best results at 25 µM. Taken together, the data suggest that 10 and 20 are promising lead compounds for developing new neuroprotective agents.

Establishment and Validation of a New Co-Culture for the Evaluation of the Permeability through the Blood-Brain Barrier in Patients with Glioblastoma.

Currently, the mechanisms involved in drug access to the central nervous system (CNS) are not completely elucidated, and research efforts to understand the behaviour of the therapeutic agents to access the blood-brain barrier continue with the utmost importance. The aim of this work was the creation and validation of a new in vitro model capable of predicting the in vivo permeability across the blood-brain barrier in the presence of glioblastoma. The selected in vitro method was a cell co-culture model of epithelial cell lines (MDCK and MDCK-MDR1) with a glioblastoma cell line (U87-MG). Several drugs were tested (letrozole, gemcitabine, methotrexate and ganciclovir). Comparison of the proposed in vitro model, MDCK and MDCK-MDR1 co-cultured with U87-MG, and in vivo studies showed a great predictability for each cell line, with R2 values of 0.8917 and 0.8296, respectively. Therefore, both cells lines (MDCK and MDCK-MDR1) are valid for predicting the access of drugs to the CNS in the presence of glioblastoma.

Role of Rituximab Addition to First-line Chemotherapy Regimens in Nodular Lymphocyte-predominant Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow-up of 8.4 years (interquartile range: 4.5-12.4) for treated patients, median overall survival (OS) was not reached and estimated 5-year OS was 97.8% and 5-year progression-free survival (PFS) was 84.5%. Five-year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%-3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss >10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2-0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II-III-IV NLPHL.

Radiolabeled Trastuzumab Solid Lipid Nanoparticles for Breast Cancer Cell: in Vitro and in Vivo Studies.

Radiolabeled trastuzumab (TRZ) loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and sonication techniques. The apoptosis mechanism of TRZ-SLNs was studied only with the MCF-7 cell line, while the cytotoxicity and cell binding capacity were investigated using breast cancer cells (MCF-7 and MDA-MB-231) and the human keratinocyte cell line (HaCaT). The particle sizes of TRZ-SLNs were found to be below 100 nm, and they possessed a negative charge. The high radiolabeling efficiency and good radiolabeling stability in saline and a cell culture medium were obtained in the results of radiolabeling studies. According to the in vitro studies, TRZ-SLNs were found to be biocompatible, and they effectively induced apoptosis in MCF-7 cells. After the parenteral injection of TRZ-SLNs into rats, a sustained release profile in blood circulation was achieved compared with free drug solution by the evaluation of pharmacokinetic parameters. As a conclusion, the study reveals that Technetium-99m (99mTc radiolabeled) TRZ loaded SLN formulations could be promising theranostic agents based on their characterization profiles, in vitro cellular uptake and apoptosis induction capacity, and in vivo pharmacokinetic profiles.

An Innovative Formulation Based on Nanostructured Lipid Carriers for Imatinib Delivery: Pre-Formulation, Cellular Uptake and Cytotoxicity Studies.

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification-sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and -32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer-Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

Lack of in-brace x-rays in compliant AIS patients wearing full-time TLSO braces associates with failure.

BACKGROUND: In-brace correction and brace compliance with thoraco-lumbo-sacral orthotic (TLSO) braces are associated with successful treatment of adolescent idiopathic scoliosis (AIS). This paper compares patients who had consistent radiographic documentation of in-brace correction to those who did not. METHODS: All skeletally immature (Risser 0-2) patients were treated for AIS (25-45°) with full-time TLSO braces that had compliance temperature monitors. All patients wore their braces at least 12 h a day. Brace failure was defined as curve progression to a surgical magnitude (≥ 50°). All patients were followed until brace discontinuation. RESULTS: Ninety patients (F 82, M 8) with an average age of 12.1 (10.1-15.0) years, Risser grade 0 (0-2), BMI percentile 48.5 (0.0-98.8), and daily brace wear of 16.5 (12.1-21.6) h/day were treated for 24.3 (8.0-66.6) months. Patients went through 1.7 (1-4) braces on average. Forty-two out of 90 (46.7%) patients had some amount of brace time with an unknown in-brace correction, which, on average, was 66.1% of their total treatment course (11.5-100). On univariate analysis, patients that did not have a repeat in-brace x-ray with major brace adjustments or new brace fabrication tended to be more skeletally immature (Risser 0 and tri-radiate open, p = 0.028), wear more braces throughout their treatment (2.0 vs 1.4, p < 0.001), were treated for a longer period of time (27 vs 22 months, p = 0.022), and failed bracing more often (47.6% vs 22.9%, p = 0.014). CONCLUSIONS: Patients who did not have new in-brace x-rays with major brace adjustments and/or new brace fabrication were 3.1 (95% CI 1.2-7.6) times more likely to fail bracing than patients who were re-checked with new in-brace x-rays. TRIAL REGISTRATION: ClinicalTrials.gov- NCT02412137 , initial registration date April 2015 LEVEL OF EVIDENCE: III.

Lactose-Gated Mesoporous Silica Particles for Intestinal Controlled Delivery of Essential Oil Components: An In Vitro and In Vivo Study.

Mesoporous silica microparticles functionalized with lactose for the specific release of essential oil components (EOCs) in the small intestine are presented. In vitro and in vivo intestinal models were applied to validate the microparticles (M41-EOC-L), in which the presence of lactase acts as the triggering stimulus for the controlled release of EOCs. Among the different microdevices prepared (containing thymol, eugenol and cinnamaldehyde), the one loaded with cinnamaldehyde showed the most significant Caco-2 cell viability reduction. On the other hand, interaction of the particles with enterocyte-like monolayers showed a reduction of EOCs permeability when protected into the designed microdevices. Then, a microdevice loaded with cinnamaldehyde was applied in the in vivo model of Wistar rat. The results showed a reduction in cinnamaldehyde plasma levels and an increase in its concentration in the lumen of the gastrointestinal tract (GIT). The absence of payload release in the stomach, the progressive release throughout the intestine and the prolonged stay of the payload in the GIT-lumen increased the bioavailability of the encapsulated compound at the site of the desired action. These innovative results, based on the specific intestinal controlled delivery, suggest that the M41-payload-L could be a potential hybrid microdevice for the protection and administration of bioactive molecules in the small intestine and colon.

Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer.

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2-C5). Tumour proliferation and hypoxic status were evaluated using 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)- and 18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

PURPOSE: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050). RESULTS: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

Differences in the clinical management of women and men after detection of a solitary pulmonary nodule in clinical practice.

OBJECTIVES: To explore differences in the clinical management of men and women in the 5 years after detecting a solitary pulmonary nodule (SPN) by chest radiograph or CT in routine clinical practice. METHODS: We followed up 545 men and 347 women with an SPN detected by chest radiograph or CT in a retrospective cohort of 25,422 individuals undergoing routine thoracic imaging in 2010-2011. We compared the frequency of each management strategy (no further test, immediate intervention or follow up) according to sex by means of chi-squared. We estimated the relative risk of women versus men of having been followed up instead of an immediate intervention using multivariate logistic regression. We compared by sex the time between detection of the nodule and lung cancer diagnosis, the time between diagnosis and death by means of Mann-Whitney U test and the cumulative effective dose of radiation in each management strategy by means of t test. RESULTS: Women were more likely than men to have follow-up rather than immediate intervention (aRR = 1.8, CI 1.3-2.7, p = 0.002), particularly in those who underwent CT (aRR = 4.2, CI 1.9-9.3, p < 0.001). The median time between SPN detection and lung cancer diagnosis was higher in women (4.2 months, interquartile range (IQR) 5.1) than in men (1.5 months, IQR 16.2). The mean cumulative effective dose was 21.3 mSv, 19.4 mSv in men and 23.9mv in women (p = 0.023). CONCLUSIONS: Our results could reflect decisions based on a greater suspicion of lung cancer in men. The incidental detection of SPNs is increasing, and it is necessary to establish clear strategies aimed to reduce variability in their management according to patient's sex. KEY POINTS: • After incidental finding of SPN, women were less likely to receive an immediate intervention. • Accumulative radiation was higher in women than in men. • Our results could reflect decisions based on a greater suspicion of lung cancer in men.

Contextualizing pertuzumab approval in the treatment of HER2-positive breast cancer patients.

The use of adjuvant pertuzumab in HER2-positive early-stage breast cancer has recently been approved by the EMA on the basis of data from the APHINITY trial. Accordingly, we have produced this opinion article with the aim of putting the study data in perspective against other add-on therapeutic strategies, to clarify methodological or statistical doubts about the study, and to define the population of high-risk patients with hormone receptor-negative breast cancer that we agree, in general, should be treated. With this approval, physicians must be well prepared to place the APHINITY study data in context. It is now up to each country to ratify the EMA-approved indications and to agree on reimbursement, and doctors must optimize their use based on knowledge and discussion with patients.

Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer.

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (≥20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients.

The determinants of lung cancer after detecting a solitary pulmonary nodule are different in men and women, for both chest radiograph and CT.

OBJECTIVES: To determine the factors associated with lung cancer diagnosis and mortality after detecting a solitary pulmonary nodule (SPN) in routine clinical practice, in men and in women for both chest radiograph and CT. MATERIALS AND METHODS: A 5-year follow-up of a retrospective cohort of of 25,422 (12,594 men, 12,827 women) patients aged ≥35 years referred for chest radiograph or CT in two hospitals in Spain (2010-2011). SPN were detected in 893 (546 men, 347 women) patients. We estimated the cumulative incidence of lung cancer at 5-years, the association of patient and nodule characteristics with SPN malignancy using Poisson logistic regression, stratifying by sex and type of imaging test. We calculated lung cancer specific mortality rate by sex and SPN detection and hazard rates by cox regression. RESULTS: 133 (14.9%) out of 893 patients with an SPN and 505 (2.06%) of the 24,529 patients without SPN were diagnosed with lung cancer. Median diameter of SPN in women who developed cancer was larger than in men. Men who had a chest radiograph were more likely to develop a lung cancer if the nodule was in the upper-lobes, which was not the case for women. In patients with an SPN, smoking increased the risk of lung cancer among men (chest radiograph: RR = 11.3, 95%CI 1.5-83.3; CT: RR = 7.5, 95%CI 2.2, 26.0) but smoking was not significantly associated with lung cancer diagnosis or mortality among women with an SPN. The relative risk of lung cancer diagnosis in women with SPN versus those without was much higher compared to men (13.7; 95%CI 9.2, 20.4 versus 6.2; 95%CI 4.9,7.9). CONCLUSION: The factors associated with SPN malignancy and 5-year lung cancer mortality were different among men and women, especially regarding smoking history and SPN characteristics, where we observed a relatively high rate of lung cancer diagnosis among female non-smokers.

Cumulative exposure to ionising radiation from diagnostic imaging tests: a 12-year follow-up population-based analysis in Spain.

OBJECTIVES: To calculate each patient's cumulative radiation exposure and the recurrent tests during a 12-year study period, according to sex and age, in routine practice. DESIGN: Retrospective cohort study. SETTING: A general hospital with a catchment population of 224 751 people, in the Southeast of Spain. PARTICIPANTS: Population belonged to the catchment area of that hospital in 2007. We collected all consecutive diagnostic imaging tests undergone by this population until 31 December 2018. We excluded: imaging tests that did not involve radiation exposure. MAIN OUTCOME MEASURES: The cumulative effective dose and the recurrent imaging tests by sex and age at entry of study. RESULTS: Of the 224 751 people, 154 520 (68.8%) underwent an imaging test. The population had 1 335 752 imaging tests during the period of study: 1 110 077 (83.0%) plain radiography; 156 848 (11.8%) CT; 63 157 (4.8%) fluoroscopy and 5670 (0.4%) interventional radiography. 25.4% of the patients who had a CT, underwent five or more CTs (5.4% in the 0-20 years age group). The median total cumulative effective dose was 2.10 mSv (maximum 3980.30) and 16.30 mSv (maximum 1419.30 mSv) if we considered only doses associated with CT. Women received more effective dose than men (median 2.38 vs median 1.90, p<0.001). A total of 7142 (4.6%) patients received more than 50 mSv, with differences in men and women (p<0.001) and 2.5% of the patients in the 0-20 years age group, if we considered only doses associated with CT. CONCLUSIONS: Nearly 5% of patients received doses higher than 50 mSv during the 12-year period of study and 2.5% of the patients in the 0-20 years age group, if we considered only doses associated with CT. The rate of recurrent examinations was high, especially in older patients, but also relevant in the 0-20 years age group.

Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study.

PURPOSE: GEICAM/2006-10 compared anastrozole (A) versus fulvestrant plus anastrozole (A + F) to test the hypothesis of whether a complete oestrogen blockade is superior to aromatase inhibitors alone in breast cancer patients receiving hormone adjuvant therapy. METHODS: Multicenter, open label, phase III study. HR+/HER2- EBC postmenopausal patients were randomized 1:1 to adjuvant A (5 years [year]) or A + F (A plus F 250 mg/4 weeks for 3 year followed by 2 year of A). Stratification factors: prior chemotherapy (yes/no); number of positive lymph nodes (0/1-3/≥ 4); HR status (both positive/one positive) and site. PRIMARY OBJECTIVE: disease-free survival (DFS). Planned sample size: 2852 patients. RESULTS: The study has an early stop due to the financer decision with 870 patients (437 randomized to A and 433 to A + F). Patient characteristics were well balanced. After a median follow-up of 6.24y and 111 DFS events (62 in A and 49 in A + F) the Hazard Ratio for DFS (combination vs. anastrozole) was 0.84 (95% CI 0.58-1.22; p = 0.352). The proportion of patients disease-free in arms A and A + F at 5 year and 7 year were 90.8% versus 91% and 83.6% versus 86.7%, respectively. Most relevant G2-4 toxicities (≥ 5% in either arm) with A versus A + F were joint pain (14.7%; 13.7%), fatigue (2.5%; 7.2%), bone pain (3%; 6.5%), hot flushes (3.5%; 5%) and muscle pain (2.8%; 5.1%). CONCLUSIONS: The GEICAM/2006-10 study did not show a statistically significant increase in DFS by adding adjuvant F to A, though no firm conclusions can be drawn because of the limited sample size due to the early stop of the trial. ClinicalTrials.gov: NCT00543127.