RESUMEN
BACKGROUND: The association between obesity and prognosis in HER2-positive early breast cancer remains unclear, with limited data available. This study aimed to determine the impact of body mass index (BMI) at baseline and weight change after 2 years on outcomes of patients with HER2-positive early breast cancer. METHODS: ALTTO was a randomized phase III trial in patients with HER2-positive early breast cancer. BMI was collected at randomization and 2 years after. WHO BMI categories were used: underweight, <18.5 kg/m2; normal weight, 18.5 to <25 kg/m2; overweight, ≥25 to <30 kg/m2; and obese ≥30 kg/m2. A weight change from baseline of ≥5.0% and ≤5.0% was categorized as weight gain and weight loss. The impact of BMI at randomization and of weight change on disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were investigated with multivariate analyses, adjusting for baseline patients and tumor characteristics. RESULTS: A total of 8,381 patients were included: 187 (2.2%), 3,797 (45.3%), 2,690 (32.1%), and 1,707 (20.4%) were underweight, normal weight, overweight, and obese at baseline, respectively. Compared with normal weight, being obese at randomization was associated with a significantly worse DDFS (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.04-1.50) and OS (aHR, 1.27; 95% CI, 1.01-1.60), but no significant difference in DFS (aHR, 1.14; 95% CI, 0.97-1.32). Weight loss ≥5.0% at 2 years after randomization was associated with significantly poorer DFS (aHR, 1.34; 95% CI, 1.05-1.71), DDFS (aHR, 1.46; 95% CI, 1.07-1.98), and OS (aHR, 1.83; 95% CI, 1.18-2.84). Hormone receptor and menopausal status but not anti-HER2 treatment type influenced outcomes. Toxicities were more frequent in obese patients. CONCLUSIONS: In patients with HER2-positive early breast cancer, obesity at baseline is a poor prognostic factor. Weight loss during treatment and follow-up negatively impacts clinical outcomes. Dietary counseling should be part of survivorship care programs.
Asunto(s)
Índice de Masa Corporal , Neoplasias de la Mama , Obesidad/complicaciones , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Sobrepeso/complicaciones , Pronóstico , Receptor ErbB-2 , Tasa de SupervivenciaRESUMEN
With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug-drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITDmut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease.
Asunto(s)
Antifúngicos/uso terapéutico , Quimioprevención/tendencias , Infecciones Fúngicas Invasoras/prevención & control , Leucemia Mieloide Aguda/tratamiento farmacológico , Estaurosporina/análogos & derivados , Triazoles/uso terapéutico , Antifúngicos/clasificación , Quimioprevención/métodos , Interacciones Farmacológicas , Drogas en Investigación/uso terapéutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/microbiología , Leucemia Mieloide Aguda/mortalidad , Pronóstico , Estaurosporina/uso terapéuticoRESUMEN
The coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.
Asunto(s)
Defensa Civil/organización & administración , Infecciones por Coronavirus/epidemiología , Coronavirus , Brotes de Enfermedades , Manejo de Atención al Paciente , Neumonía Viral/epidemiología , Adulto , Betacoronavirus , COVID-19 , Alemania/epidemiología , Humanos , Persona de Mediana Edad , Pandemias , Medición de Riesgo , SARS-CoV-2 , Centros de Atención Terciaria , TriajeRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) and some of their nitrated derivatives, NPAHs, are seemingly ubiquitous in the atmospheric environment. Atmospheric lifetimes may nevertheless vary within a wide range, and be as short as a few hours. The sources and sinks of NPAH in the atmosphere are not well understood. With a Lagrangian field experiment and modeling, we studied the conversion of the semivolatile PAHs fluoranthene and pyrene into the 2-nitro derivatives 2-nitrofluoranthene and 2-nitropyrene in a cloud-free marine atmosphere on the time scale of hours to 1 day between a coastal and an island site. Chemistry and transport during several episodes was simulated by a Lagrangian box model i.e., a box model coupled to a Lagrangian particle dispersion model, FLEXPART-WRF. It is found that the chemical kinetic data do capture photochemical degradation of the 4-ring PAHs under ambient conditions on the time scale of hours to 1 day, while the production of the corresponding NPAH, which sustained 2-nitrofluoranthene/fluoranthene and 2-nitropyrene/pyrene yields of (3.7 ± 0.2) and (1.5 ± 0.1)%, respectively, is by far underestimated. Predicted levels of NPAH come close to observed ones, when kinetic data describing the reactivity of the OH-adduct were explored by means of theoretically based estimates. Predictions are also underestimated by 1-2 orders of magnitude, when NPAH/PAH yields reported from laboratory experiments conducted under high NOx conditions are adopted for the simulations. It is concluded that NPAH sources effective under low NOx conditions, are largely underestimated.
Asunto(s)
Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Atmósfera , Monitoreo del Ambiente , Nitratos , Óxidos de NitrógenoRESUMEN
Despite promising results with targeted drugs, chemoimmunotherapy with fludarabine, cyclophosphamide (FC), and rituximab (R) remains the standard therapy for fit patients with untreated chronic lymphocytic leukemia (CLL). Herein, we present the long-term follow-up of the randomized CLL8 trial reporting safety and efficacy of FC and FCR treatment of 817 treatment-naïve patients with CLL. The primary end point was progression-free survival (PFS). With a median follow-up of 5.9 years, median PFS were 56.8 and 32.9 months for the FCR and FC group (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.50-0.69, P < .001). Median overall survival (OS) was not reached for the FCR group and was 86.0 months for the FC group (HR, 0.68; 95% CI, 0.54-0.89, P = .001). In patients with mutated IGHV (IGHV MUT), FCR improved PFS and OS compared with FC (PFS: HR, 0.47; 95% CI, 0.33-0.68, P < .001; OS: HR, 0.62; 95% CI, 0.34-1.11, P = .1). This improvement remained applicable for all cytogenetic subgroups other than del(17p). Long-term safety analyses showed that FCR had a higher rate of prolonged neutropenia during the first year after treatment (16.6% vs 8.8%; P = .007). Secondary malignancies including Richter's transformation occurred in 13.1% in the FCR group and in 17.4% in the FC group (P = .1). First-line chemoimmunotherapy with FCR induces long-term remissions and highly relevant improvement in OS in specific genetic subgroups of fit patients with CLL, in particular those with IGHV MUT. This trial was registered at www.clinicaltrials.gov as #NCT00281918.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/terapia , Rituximab/administración & dosificación , Vidarabina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/epidemiología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Rituximab/efectos adversos , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversosRESUMEN
BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. METHODS: Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33-81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage. Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days or to intravenous bendamustine (90 mg/m(2) per day) for the first 2 days of each cycle. Rituximab 375 mg/m(2) was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m(2) during the next five cycles on day 1. The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5% or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio (HR) based on the 90·4% CI. The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included in the intention-to-treat population: 282 patients in the fludarabine, cyclophosphamide, and rituximab group and 279 in the bendamustine and rituximab group. After a median observation time of 37·1 months (IQR 31·0-45·5) median progression-free survival was 41·7 months (95% CI 34·9-45·3) with bendamustine and rituximab and 55·2 months (95% CI not evaluable) with fludarabine, cyclophosphamide, and rituximab (HR 1·643, 90·4% CI 1·308-2·064). As the upper limit of the 90·4% CI was greater than 1·388 the null hypothesis for the corresponding non-inferiority hypothesis was not rejected. Severe neutropenia and infections were more frequently observed with fludarabine, cyclophosphamide, and rituximab (235 [84%] of 279 vs 164 [59%] of 278, and 109 [39%] vs 69 [25%], respectively) during the study. The increased frequency of infectious complications with fludarabine, cyclophosphamide, and rituximab was more pronounced in patients older than 65 years. INTERPRETATION: The combination of fludarabine, cyclophosphamide, and rituximab remains the standard front-line therapy in fit patients with chronic lymphocytic leukaemia, but bendamustine and rituximab is associated with less toxic effects. FUNDING: Roche Pharma AG, Mundipharma, German Federal Ministry of Education and Research.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Clorhidrato de Bendamustina/administración & dosificación , Ciclofosfamida/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Rituximab/administración & dosificación , Tasa de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
This study investigated the effects of a high-intensity cycling exercise on changes in spectral and temporal aspects of electroencephalography (EEG) measured from 10 experienced cyclists. Cyclists performed a maximum aerobic power test on the first testing day followed by a time-to-exhaustion trial at 85% of their maximum power output on 2 subsequent days that were separated by â¼48 h. EEG was recorded using a 64-channel system at 500 Hz. Independent component (IC) analysis parsed the EEG scalp data into maximal ICs. An equivalent current dipole model was calculated for each IC, and results were clustered across subjects. A time-frequency analysis of the identified electrocortical clusters was performed to investigate the magnitude and timing of event-related spectral perturbations. Significant changes (P < 0.05) in electrocortical activity were found in frontal, supplementary motor and parietal areas of the cortex. Overall, there was a significant increase in EEG power as fatigue developed throughout the exercise. The strongest increase was found in the frontal area of the cortex. The timing of event-related desynchronization within the supplementary motor area corresponds with the onset of force production and the transition from flexion to extension in the pedaling cycle. The results indicate an involvement of the cerebral cortex during the pedaling task that most likely involves executive control function, as well as motor planning and execution.
Asunto(s)
Ciclismo/fisiología , Corteza Cerebral/fisiología , Ejercicio Físico , Adolescente , Adulto , Electroencefalografía , Lóbulo Frontal/fisiología , Humanos , Masculino , Corteza Motora/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Lóbulo Parietal/fisiología , Procesamiento de Señales Asistido por Computador , Adulto JovenRESUMEN
PURPOSE: A phase I/II trial to assess safety and efficacy of the combination bendamustine, rituximab, and lenalidomide (BRL) in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Seventeen relapsed or refractory (R/R) and five previously untreated (FL) CLL patients were enrolled in the trial. In the R/R cohort, four different dose levels of lenalidomide (maximum 15 mg/d) were used. In the FL cohort, lenalidomide was dose escalated from 5 mg/d to 15 mg/d. Bendamustine was used at doses of 50 or 90 mg/m(2) for R/R or FL treatment, respectively. 375 mg/m(2) Rituximab were used for the first and 500 mg/m(2) for subsequent treatment courses. Treatment consisted of up to six courses of 28 d. RESULTS: The maximal tolerable dose of lenalidomide was 5 mg/d. The response rate was 47.1% in R/R and 60% in FL patients. Median progression-free survival was 8.0 months. Median overall survival was 22.9 and 12.3 months, respectively, in R/R and FL patients. Grade 3/4 hematological toxicity was observed in 71.4%, and severe infections in 47.6% of patients. Due to high toxicity and low response rate of BRL, the trial was closed prematurely. CONCLUSION: BRL was associated with a high toxicity rate, a high number of treatment interruptions, and a low remission rate. Therefore, BRL cannot be considered an appropriate treatment option for patients with CLL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/administración & dosificación , Aberraciones Cromosómicas , Esquema de Medicación , Femenino , Humanos , Lenalidomida , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Pronóstico , Rituximab/administración & dosificación , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Resultado del TratamientoAsunto(s)
Leucemia Linfocítica Crónica de Células B/complicaciones , Neoplasias Primarias Secundarias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Femenino , Humanos , Incidencia , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Endovascular adjuncts, like atherectomy, were developed to improve outcomes of endovascular arterial interventions. The true impact of atherectomy on endovascular outcomes remains to be determined, and little data exist on the influence of atherectomy on tibial interventions. Our study compares early and late outcomes of tibial intervention with angioplasty vs atherectomy-assisted interventions. METHODS: We completed a retrospective review of all tibial interventions between 2008 and 2010. Outcomes were analyzed using single and multivariate analysis, Cox regression, and Kaplan-Meier curves. Primary outcomes were primary, primary assisted, and secondary patency rates, as well as limb salvage and survival rates. RESULTS: Over a 2-year period, 480 tibial interventions were completed for 421 patients. Eighty-seven percent (n = 418) of interventions were performed for critical limb ischemia (CLI) and 13% (n = 62) for claudication. The CLI cohort of 418 interventions was analyzed. These patients had a mean age of 71 years with a mean follow-up time of 16 ± 15 months (range, 0-59 months). Of the 418 interventions, 339 underwent percutaneous transluminal angioplasty (PTA): 333 PTA alone, six PTA + stent. The remaining 79 interventions received atherectomy: 33 laser, 13 directional, and 33 orbital either alone or in conjunction with PTA (11 atherectomy only, 68 atherectomy + PTA). The groups did not differ significantly in terms of demographics, risk factors, or technical success. The atherectomy group had more TASC B lesions (54% vs 38%; P = .013), while the PTA-alone group had more TASC D lesions (25% vs 13%; P = .004). TASC A and C lesions did not differ significantly between the groups. No significant differences existed with respect to the early (30-day) outcomes of loss of patency (11% vs 13%; P = .699), complications (8% vs 13%; P = .292), or major amputation (17% vs 13%; P = .344) in the PTA-alone group vs the atherectomy-assisted group. Kaplan-Meier analysis revealed no difference for all primary outcomes of PTA alone vs the atherectomy-assisted group at 12 and 36 months: primary patency (69%, 55% vs 61%, 46%; P = .158), primary assisted patency (83%, 71% vs 85%, 67%; P = .801), secondary patency (94%, 89% vs 95%, 89%; P = .892), limb salvage (79%, 70% vs 81%, 77%; P = .485), or survival (77%, 56% vs 80%, 50%; P = .944). CONCLUSIONS: The adjunctive use of atherectomy offered no improvement in primary outcomes over PTA alone in either early or late outcomes in CLI patients who underwent endovascular tibial interventions. Considering the additional cost and increased procedural time, these findings put into question the routine use of adjunctive atherectomy.
Asunto(s)
Angioplastia de Balón , Aterectomía , Isquemia/terapia , Enfermedad Arterial Periférica/terapia , Arterias Tibiales/cirugía , Anciano , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Angioplastia de Balón/mortalidad , Aterectomía/efectos adversos , Aterectomía/mortalidad , Constricción Patológica , Enfermedad Crítica , Femenino , Humanos , Isquemia/mortalidad , Isquemia/fisiopatología , Isquemia/cirugía , Estimación de Kaplan-Meier , Recuperación del Miembro , Masculino , Análisis Multivariante , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/cirugía , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Stents , Arterias Tibiales/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Lateral shuffle and side cut (SSC) movements are defensive basketball movements where movement speed is critical to performance. The purpose of this study was to compare SSC data obtained using timing lights with motion capture system data and to determine the most appropriate method for measuring SSC performance. Shuffle time data were recorded using both timing lights and a motion capture system while 9 male subjects performed 2 different SSC movement sets, with and without controlling for arm movements, which may influence performance times. Shuffle and side cut times and SSC displacements were used to calculate mean shuffle velocity for each trial. The SEs for the motion capture system were estimated for SSC times (± 4.2 milliseconds; ~0.24% of mean shuffle time) and velocities (± 5.5 mm · s; ~0.24% of mean shuffle velocity), respectively, indicating high levels of precision. Timing light movement time variability was significantly higher during the uncontrolled (SD = 42 milliseconds) when compared with the controlled (SD = 9 milliseconds, p < 0.001) condition, indicating a significant reduction in variability by controlling non-performance-related variability such as arm movement. A significant positive correlation was found between SSC time and SSC displacement (r = 0.42) indicating that performance times were dependent on displacement. Furthermore, the variance in motion-captured SSC velocity was significantly smaller than the variance in velocity determined using timing lights (p < 0.05). We concluded that motion-captured SSC velocity data reduced systematic errors and non-performance-related movement variability and, therefore, was better able to reflect true performance. As true performance variability in human movement provides important information, the presented method for calculating SSC velocity in this study is recommended for assessing SSC performance.
Asunto(s)
Baloncesto/fisiología , Recolección de Datos/métodos , Movimiento/fisiología , Grabación en Video , Adulto , Brazo/fisiología , Fenómenos Biomecánicos , Humanos , Imagenología Tridimensional , Masculino , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
Folie à deux - Thrombosis and Infections Abstract: Although infections are not represented in the Revised Geneva or Wells score, they increase the risk of venous thromboembolism (VTE) similarly to the known risk factors (immobilization, major surgery, active neoplasia). This increased risk of VTE can persist for six to twelve months after infection; moreover, the more severe the infection, the higher the risk of VTE may be. In addition to VTEs, infections can promote arterial thromboembolism. For example, 20% of pneumonias are accompanied by an acute cardiovascular event (acute coronary syndrome, heart failure, atrial fibrillation). In the case of infection-associated atrial fibrillation, the CHA2DS2 VASc score remains an appropriate guide for the indication of anticoagulation.
Asunto(s)
Fibrilación Atrial , Trastorno Paranoide Compartido , Accidente Cerebrovascular , Trombosis , Tromboembolia Venosa , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Medición de Riesgo , Trastorno Paranoide Compartido/complicaciones , Factores de Riesgo , Anticoagulantes/efectos adversos , Accidente Cerebrovascular/complicacionesRESUMEN
Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Zinc(II) complexes with dangling functional organic groups were synthesized by reaction of zinc acetate with a series of bifunctional p-substituted benzene derivatives (a combination of carboxylate, oximate, amino, ß-ketoimine, and salicylaldime groups). Selective coordination to carboxylate groups was observed when the second functional group was an oxime or ß-ketoimine group. When the second group was an amine or salicylaldimine moiety, these groups were additionally coordinated. From the reaction with p-aminobenzoic acid, the compound [Zn2(OOCCH3)(OOC-C6H4-NH2)3]∞ was crystallized. It is a three-dimensional coordination polymer with bridging aminobenzoate ligands.
RESUMEN
The prognostic performance of PREDICT in patients with HER2-positive early breast cancer (EBC) treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies is unclear. Therefore, we investigated its prognostic performance using data extracted from ALTTO, a phase III trial evaluating adjuvant lapatinib ± trastuzumab vs. trastuzumab alone in patients with HER2-positive EBC. Our analysis included 2794 patients. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT underestimated 5-year OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups, including those according to the type of anti HER2-therapy. The highest absolute differences were observed for patients with hormone receptor negative-disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively). AUC under the ROC curve was 73.7% (95% CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analyzed subgroups. In conclusion, our analysis showed that PREDICT highly underestimated OS in HER2-positive EBC. Hence, it should be used with caution to give prognostic estimation to HER2-positive EBC patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.
RESUMEN
Reaction of Y(5)O(OiPr)(13) ("yttrium iso-propoxide") with one molar equivalent of isopropyl acetoacetate (iprac) per Y resulted in the formation of Y(9)O(OH)(9)(OiPr)(8)(iprac)(8), a rare example of an yttrium alkoxo/hydroxo/oxo cluster. Reaction in a 1:3 molar ratio gave Y(4)(OH)(2)(iprac)(10) and Y(6)(OH)(6)(iprac)(12) instead. A fourth cluster, Y(9)O(OH)(9)(iprac)(16), structurally closely related to Y(9)O(OH)(9)(OiPr)(8)(iprac)(8), was obtained upon recrystallization of Y(4)(OH)(2)(iprac)(10) from CDCl(3).
RESUMEN
BACKGROUND: Skin rash and diarrhoea are known side-effects of pertuzumab. Studies with other anti-HER2 agents suggested that adverse events correlate with patient outcomes. In this exploratory cohort of patients with metastatic HER2-positive breast cancer included in the CLEOPATRA trial we evaluated the value of rash and diarrhoea as prognostic markers and as predictors of pertuzumab benefit. METHODS: This is a retrospective analysis of the multicenter, prospective, randomised CLEOPATRA trial. We defined two analytic cohorts: cohort 1 (C1) included patients from treatment initiation, and cohort 2 (C2) included patients after discontinuation of docetaxel. A landmark analysis was introduced to deal with immortal-time bias. Study endpoints were progression-free survival (PFS) and overall survival (OS). Univariable and multivariable Cox proportional hazards models were used. RESULTS: Of the 808 patients and after application of the landmark analysis, C1 and C2 included 777 and 518 patients, respectively. In C1, rash occurred in 271 patients (34.9%) and diarrhoea in 470 (60.5%). Rash was prognostic for PFS and OS (C1: adjusted hazard ratio [aHR] = 0.66 [95% CI = 0.48-0.91], p = 0.010]; C2: aHR 0.52 [95% CI = 0.30-0.89], p = 0.018) in both cohorts, while diarrhoea was only prognostic for PFS in cohort 2 (aHR = 0.65 [95% CI = 0.46-0.91], p = 0.011). Rash and diarrhoea were not predictive of pertuzumab benefit (in terms of PFS/OS) in the two cohorts. CONCLUSIONS: In patients treated with pertuzumab, trastuzumab, and docetaxel, rash is prognostic whenever it occurs during treatment, while diarrhoea only has prognostic value when occurring after docetaxel discontinuation. However, neither rash nor diarrhoea predict pertuzumab benefit.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/mortalidad , Diarrea/mortalidad , Exantema/mortalidad , Receptor ErbB-2/metabolismo , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Diarrea/inducido químicamente , Diarrea/patología , Exantema/inducido químicamente , Exantema/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We demonstrate "depth of field multiplexing" by a high resolution spatial light modulator (SLM) in a Fourier plane in the imaging path of a standard microscope. This approach provides simultaneous imaging of different focal planes in a sample with only a single camera exposure. The phase mask on the SLM corresponds to a set of superposed multi-focal off-axis Fresnel lenses, which sharply image different focal planes of the object to non-overlapping adjacent sections of the camera chip. Depth of field multiplexing allows to record motion in a three dimensional sample volume in real-time, which is exemplarily demonstrated for cytoplasmic streaming in plant cells and rapidly swimming protozoa.
Asunto(s)
Euglena/citología , Microscopía/métodos , Tradescantia/citología , Corriente Citoplasmática , Flores/citologíaRESUMEN
We describe the implementation of quantitative Differential Interference Contrast (DIC) Microscopy using a spatial light modulator (SLM) as a flexible Fourier filter in the optical path. The experimental arrangement allows for the all-electronic acquisition of multiple phase shifted DIC-images at video rates which are analyzed to yield the optical path length variation of the sample. The resolution of the technique is analyzed by retrieving the phase profiles of polystyrene spheres in immersion oil, and the method is then applied for quantitative imaging of biological samples. By reprogramming the diffractive structure displayed at the SLM it is possible to record the whole set of phase shifted DIC images simultaneously in different areas of the same camera chip. This allows for quantitative snap-shot imaging of a sample, which has applications for the investigation of dynamic processes.
Asunto(s)
Luz , Microscopía de Interferencia/instrumentación , Microscopía de Interferencia/métodos , Forma de la Célula , Cromosomas/ultraestructura , Diseño de Equipo , Eritrocitos/citología , Análisis de Fourier , Holografía/métodos , Microesferas , Modelos Teóricos , Poliestirenos , Programas InformáticosRESUMEN
We propose a full-field low-coherence interference (LCI) microscope that can provide different contrast modes using Fourier-plane filtering by means of a spatial light modulator. By altering the phase and spatial frequencies of the backreflected wavefront from the sample arm of the interferometer, we are able to change the contrast in the depth-resolved LCI images. We demonstrate that different types of contrast modes, such as, e.g., spiral phase contrast, can successfully be emulated to provide specific enhancement of internal structures and edges and to reveal complementary details within the samples under investigation.