The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines ...with or without trastuzumab.
Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice.
Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis.
Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane.
Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.
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PLAG1 (pleomorphic adenoma gene 1) is frequently activated in Pleomorphic Adenoma (PA). Carcinoma ex-pleomorphic adenoma (CXPA) arises in PA and PLAG1 expression is believed to be maintained from PA ...to CXPA, as it can contribute to carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathological subtype of CXPA. Forty PA, 21 residual PA (without malignant transformation) and forty CXPA were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a two-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according histopathological subtype and invasiveness degree. Thirty seven PA (92.5%), fifteen residual PA (71%) and fourteen CXPA (35%) were positive for PLAG1. According CXPA group: intracapsular cases, Myoepithelial Carcinoma and Epithelial-Myoepithelial Carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathways activation and different clone cells. Additionally, PLAG1 expression seems to be present mainly in low grade carcinomas and in cases with early phase of invasion, due its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered as hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.
Background We showed previously that nasal mucociliary clearance was decreased in critically ill elderly subjects, most of whom had diabetes mellitus (DM) and/or hypertension (HTN). To determine if ...these changes were due to the effects of aging, disease, or critical illness, we studied nasal mucociliary clearance and mucus properties in an ambulatory population consisting of young, elderly, and healthy subjects and those with DM, HTN, or both. Methods Of 440 subjects contacted, 252 entered the study. The subjects were divided into the following groups: (1) healthy (n = 79, 18–94 years, 50 men) and (2) DM and/or HTN, of which 37 had DM (14–90 years, 12 men), 52 had HTN (23–90 years, 12 men), and 84 had both DM and HTN (25–82 years, 33 men). Subjects were also grouped by age: < 40 years, 40 to 59 years, and ≥ 60 years. We assessed demographic and clinical data, quality of life using the 36-Item Short Form Health Survey (SF-36) questionnaire, nasal mucociliary clearance using the saccharine transit test (STT), and in vitro mucus properties by examining the sneeze (high airflow) clearability and contact angle. A logistic regression analysis for prolonged STT > 12 min was used, and we controlled for age, sex, and diseases. Results Subjects aged > 60 years reported a decreased SF-36 physical component relative to other age groups. Sex, BMI, BP, heart rate, pulse oximetry, blood glucose level, and mucus properties were not associated with prolonged STT. Aging and DM and/or HTN independently increased the risk of prolonged STT. Conclusions Aging and DM, HTN, or both diseases are independently associated with decreased nasal mucociliary clearance. This may predispose toward respiratory infections.
Background Smoking is responsible for most COPD. Although people with COPD often have concomitant nasal disease, there are few studies that report physiologic or inflammatory changes in the upper ...airways in young asymptomatic smokers. We investigated physiologic and inflammatory changes in the nasal and lower airways of young smokers and if these changes were related to smoking history. Methods Seventy-two subjects aged between 18 and 35 years (32 healthy nonsmokers and 40 young smokers) participated in this study. We measured nasal mucociliary clearance (MCC), nasal mucus surface contact angle, cell counts, myeloperoxidase and cytokine concentrations in nasal lavage fluid, exhaled breath condensate (EBC) pH, and lung function. Results Smokers had faster MCC, an increased number of cells (macrophages, ciliated cells, and goblet cells), increased lavage myeloperoxidase concentration, and decreased EBC pH compared with nonsmokers. There was a significant inverse relationship between pack-year smoking history and EBC pH. There were no differences in lung function or mucus surface properties comparing smokers to nonsmokers. Conclusions Young adult smokers have functional and inflammatory changes in the nasal and lower airways and these correlate with smoking history. However, in these young smokers, smoking history was not associated with pulmonary function decline, probably because it is unlikely that spirometry detects early physiologic changes in the airways. Trial registry ClinicalTrials.gov ; No.: NCT01877291; URL: www.clinicaltrials.gov
Left atrial (LA) and left ventricular (LV) diastolic function analysis can yield new strategies to recognize early cardiac involvement and prognostic indicators in Chagas disease.
Patients with ...Chagas disease with the indeterminate (n = 69) or with the cardiac form (32 with changes limited to electrocardiography stage A, 25 with changes in LV systolic function but no heart failure HF; stage B, and 26 with HF) underwent evaluation of LV diastolic function (mitral inflow, pulmonary vein flow, color M-mode echocardiography, and tissue Doppler analysis), and LA function by three-dimensional echocardiography and strain analysis and were prospectively followed for the occurrence of clinical events. Echocardiograms were also obtained from 32 controls.
LV diastolic dysfunction was gradually more prevalent and severe across groups from patients with the indeterminate form of Chagas disease to patients with HF. Tissue Doppler was the best tool to demonstrate the worsening of LV diastolic function across the groups (E' velocity: controls, 12.6 ± 2.3 cm/sec; patients with the indeterminate form, 12.1 ± 3.1 cm/sec; stage A, 10.3 ± 2.9 cm/sec; stage B, 8.3 ± 2.8 cm/sec; patients with HF, 5.6 ± 1.9; P < .0001). Although maximum LA volume was increased only in patients with HF, minimum LA volume (controls, 8 ± 2 mL/m(2); patients with the indeterminate form, 8 ± 2 mL/m(2); stage A, 9 ± 3 mL/m(2); stage B, 11 ± 4 mL/m(2); patients with HF, 27 ± 17 mL/m(2); P < .0001) and precontraction LA volume (controls, 11 ± 3 mL/m(2); patients with the indeterminate form, 12 ± 3 mL/m(2); stage A, 13 ± 4 mL/m(2); stage B, 16 ± 5 mL/m(2); patients with HF, 32 ± 19 mL/m(2); P < .0001) were increased in all cardiac form groups. LA conductive function was depressed in all cardiac form groups, while LA contractile function was depressed only in patients with HF. Cox proportional-hazards regression analysis revealed that end-systolic LV diameter (hazard ratio, 1.6; 95% confidence interval, 0.9-2.8; P = .09), E' velocity (hazard ratio, 0.5; 95% confidence interval, 0.3-0.8; P = .001), and peak negative global LA strain (hazard ratio, 1.21; 95% confidence interval, 1.02-1.4; P = .03), were independent predictors of clinical events.
LV diastolic dysfunction was found in all forms of chronic Chagas disease, including those without LV systolic dysfunction. LV diastolic dysfunction may contribute to changes in LA volume and conductive function found in early stages of the cardiac form. Both LV diastolic function and LA contractile function were independent predictors of clinical events.
Background Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was ...to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy. Methods Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test–20. Results Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO. Conclusions In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification. Trial Registry ClinicalTrials.gov; No.: NCT02515786 ; URL: www.clinicaltrials.gov.
Summary Pulmonary involvement in leptospirosis has been increasingly reported in the last 20 years, being related to the severity and mortality of the disease. The pathogenesis of pulmonary ...hemorrhage in leptospirosis is not understood. Lung endothelial cells have been proposed as targets in the pathogenesis of lung involvement in leptospirosis through the activation of Toll-like receptor 2 or the complement system, which stimulates the release of cytokines that lead to the activation of adhesion molecules. The aim of this study was to investigate the involvement of immune pathways and of the intercellular and vascular cell adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule, respectively) in the lungs of patients with pulmonary involvement of leptospirosis. We studied the lungs of 18 patients who died of leptospirosis and compared them with 2 groups of controls: normal and noninfectious hemorrhagic lungs. Using immunohistochemistry and image analysis, we quantified the expression of the C3a anaphylatoxin receptor, intercellular adhesion molecule, vascular cell adhesion molecule, and Toll-like receptor 2 in small pulmonary vessels and in the alveolar septa. There was an increased expression of intercellular adhesion molecule ( P < .03) and C3a anaphylatoxin receptor ( P < .008) in alveolar septa in the leptospirosis group compared with the normal and hemorrhagic controls. In the vessels of the leptospirosis group, there was an increased expression of intercellular adhesion molecule ( P = .004), vascular cell adhesion molecule ( P = .030), and Toll-like receptor 2 ( P = .042) compared with the normal group. Vascular cell adhesion molecule expression in vessels was higher in the leptospirosis group compared with the hemorrhagic group ( P = .015). Our results indicate that immune receptors and adhesion molecules participate in the phenomena leading to pulmonary hemorrhage in leptospirosis.
Background Pigmented actinic keratosis (PAK) is a frequent simulator of lentigo maligna (LM) on the face upon clinical and dermoscopic examination, leading to misdiagnosis and unnecessary excisions. ...LM and PAK share dermoscopic features, making it difficult to have a confident diagnosis of PAK only with current dermoscopic knowledge. Objective We sought to evaluate sensitivity, specificity, and interobserver reproducibility of a novel dermoscopic feature, inner gray halo (IGH), and establish its histopathological and confocal correlations. Methods Dermoscopists blinded to histopathological diagnosis evaluated 58 PAK and 21 LM for the presence of IGH and dermoscopy parameters. Areas exhibiting IGH were marked and imaged with reflectance confocal microscopy before sampling for histopathologic correlation. Reflectance confocal microscopy and transverse histologic sectioning were performed in 14 of 79 cases. Results IGH was present in 53 of 58 (94.1%) PAK and in 5 of 21 (23.8%) LM in our series (sensitivity 91.4%; specificity 71.4%; positive predictive value 89.8%). Interobserver agreement was excellent (Kappa 0.846). Through transverse and perpendicular histologic sections, a dermoscopic-histologic-confocal correlation of IGH was established. Limitations A larger test set is needed to further validate the use of IGH in the differential diagnosis of PAK and facial pigmented lesions. Conclusion IGH is a novel dermoscopic parameter useful for the differentiation of PAK from LM on the face.
Summary Background A serogroup A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of ...its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA–TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. Methods We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA–TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1–29 years of a rural area roughly 13–15 and 2–4 months before and 4–6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Findings Roughly 1·8 million individuals aged 1–29 years received one dose of PsA–TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100 000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100 000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046–0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2–4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4–6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002–0·138; p<0·0001). Interpretation PSA–TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. Funding The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères.
A 27-year-old female patient was referred to our outpatient clinic with a 1-year history of shortness of breath when walking fast on level ground or when climbing stairs. Symptoms worsened after a ...second episode of spontaneous left pneumothorax, when a chest tube was placed in another hospital for complete lung expansion. During this hospitalization, an open lung biopsy was performed. There was no history of rhinorrhea, nasal congestion, cough, hemoptysis, wheezing, or expectoration.
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