Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170.

Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3 weeks for up to 35 cycles (∼2 years) in patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL) whose disease progressed after or who were ineligible for autologous stem cell transplantation. The end points included objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) according to the investigator per 2007 Response Criteria; overall survival (OS); and safety. In this final analysis, median duration of follow-up was 48.7 months (range, 41.2-56.2). The ORR was 41.5% (complete response, 20.8%; partial response, 20.8%). The median DOR was not reached; no patients who achieved a complete response progressed at the data cutoff. The median PFS was 4.3 months; the 4-year PFS rate was 33.0%. The median OS was 22.3 months; the 4-year OS rate was 45.3%. At the data cutoff, 30 patients (56.6%) had any-grade treatment-related adverse events (AEs); the most common were neutropenia, asthenia, and hypothyroidism. Grade 3/4 treatment-related AEs occurred in 22.6% of the patients; no grade 5 AEs occurred. After 4 years of follow-up, pembrolizumab continued to provide durable responses, with promising trends for long-term survival and acceptable safety in R/R PMBCL.

Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage. / Evaluación de los costes asociados a la enfermedad de pacientes con linfoma cutáneo de células T en España: análisis en función del estadio clínico (estudio MICADOS).

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

[Translated article] Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage.

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO.

Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.

Simulating carbon accumulation and loss in the central Congo peatlands.

Peatlands of the central Congo Basin have accumulated carbon over millennia. They currently store some 29 billion tonnes of carbon in peat. However, our understanding of the controls on peat carbon accumulation and loss and the vulnerability of this stored carbon to climate change is in its infancy. Here we present a new model of tropical peatland development, DigiBog_Congo, that we use to simulate peat carbon accumulation and loss in a rain-fed interfluvial peatland that began forming ~20,000 calendar years Before Present (cal. yr BP, where 'present' is 1950 CE). Overall, the simulated age-depth curve is in good agreement with palaeoenvironmental reconstructions derived from a peat core at the same location as our model simulation. We find two key controls on long-term peat accumulation: water at the peat surface (surface wetness) and the very slow anoxic decay of recalcitrant material. Our main simulation shows that between the Late Glacial and early Holocene there were several multidecadal periods where net peat and carbon gain alternated with net loss. Later, a climatic dry phase beginning ~5200 cal. yr BP caused the peatland to become a long-term carbon source from ~3975 to 900 cal. yr BP. Peat as old as ~7000 cal. yr BP was decomposed before the peatland's surface became wetter again, suggesting that changes in rainfall alone were sufficient to cause a catastrophic loss of peat carbon lasting thousands of years. During this time, 6.4 m of the column of peat was lost, resulting in 57% of the simulated carbon stock being released. Our study provides an approach to understanding the future impact of climate change and potential land-use change on this vulnerable store of carbon.

Autologous stem cell transplantation (ASCT) in patients with mantle cell lymphoma: a retrospective study of the Spanish lymphoma group (GELTAMO).

Guidelines recommend autologous stem cell transplantation (ASCT) consolidation in first complete or partial response after regimens including rituximab (R) and high-dose AraC (HDAC), but its use beyond that response is questioned. We present a retrospective analysis of 268 patients with MCL who received ASCT. With a median follow-up for survival patients of 54 months, progression-free survival and overall survival for the whole series were 38 and 74 months, respectively, and for patients transplanted in first CR 49 and 97 months, respectively. Patients without CR before transplant were analyzed separately, those who achieved CR after transplantation had better PFS (48 vs 0.03 months, p < 0.001) and OS (92 vs 16 months, p < 0.001) than the remaining. In univariate analysis, first CR at transplant (p = 0.01) and prior rituximab (p = 0.02) were the variables associated with PFS. For OS, the same variables resulted significant (p = 0.03 and p < 0.001, respectively). In multivariate analysis, only the status at transplant (first CR) remained significant. This retrospective study concludes that ASCT consolidation in first CR induces high survival rates. In other stages of disease, the need of ASCT as consolidation may be questioned.

Diagnostic performance of the measurement of nitric oxide in exhaled air in the diagnosis of COPD phenotypes.

INTRODUCTION: COPD is a highly heterogeneous disease that has a serious impact on affected populations. Patients share some of the features of bronchial asthma, often summarized under the term ACOS (asthma-COPD overlap syndrome). The objective of this study is to evaluate the utility of the measurement of nitric oxide in exhaled air (FENO50) in the diagnosis of COPD phenotypes. MATERIAL AND METHODS: The study comprised cross-sectional observation of patients receiving assistance during a respiratory outpatient visit. Patient data was collected on lung function, FENO, questionnaires scoring CAT®(COPD Assessment Test), and COPD clinical phenotype. RESULTS: 192 patients were studied: 103 with COPD; 16 healthy non-smokers; 30 healthy smokers; and 43 asthmatics. COPD patients were grouped by phenotype: 34 non exacerbators (33.0%); 22 ACOS (21.3%); 13 frequent exacerbators with emphysema (12.6%); and 34 frequent exacerbators with chronic bronchitis (33.0%). ACOS patients showed significantly higher FENO50 values compared to the others after adjustments for confounding factors. FENO50 demonstrated greater diagnostic accuracy than the bronchodilator test (BT) in the diagnosis of ACOS and COPD phenotypes (AUC 0.79 vs 0.74), with an optimal cut-off value of 19 ppb (sensitivity 0.68, specificity 0.75). CONCLUSIONS: Patients with COPD have different levels of FENO50 depending on the COPD phenotype. FENO50 measurement provides better diagnostic accuracy than BT, with an optimal cut-off value of 19 ppb.

[Analysis of neutrophil gelatinase-associated lipocalin in the critical patient]. / Análisis de la lipocalina asociada a la gelatinasa de neutrófilos en el paciente crítico.

OBJECTIVE: To determine if NGAL value exceeding 150 ng/mL is a good diagnostic test for acute renal failure in critically ill patients. DESIGN: Prospective, observational cohort. SETTING: Intensive Care Unit and Cardiac Surgery Intensive Care Service at Hospital Germans Trias I Pujol. PARTICIPANTS: Patients admitted to the Intensive Care department the Designated days in the studio. INTERVENTIONS: Analysis of serum creatinine blood given from 7 days prior to the start of the study, and daily during 4 weeks and by determination of NGAL urine test in frozen sample, analyzer ARCHITECT (Abbott Diagnostics) determined by immunoassay the day baseline and 2 times a week for 4 weeks, analysis of the stay and mortality. RESULTS: A total of 529 NGAL samples were obtained from 46 patients. 37% of patients had a value of NGAL>150 ng/mL. The Sensivity of the test to diagnose acute renal failure was 69%, Specifity was 75,7%. However, the Positive Predictive Test Value was 53%, which means that 47% of patients with high NGAL did not develop AKI. A NGAL >150 mg/dL was associated with a significantly higher SOFA and a longer stay in the ICU. The mortality of patients with elevated NGAL was 58.8%. CONCLUSIONS: A NGAL>150 ng/mL does not seem to be an excellent test for AKI in critically ill patients but is associated with a worse prognosis.

Rescuers' characteristics associated with the correct chest compression during cardiopulmonary resuscitation.

AIM: To analyse the caregivers' physical, anthropometrical and educational characteristics associated with adequate chest compression and full chest recoil during cardiopulmonary resuscitation (CPR). METHODS: An observational prospective research study was conducted. Emergency and critical care health professionals and students performed two minutes of chest compressions on a dummy. Depth and residual leaning after the compressions were assessed and their association with several variables (physical, anthropometrical, and educational) was analysed using logistic regression models. RESULTS: Two hundred thirty-eight volunteers participated. Previous experience of the rescuer in less than six CPRs (OR = 3.03; 95% CI 1.2-7.63) was related to a higher probability of not achieving an adequate depth of compressions. Greater height (OR: .93; 95% CI .87-.99) and grip strength (OR: .94; 95% CI .89-.99) were associated with correct performance of chest compression. We did not find any characteristic related to chest recoil. CONCLUSIONS: The caregiver's previous experience with CPR was the strongest factor associated with adequate performance of chest compressions. To a lesser extent, the professional's height and upper body muscle strength also have an influence. No factors associated with the adequacy of full chest recoil were identified.

Tropical Peatland Hydrology Simulated With a Global Land Surface Model.

Tropical peatlands are among the most carbon-dense ecosystems on Earth, and their water storage dynamics strongly control these carbon stocks. The hydrological functioning of tropical peatlands differs from that of northern peatlands, which has not yet been accounted for in global land surface models (LSMs). Here, we integrated tropical peat-specific hydrology modules into a global LSM for the first time, by utilizing the peatland-specific model structure adaptation (PEATCLSM) of the NASA Catchment Land Surface Model (CLSM). We developed literature-based parameter sets for natural (PEATCLSMTrop,Nat) and drained (PEATCLSMTrop,Drain) tropical peatlands. Simulations with PEATCLSMTrop,Nat were compared against those with the default CLSM version and the northern version of PEATCLSM (PEATCLSMNorth,Nat) with tropical vegetation input. All simulations were forced with global meteorological reanalysis input data for the major tropical peatland regions in Central and South America, the Congo Basin, and Southeast Asia. The evaluation against a unique and extensive data set of in situ water level and eddy covariance-derived evapotranspiration showed an overall improvement in bias and correlation compared to the default CLSM version. Over Southeast Asia, an additional simulation with PEATCLSMTrop,Drain was run to address the large fraction of drained tropical peatlands in this region. PEATCLSMTrop,Drain outperformed CLSM, PEATCLSMNorth,Nat, and PEATCLSMTrop,Nat over drained sites. Despite the overall improvements of PEATCLSMTrop,Nat over CLSM, there are strong differences in performance between the three study regions. We attribute these performance differences to regional differences in accuracy of meteorological forcing data, and differences in peatland hydrologic response that are not yet captured by our model.

Impact of cadaveric practices on arthroscopic knee training for Orthopaedic Surgery and Traumatology residents. / Impacto de las prácticas cadavéricas en la formación artroscópica de rodilla de los residentes de Cirugía Ortopédica y Traumatología.

BACKGROUND AND OBJECTIVES: There currently is a considerable variability in the content of training programs and courses for orthopaedic surgeons in training. Besides this, there is still no consensus regarding which is the most effective methodology for improving learning of the technique or for its qualitative evaluation. A study was carried out to assess the influence of carrying out a cadaveric practical course on the acquisition of arthroscopic technical skills in fifth-year residents. MATERIAL AND METHODS: A knee arthroscopy cadaveric course was performed in which 48 students participated. Different technical aspects during a knee arthroscopy, as well as the residents skill and the execution time were evaluated before and after the course using a specific questionnaire. RESULTS: There was a significant statistic improvement between the initial and final evaluation, increasing from 11,7 till 17,1 (maximum 20) points. Also, a significant improvement in all the parameters analysed was observed; the identification of anatomic structures (p = 0.001), the palpation of specific structures (p = 0.032), and the time necessary for the arthroscopic knee check (p = 0.015). CONCLUSIONS: A knee arthroscopy cadaveric course improves significantly the technical skills of surgeons in training.

Rescuers' characteristics associated with the correct chest compression during cardiopulmonary resuscitation. / Características de los reanimadores asociadas a la correcta compresión torácica durante la reanimación cardiopulmonar.

AIM: To analyse the caregivers' physical, anthropometrical and educational characteristics associated with adequate chest compression and full chest recoil during cardiopulmonary resuscitation (CPR). METHODS: An observational prospective research study was conducted. Emergency and critical care health professionals and students performed two minutes of chest compressions on a dummy. Depth and residual leaning after the compressions were assessed and their association with several variables (physical, anthropometrical, and educational) was analysed using logistic regression models. RESULTS: Two hundred thirty-eight volunteers participated. Previous experience of the rescuer in less than six CPRs (OR: 3.03; CI 95%: 1.2-7.63) was related to a higher probability of not achieving an adequate depth of compressions. Greater height (OR: .93; 95% CI: .87-.99) and grip strength (OR: .94; 95% CI: .89-.99) were associated with correct performance of chest compression. We did not find any characteristic related to chest recoil. CONCLUSIONS: The caregiver's previous experience with CPR was the strongest factor associated with adequate performance of chest compressions. To a lesser extent, the professional's height and upper body muscle strength also have an influence. No factors associated with the adequacy of full chest recoil were identified.