RESUMEN
PURPOSE: We aimed to investigate controversial pediatric urolithiasis issues systematically, integrating expert consensus and comprehensive guidelines reviews. METHODS: Two semi-structured online focus group meetings were conducted to discuss the study's need and content, review current literature, and prepare the initial survey. Data were collected through surveys and focus group discussions. Existing guidelines were reviewed, and a second survey was conducted using the Delphi method to validate findings and facilitate consensus. The primary outcome measures investigated controversial issues, integrating expert consensus and guideline reviews. RESULTS: Experts from 15 countries participated, including 20 with 16+ years of experience, 2 with 11-15 years, and 4 with 6-10 years. The initial survey identified nine main themes, emphasizing the need for standardized diagnostic and treatment protocols and tailored treatments. Inter-rater reliability was high, with controversies in treatment approaches (score 4.6, 92% agreement), follow-up protocols (score 4.8, 100% agreement), and diagnostic criteria (score 4.6, 92% agreement). The second survey underscored the critical need for consensus on identification, diagnostic criteria (score 4.6, 92% agreement), and standardized follow-up protocols (score 4.8, 100% agreement). CONCLUSION: The importance of personalized treatment in pediatric urolithiasis is clear. Prioritizing low-radiation diagnostic tools, effectively managing residual stone fragments, and standardized follow-up protocols are crucial for improving patient outcomes. Integrating new technologies while ensuring safety and reliability is also essential. Harmonizing guidelines across regions can provide consistent and effective management. Future efforts should focus on collaborative research, specialized training, and the integration of new technologies in treatment protocols.
Asunto(s)
Guías de Práctica Clínica como Asunto , Urolitiasis , Humanos , Niño , Urolitiasis/terapia , Urolitiasis/diagnóstico , Consenso , Técnica DelphiRESUMEN
BACKGROUND: The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2- ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. METHODS: Postmenopausal patients with HR+/HER2- ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). RESULTS: At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. CONCLUSIONS: This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Fulvestrant , Neoplasias de la Mama/tratamiento farmacológico , Modelos de Riesgos Proporcionales , PosmenopausiaRESUMEN
Objectives: The aim of the present study was to conduct a review of the current literature evaluating the available evidence to date in terms of epidemiology, pathophysiology and clinical presentation of COVID-19 in relation to cardiovascular involvement, with a special focus on the myocarditis model, in the population of athletes (professional and recreational) who are preparing to return to competitions, with the ultimate aim of guaranteeing maximum safety for resuming sports activities. News: The COVID-19 pandemic has resulted in the inevitable cancellation of most sports activities, practiced at both a professional and amateur level, in order to minimize the risk of spreading the infection. Since the number of athletes who tested positive was rather high, the potential cardiac involvement in this peculiar population of subjects contracting the disease in a mild (asymptomatic, slightly symptomatic) or moderate form, has recently raised concerns following the observation of cases of recorded myocardial damage, myocarditis, arrhythmias and a first reported case of Sudden Cardiac Death (SCD) in a 27-year-old professional basketball player. Several studies even seem to confirm the possibility of permanent impairment of the cardiorespiratory system following the infection. Medical history, biomarkers, electrocardiographical and cardiac imaging features appear to be crucial in distinguishing cardiovascular alterations related to COVID-19 infection from typical adaptations to exercise related to athletes' heart. Prospects and Projects: Clarifications and prospective data based on long-term follow-ups on larger populations of athletes are still needed to exclude the development of myocardial damage capable of negatively affecting prognosis and increasing cardiovascular risk in athletes recovered from COVID-19 in asymptomatic (simple positivity to SARS-COV-2) or in a mild form. Conclusion: From a clinical point of view extreme caution is necessary when planning the return to sport (Return To Play-RTP) of athletes recovered from a mild or asymptomatic form of COVID-19: a careful preliminary medical-sports evaluation should be carried out in order to assess the potential development of myocardial damage that would increase their cardiovascular risk.
Objectifs: Le but cette étude était de mener une revue de la littérature actuelle évaluant les différents éléments disponibles en termes d'épidémiologie, de physiopathologie et de présentation clinique de l'atteinte cardio-vasculaire du COVID-19. Une attention particulière sera donnée aux lésions myocardiques dans la population des athlètes, à la fois de niveau professionnel et amateur, qui s'apprêtent à reprendre la compétition, dans le but de garantir une sécurité maximale dans la reprise des activités sportives. Actualités: La pandémie de COVID-19 a entraîné l'annulation inévitable de la plupart des activités sportives, pratiquées à la fois à un niveau professionnel et amateur, afin de minimiser le risque de propagation de l'infection. Le nombre d'athlètes testés positifs étant plutôt élevé, les répercussions cardiaques potentielles dans cette population particulière de sujets contractant la maladie sous une forme légère (asymptomatique, légèrement symptomatique) ou modérée, a récemment soulevé des inquiétudes suite à l'observation de cas de lésions myocardiques, de myocardites, d'arythmies et d'un premier cas signalé de mort subite chez un basketteur professionnel de 27 ans. De plus, plusieurs études semblent confirmer la possibilité d'une altération permanente du système cardiorespiratoire suite à l'infection. Les antécédents médicaux, les biomarqueurs, les caractéristiques électrocardiographiques et à l'imagerie cardiaque semblent ainsi être des éléments cruciaux pour pouvoir distinguer les altérations cardiovasculaires liées à l'infection au COVID-19 des adaptations typiques à l'exercice des cÅurs d'athlètes. Perspectives et projets: Des précisions et des données prospectives basées sur des suivis à long terme sur des populations plus importantes d'athlètes sont encore nécessaires pour exclure le développement de lésions myocardiques capables d'affecter négativement le pronostic et d'augmenter le risque cardiovasculaire chez les athlètes en rémission d'une infection au COVID-19 asymptomatique (positivité simple au SARS-COV-2) ou sous une forme légère. Conclusion: D'un point de vue clinique, une extrême prudence est nécessaire lors de la planification du retour au sport des athlètes en rémission d'une forme légère ou asymptomatique de COVID-19: une évaluation médico-sportive minutieuse de ces patients doit être effectuée afin d'évaluer le développement potentiel de lésions myocardiques qui augmenteraient leur risque cardiovasculaire.
RESUMEN
BACKGROUND: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months). PATIENTS AND METHODS: This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2- ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). RESULTS: Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (â¼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug-drug interaction between ribociclib and fulvestrant or new safety signals were observed. CONCLUSIONS: This analysis reported extended OS follow-up in MONALEESA-3. mOS was â¼12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.
Asunto(s)
Neoplasias de la Mama , Adolescente , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Método Doble Ciego , Femenino , Fulvestrant , Humanos , Posmenopausia , Purinas , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de ProgesteronaRESUMEN
BACKGROUND: The American Society of Anaesthesiologists' Physical Status Score (ASA) is a key variable in predictor models of surgical outcome and "appropriate use criteria". However, at the time when such tools are being used in decision-making, the ASA rating is typically unknown. We evaluated whether the ASA class could be predicted statistically from Charlson Comorbidy Index (CCI) scores and simple demographic variables. METHODS: Using established algorithms, the CCI was calculated from the ICD-10 comorbidity codes of 11'523 spine surgery patients (62.3 ± 14.6y) who also had anaesthetist-assigned ASA scores. These were randomly split into training (N = 8078) and test (N = 3445) samples. A logistic regression model was built based on the training sample and used to predict ASA scores for the test sample and for temporal (N = 341) and external validation (N = 171) samples. RESULTS: In a simple model with just CCI predicting ASA, receiver operating characteristics (ROC) analysis revealed a cut-off of CCI ≥ 1 discriminated best between being ASA ≥ 3 versus < 3 (area under the curve (AUC), 0.70 ± 0.01, 95%CI,0.82-0.84). Multiple logistic regression analyses including age, sex, smoking, and BMI in addition to CCI gave better predictions of ASA (Nagelkerke's pseudo-R2 for predicting ASA class 1 to 4, 46.6%; for predicting ASA ≥ 3 vs. < 3, 37.5%). AUCs for discriminating ASA ≥ 3 versus < 3 from multiple logistic regression were 0.83 ± 0.01 (95%CI, 0.82-0.84) for the training sample and 0.82 ± 0.01 (95%CI, 0.81-0.84), 0.85 ± 0.02 (95%CI, 0.80-0.89), and 0.77 ± 0.04 (95%CI,0.69-0.84) for the test, temporal and external validation samples, respectively. Calibration was adequate in all validation samples. CONCLUSIONS: It was possible to predict ASA from CCI. In a simple model, CCI ≥ 1 best distinguished between ASA ≥ 3 and < 3. For a more precise prediction, regression algorithms were created based on CCI and simple demographic variables obtainable from patient interview. The availability of such algorithms may widen the utility of decision aids that rely on the ASA, where the latter is not readily available.
Asunto(s)
Enfermedades de la Columna Vertebral , Área Bajo la Curva , Comorbilidad , Humanos , Complicaciones Posoperatorias/epidemiología , Curva ROC , Estudios Retrospectivos , Enfermedades de la Columna Vertebral/cirugíaRESUMEN
BACKGROUND: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. PATIENTS AND METHODS: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. RESULTS: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042). CONCLUSIONS: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT NUMBER: 2013-002662-40. CLINICALTRIALS.GOV IDENTIFIER: NCT02411344.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Letrozol/administración & dosificación , Persona de Mediana Edad , Terapia Neoadyuvante , Invasividad Neoplásica , Pronóstico , Inducción de Remisión , Trastuzumab/administración & dosificaciónRESUMEN
An innovative, non-ionizing technique to diagnose osteoporosis on lumbar spine and femoral neck was evaluated through a multicenter study involving 1914 women. The proposed method showed significant agreement with reference gold standard method and, therefore, a potential for early osteoporosis diagnoses and possibly improved patient management. INTRODUCTION: To assess precision (i.e., short term intra-operator precision) and diagnostic accuracy of an innovative non-ionizing technique, REMS (Radiofrequency Echographic Multi Spectrometry), in comparison with the clinical gold standard reference DXA (dual X-ray absorptiometry), through an observational multicenter clinical study. METHODS: In a multicenter cross-sectional observational study, a total of 1914 postmenopausal women (51-70 years) underwent spinal (n = 1553) and/or femoral (n = 1637) DXA, according to their medical prescription, and echographic scan of the same anatomical sites performed with the REMS approach. All the medical reports (DXA and REMS) were carefully checked to identify possible errors that could have caused inaccurate measurements: erroneous REMS reports were excluded, whereas erroneous DXA reports were re-analyzed where possible and otherwise excluded before assessing REMS accuracy. REMS precision was independently assessed. RESULTS: In the spinal group, quality assessment on medical reports produced the exclusion of 280 patients because of REMS errors and 78 patients because of DXA errors, whereas 296 DXA reports were re-analyzed and corrected. Analogously, in the femoral group there were 205 exclusions for REMS errors, 59 exclusions for DXA errors, and 217 re-analyzed DXA reports. In the resulting dataset (n = 1195 for spine, n = 1373 for femur) REMS outcome showed a good agreement with DXA: the average difference in bone mineral density (BMD, bias ± 2SD) was -0.004 ± 0.088 g/cm2 for spine and - 0.006 ± 0.076 g/cm2 for femur. Linear regression showed also that the two methods were well correlated: standard error of the estimate (SEE) was 5.3% for spine and 5.8% for femur. REMS precision, expressed as RMS-CV, was 0.38% for spine and 0.32% for femur. CONCLUSIONS: The REMS approach can be used for non-ionizing osteoporosis diagnosis directly on lumbar spine and femoral neck with a good level of accuracy and precision. However, a more rigorous operator training is needed to limit the erroneous acquisitions and to ensure the full clinical practicability.
Asunto(s)
Cuello Femoral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Osteoporosis Posmenopáusica/diagnóstico por imagen , Absorciometría de Fotón/métodos , Anciano , Densidad Ósea/fisiología , Estudios Transversales , Femenino , Cuello Femoral/fisiopatología , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Reproducibilidad de los Resultados , Ultrasonografía/métodosRESUMEN
PURPOSE: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. METHODS: This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥ 50 and older in different areas of Italy in the period 2012-2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. RESULTS: The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. CONCLUSIONS: Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.
Asunto(s)
Osteoporosis Posmenopáusica/diagnóstico , Osteoporosis Posmenopáusica/epidemiología , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/epidemiología , Posmenopausia , Anciano , Densidad Ósea , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Fracturas Osteoporóticas/etiología , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
We report on the direct experimental observation of the 7pP23/2â7dD2 optical transitions in 209 and 210 francium isotopes. By continuously monitoring the fluorescence emitted by the isotopes collected in a magneto-optical trap (MOT), the electric dipole transitions 7pP23/2â7dD25/2 of Fr209, not yet experimentally observed, and 7pP23/2â7dD25/2, 7pP23/2â7dD25/2 of Fr210 were detected as sub-Doppler depletion dips of the cold atom population. This approach allowed unambiguous identification of the excited state hyperfine structures, even in the absence of a large stable vapor. Our findings demonstrate the effectiveness and the flexibility of fluorescence monitoring of trap depletion upon laser excitation, and broaden the experimental knowledge of francium isotopes and their electronic and nuclear properties. These results will have a relevant impact on ongoing researches for low-energy testing of fundamental symmetries with francium, from atomic parity non-conservation to the electron dipole moment.
RESUMEN
The study aimed to assess in a population of subjects with rheumatoid arthritis (RA) treated with methotrexate (MTX) how the initial approach to the treatment influenced subsequent disability. We performed a cross-sectional analysis of data collected during the baseline visit of the MARI study, a multicenter observational study on patients with RA on treatment with MTX for at least 12 months. Subjects who fulfilled the Health Assessment Questionnaire (HAQ) were included in the evaluation. For every patient we retrospectively evaluated the disease duration, the duration of symptoms before the diagnosis, the time elapsed before first MTX treatment, the initial MTX dose, and the concomitant medications in the first six months of therapy. Disability was defined as a DI-HAQ score ≥1. The study population included 1015 subjects. Patients with a DI-HAQ score ≥1 had a longer duration of symptoms before diagnosis, a higher delay in treatment initiation, a lower initial dose of MTX and a more frequent co-treatment with symptomatic drugs. Disability was found less frequently in subjects treated with other concomitant disease modifying anti-rheumatic drugs (DMARDs) but not with biological agents. Logistic regression analysis identified as significant predictors of disability: older age, female sex, a longer time to complete diagnosis, a delay in starting MTX treatment higher than 6 months, and a concomitant treatment with symptomatic drugs, while a combination therapy with other DMARDs was associated with a lower risk of disability. A late diagnosis and a delay in starting a treatment with MTX are associated with poorer functional outcomes in patients with RA.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Adulto , Anciano , Estudios Transversales , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To investigate in the NeoSphere trial the contribution of the immune system to pathologic complete response in the breast (pCRB) after neoadjuvant docetaxel with trastuzumab (TH), pertuzumab (TP), or both (THP), or monoclonal antibodies alone (HP). PATIENTS AND METHODS: Immune gene mRNA expression (n = 350, 83.8%), lymphocyte infiltration (TIL, n = 243, 58.3%), and PDL1 by immunohistochemistry (n = 305, 73.1%) were correlated with pCRB. We studied five selected genes (IFNG, PD1, PDL1, PDL2, CTLA4) and six immune metagenes corresponding to plasma cells (IGG), T cells (CD8A), antigen-presenting cells (MHC2), and to MHC1 genes (MHC1), STAT1 co-expressed genes (STAT1), and interferon-inducible genes (IF-I). Gene expression data from the NOAH trial were used for validation. RESULTS: TIL as continuous variable and PDL1 protein expression were not significantly associated with pCRB. Expression of immune genes/metagenes had different association with pCRB after THP than after other therapies. With THP, higher expression of PD1 and STAT1, or any among PDL1, CTLA4, MHC1, and IF-I were linked with lower pCRB. In the combined TH/TP/HP treatment group, in multivariate analysis, higher expression of PD1, MHC2, and STAT1 were linked with pCRB, and higher PDL1, MHC1, or IF-I to lower pCRB. In the NOAH, a similar association of higher STAT1 with higher pCRB, and higher MHC1 and IF-I with lower pCRB was found for trastuzumab/chemotherapy but not for chemotherapy treatment only. CONCLUSIONS: The immune system modulates response to therapies containing trastuzumab and pertuzumab. Greatest benefit from THP is observed for low expression of some immune markers (i.e. MHC1, CTLA4). The involvement of PDL1 in resistance supports testing combinations of HER2-directed antibodies and immune-checkpoint inhibitors.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Terapia Neoadyuvante/métodos , Receptor ErbB-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Femenino , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Persona de Mediana Edad , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Methotrexate (MTX) is the first choice in the treatment of rheumatoid arthritis (RA), but the doses and regimens vary significantly. For this purpose, we conducted an observational study on the use of MTX for RA in Italy (MARI study). METHODS: The MARI study included 1,327 RA patients on MTX treatment for at least 12 months, at 60 Italian rheumatology units. Concomitant medications with corticosteroids, other DMARDs or biological therapies were recorded. The clinical assessment included the Disease Activity Score 28 (DAS28) and the serological positivity for the rheumatoid factor or for the anti-citrullinated protein antibodies. RESULTS: The included patients were treated with either oral (n=288) or parenteral (n=1039) MTX. Only 15.5% of the total number of the patients was on adequate MTX dose (i.e. ≥ 15 mg for the oral route of administration and >12 mg for the parenteral one). The initially established MTX dose was modified in 37.1% of the patients, for intolerance or clinical criteria. A DAS28 remission (DAS28 <2.6) was observed only in 58.5% of the cases, while 52.9% of the patients still presenting an active form of the disease were on suboptimal doses of MTX. CONCLUSIONS: The weekly dose of MTX prescribed for the treatment of RA is often suboptimal, even in conditions of inadequate control of the disease activity. The recommendations for the use of MTX in RA patients should take into account the efficacy and tolerability data derived from its use in real clinical practice.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Glucocorticoides , Metotrexato , Anciano , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/fisiopatología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Italia/epidemiología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Gravedad del Paciente , Inducción de Remisión/métodos , Factor Reumatoide/sangre , Resultado del TratamientoRESUMEN
Psoriatic arthritis is an inflammatory seronegative spondyloarthropathy that occurs in approximately 25% of patients with psoriasis and is a progressive and severely disabling disease. Most patients have had psoriasis for several years before the development of arthritis or develop the joint and skin condition simultaneously. Given the absence of specific diagnostic test for psoriatic arthritis, clinical findings remain the standard criteria for the diagnosis. Patients with psoriasis presenting to the dermatologist for management of their skin disease may have joint symptoms related or not to psoriatic arthritis and similarly arthritic patients presenting to a rheumatologist for the management of psoriatic arthritis may have skin lesions related or not to psoriasis. In this paper an expert panel of specialist belonging to the Associazione Dermatologi Ospedalieri Italiani (ADOI) and Collegio dei Reumatologi Ospedalieri Italiani (CROI) analysed the international literature and scientific recommendations and also investigated the Italian setting. It has been demonstrated in the literature that a multidisciplinary clinical setting may benefit patients with psoriatic arthritis from both diagnostic and therapeutic points of view. The comparative analysis of the Italian clinical records used by ADOI and CROI have highlighted some substantial differences. Collaboration between the dermatologist and rheumatologist allows for a more complete appreciation of the overall skin and musculoskeletal disease burden, and subsequently leads to a more comprehensive treatment approach.
Asunto(s)
Artritis Psoriásica/terapia , Dermatología , Pautas de la Práctica en Medicina , Reumatología , HumanosRESUMEN
Osteoarthritis (OA) is the most common painful arthritic disease in adults, causes severe disability and worsens the quality of life of the patients. The aim of this survey, carried out on 147 Italian orthopedic doctors who attended an ISIAT (International Symposium Intra Articular Treatment) educational course in Barcelona, was to investigate some aspects of daily clinical practice in the management of OA: the most used pharmacological treatments, compliance to the most important Guidelines, the advantages of COXIBs in this setting and pharmacoeconomic aspects. The main results of this survey are: a) inflammation has become the main target in OA; b) Guidelines are a useful and valid tool for daily clinical practice; c) acetaminophen is no longer a valid therapeutical option for OA patients; d) anti-inflammatory drugs (NSAIDs and COXIBs) have a primary role in the management of OA, due to their dual activity (anti-inflammatory and analgesic); e) selectivity of COXIBs for COX-2 is very important; f) within the COXIB class, the therapeutic value of etoricoxib has been widely recognized, especially in terms of safety and cost/benefit ratio.
Asunto(s)
Antiinflamatorios/uso terapéutico , Utilización de Medicamentos , Osteoartritis/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Humanos , Italia , FarmacogenéticaRESUMEN
As a result of population ageing worldwide, osteoporotic fractures are becoming a serious problem in the western world. Osteoporotic fractures are associated with a significant burden in terms of morbidity, mortality, and economic costs. Although less frequent than in women, male osteoporosis is also a relatively common problem. Since bone loss and fragility fractures in men have been recognized as a serious medical condition, over the last two decades several studies have investigated a number of aspects related to the pathogenesis, diagnosis and assessment, prevention and treatment of male osteoporosis. A better understanding of factors underlying increased bone fragility in men has led to the definition of appropriate screening and diagnostic strategies, and the development of treatments that have shown to improve bone mineral density and, in some cases, reduce fracture risk in men as well as in women. This review will summarize recent findings on male osteoporosis with a particular focus on risk factors and causes of bone loss, and available therapeutic options.
Asunto(s)
Osteoporosis , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Osteoporosis/terapia , Fracturas Osteoporóticas/etiología , Factores SexualesRESUMEN
BACKGROUND: Studies have investigated the effects of training under hypoxia (HYP) after several weeks in a male population. However, there is still a lack of knowledge on the acute hypoxic effects on physiology and muscle recovery in a female population. METHODS: This randomized-controlled trial aimed to investigate the acute effects of muscle damaging exercise, performed in HYP and normoxia (CON), on physiological responses and recovery characteristics in healthy females. Key inclusion criteria were recreationally active female participants between the age of 18 to 35 years without any previous surgeries and injuries, whilst key exclusion criteria were acute pain situations, pregnancy, and medication intake. The females conducted a muscle-damaging protocol, comprising 5 × 20 drop-jumps, in either HYP (FiO2: 12%) or CON (FiO2: 21%). Physiological responses, including capillary oxygenation (SpO2), muscle oxygenation (SmO2), heart rate (HR), core- (Tcore) and skin- (Tskin) temperature were assessed at the end of each exercise set. Recovery characteristics were quantified by taking venous blood samples (serum creatine-kinase [CK], C-reactive protein [CRP] and blood sedimentation rate [BSR]), assessing muscle swelling of the quadriceps femoris muscle, maximum voluntary isometric contraction (MVIC) of the knee extensor muscles, countermovement jump (CMJ) performance and muscle soreness ratings (DOMS) at 24-, 48- and 72-hrs post-exercise. RESULTS: SpO2 (HYP: 76.7 ± 3.8%, CON: 95.5 ± 1.7%, p < 0.001) and SmO2 (HYP: 60.0 ± 9.3, CON: 73.4 ± 5.8%, p = 0.03) values were lower (p < 0.05) in HYP compared to CON at the end of the exercise-protocol. No physiological differences between HYP and CON were observed for HR, Tcore, and Tskin (all p > 0.05). There were also no differences detected for any recovery variable (CK, CRP, BSR, MVIC, CMJ, and DOMS) during the 72-hrs follow-up period between HYP and CON (all p > 0.05). CONCLUSION: In conclusion, our results showed that muscle damaging exercise under HYP leads to reduced capillary and muscle oxygenation levels compared to normoxia with no difference in inflammatory response and muscle recovery during 72 h post-exercise. TRIAL REGISTRATION: NCT04902924, May 26th 2021.
RESUMEN
Resonant excited state absorption (ESA) and relaxation processes in Tb(3+)-doped aluminosilicate glasses are quantitatively evaluated. A model describing the excitation steps and upconversion emission is developed and applied to interpret the results from laser-induced surface deformation using thermal mirror spectroscopy. The fluorescence quantum efficiency of level (5)D(4) was found to be close to unity and concentration independent while, for the level (5)D(3), it decreases with Tb(3+) concentration. Emission spectroscopy measurements supported these results. ESA cross sections are found to be more than three orders of magnitude higher than the ground state absorption cross section.