CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Environmental and economic assessment of biodegradable and compostable alternatives for plastic materials in greenhouses.

Plastics and other materials commonly used in horticulture for plant support (e.g. raffia) and soil protection (e.g. mulching film) pose a challenge to achieving a circular economy. These materials contaminate plant residues, hampering their direct reuse due to the need for separation and cleaning. As a result, contaminated plant residues is often landfilled or incinerated. This study investigates the replacement of conventional plastic raffia and mulching film with biodegradable and compostable alternatives. Polypropylene raffia is compared with a biodegradable viscose polymer and compostable jute fibre, while polyethylene mulching film is compared with a biodegradable polylactic acid film. Conventional and novel alternatives are compared economically using Life-Cycle Costing and environmentally using Life-Cycle Assessment. The economic assessment is based on case studies with two horticultural companies in Almeria (south-eastern Spain), while the environmental analysis uses data from the Ecoinvent database. The use of biodegradable and compostable alternatives for raffia and mulching film proved to be 49% more expensive than conventional options. However, when conventional plastic waste is incinerated rather than landfilled, biodegradable and compostable alternatives have a lower carbon footprint. Although biodegradable and compostable options can be more expensive and have higher impacts in certain situations, proper waste management can lead to environmental benefits. With optimisation and incentives, these alternative options support the transition of horticulture to a sustainable circular economy.

Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.

BACKGROUND AND OBJECTIVES: Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality. METHODS: We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster. RESULTS: From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters. SIGNIFICANCE: Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults.

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.8 × 106 or 2.7 × 106 PfSPZ, of PfSPZ Vaccine, or normal saline administered at 8-week intervals in a randomized, double-blind, placebo-controlled trial stratified by age (6-11 months and 1-5, 6-10, 11-17, 18-35, and 36-61 years). All doses were successfully administered. In all, 192/207 injections (93%) in those aged 6-61 years were rated as causing no or mild pain. There were no significant differences in solicited adverse events (AEs) between vaccinees and controls in any age group (P ≥ 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine.

An α-chloroaldehyde-based formal synthesis of eribulin.

Eribulin (Halaven) is the most structurally complex non-peptidic drug made by total synthesis and has challenged preconceptions of synthetic feasibility in drug discovery and development. However, despite decades of research, the synthesis and manufacture of eribulin remains a daunting task. Here, we report syntheses of the most complex fragment of eribulin (C14-C35) used in two distinct industrial routes to this important anticancer drug. Our convergent strategy relies on a doubly diastereoselective Corey-Chaykovsky reaction to affect the union of two tetrahydrofuran-containing subunits. Notably, this process relies exclusively on enantiomerically enriched α-chloroaldehydes as building blocks for constructing the three densely functionalized oxygen heterocycles found in the C14-C35 fragment and all associated stereocenters. Overall, eribulin can now be produced in a total of 52 steps, which is a significant reduction from that reported in both academic and industrial syntheses.

COVID-19: una revisión radiológica en medio de la pandemia / COVID-19: a radiological review in the middle of the pandemic

Resumen La actual pandemia SARS-CoV-2 ha cambiado nuestra manera de trabajar y relacionarnos. Fue notificada en Wuhan, provincia de Hubei, en China, en diciembre de 2019. Habían existido dos brotes previos importantes de Coronavirus: el SARS, en 2002-2003 y el MERS, en 2012. Este artículo pretende ser una breve revisión acerca de algunos aspectos de la infección COVID-19 desde los aspectos fisiopatológicos, hallazgos por imagen y de las principales indicaciones de las pruebas de imagen, si bien estas siempre serán individualizadas. Tampoco podemos dejar de lado la posibilidad de que algunos de estos pacientes presente una evolución a fibrosis pulmonar. Finalmente, mencionaremos algunas recomendaciones para protegernos en nuestro puesto de trabajo.

Abstract The current SARS-CoV-2 pandemic has changed the way we work and interact. It was notified in Wuhan, Hubei province, China, in December 2019. There had been two previous major outbreaks of Coronavirus: SARS in 2002-2003 and MERS in 2012. This article aims to be a brief review of some aspects of the COVID-19 infection from the pathophysiological aspects, imaging findings, as well as the main indications for the imaging, although these will always be individualized. We cannot ignore the possibility that some of these patients may present evolution to pulmonary fibrosis. Finally, we will mention some recommendations to protect ourselves in our workplace.

Transfusion-Related Acute Lung Injury (TRALI) in Postoperative Anesthesia Care Unit (PACU) After One Unit of Platelets: A Case Report.

Transfusion-related acute lung injury (TRALI) following transfusion of all plasma-containing blood products is a rare but serious syndrome characterized by the acute onset of non-cardiogenic pulmonary edema with severe hypoxemia with or without symptoms of hypotension, pinkish frothy secretions, fever, and cyanosis. In this report, we present a case of a 66-year-old female with a medical history significant for hypertension, hyperlipidemia, hepatitis C, liver cirrhosis, tobacco use disorder, metastatic spindle cell carcinoma of the lung status post chemotherapy who developed TRALI after administration of one unit of platelets. Although a rare occurrence, there can be a considerable risk of TRALI following transfusion of all plasma-containing blood products and there is great importance in considering each patient's risk factors for TRALI development prior to blood product administration.

Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis.

PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.

Long term oral health related quality of life after TMJ arthrocentesis with hyaluronic acid. A retrospective cohort study.

The purpose of the study was to assess the long-term oral health-related quality of life (oQoL) in patients with temporomandibular joint (TMJ) internal derangement (ID) after TMJ arthrocentesis plus hyaluronic acid (HA). Patients were analysed at different follow-up times using an analytical observational design. The Oral Health Impact Profile-14 (OHIP-14) score was evaluated according to age, sex, disc position, presence of degenerative joint disease (DJD), joint pain, maximum mouth opening and follow-up time. A total of 60 participants were enrolled, 88% female, with a mean age of 38 years (SD = 13.48). In an average follow-up of 25.02 months (SD = 5.32), the OHIP-14 total score decreased 8.67 (95% confidence interval [CI]: -11.21 to -6.11) after the intervention (Cohen's d = 1.22; 95% CI = 0.81 to 1.64). All OHIP-14 domain scores decreased (p < 0.05) except for the Functional limitation domain (p = 0.378). The oQoL after the intervention worsened in female patients (p = 0.039) and with a higher level of pain at baseline (p = 0.002). Self-perceived QoL improvement should be considered stable long term after temporomandibular joint arthrocentesis plus HA, regardless of concurrence with DJD or ID subtype. QoL should be used as clinical assessment measure of ID patients, with special attention to those with higher levels of pain.

Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL.

This open-label, multicenter, single-arm, phase 2 study assessed the safety and efficacy of blinatumomab consolidation therapy in adult patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL; International Prognostic Index 3-5 and/or double-/triple-hit or double MYC/BCL-2 expressors) who achieved complete response (CR), partial response (PR), or stable disease (SD) following run-in with 6 cycles of R-chemotherapy (NCT03023878). Of the 47 patients enrolled, 28 received blinatumomab. Five patients (17.9%) experienced grade 4 treatment-emergent adverse events of interest (neutropenia, n = 4; infection, n = 1). Two deaths reported at the end of the study were unrelated to treatment with blinatumomab (disease progression, n = 1; infection, n = 1). 3/4 patients with PR and 4/4 patients with SD after R-chemotherapy achieved CR following blinatumomab. Consolidation with blinatumomab in patients with newly diagnosed, high-risk DLBCL who did not progress under R-chemotherapy was better tolerated than in previous studies where blinatumomab was used for treatment of patients with lymphoma.

Factores de riesgos socio-ambientales asociados al diagnóstico precoz del cáncer de labio en Camagüey

RESUMEN El trabajo constituye un análisis de los diferentes factores que interfieren en el diagnóstico precoz del cáncer de labio en la población de Camagüey. Se realizó un estudio descriptivo y transversal, desde la perspectiva del enfoque Ciencia, Tecnología y Sociedad, que incluyó a todos los pacientes diagnosticados con la enfermedad en el período comprendido de enero del 2015 a diciembre del 2020.Se describen los factores socio ambientales que juegan el papel más importante en el origen de las neoplasias de labio que pueden ser modificados desde la comunidad.

ABSTRACT The work constitutes an analysis of the different factors that interfere in the early diagnosis of lip cancer in the population of Camagüey. A descriptive and cross-sectional study was carried out, from the perspective of the Science, Technology and Society approach, which included all patients diagnosed with the disease in the period from January 2015 to December 2020.The socio-environmental factors that play the most important role in the origin of lip neoplasms that can be modified from the community are described.

Transplant: The Success of Renal Transplant Programs.

In the absence of malignancy or other severe comorbidity, kidney transplantation offers better survival rates and quality of life than dialysis. Despite this survival advantage, many lower- and upper-middle-income countries do not offer adequate kidney transplant services. This is particularly troubling because end-stage kidney disease often is more common in these countries than in high-income countries and overall is less costly in the life of a patient. We describe the contrasting levels of provision of kidney transplantation in Mexico, India, Nigeria, Ghana, and Zimbabwe, and kidney transplant services for children in Africa.

Metástasis cutáneas como primera manifestación de neuroblastoma primario de glándula suprarrenal en un paciente pediátrico / Cutaneous metastasis as the first manifestation of primary adrenal gland neuroblastoma in a pediatric patient

Resumen Introducción: El neuroblastoma es el tumor maligno más frecuente en el primer año de vida y el tumor sólido extracraneal más frecuente en la infancia. Solo el 1% de los casos debuta con metástasis cutáneas, caracterizadas por nódulos azulados subcutáneos. Se presenta el caso de un lactante con un neuroblastoma suprarrenal izquierdo en el que las metástasis cutáneas constituían el síntoma principal. Caso clínico: Lactante de sexo femenino, de 2 meses de edad, sin antecedentes de importancia para el padecimiento actual. Acudió por presentar dermatosis diseminada en la región cervical y occipital, el abdomen, el muslo derecho y el pie izquierdo. La dermatosis se caracteriza por nódulos subcutáneos, sólidos, bien delimitados, < 1 cm, de color azulado, que iniciaron su aparición a los 7 días de vida en el hipocondrio derecho, con crecimiento progresivo, asintomáticos. Se realizó biopsia de un nódulo y se reportó la presencia de células pequeñas con núcleo denso hipercromático, escaso citoplasma y dispuestas en nidos. La inmunohistoquímica fue positiva para cromogranina y enolasa neuronal específica. Los hallazgos fueron compatibles con metástasis cutánea de neuroblastoma. Se solicitó valoración y abordaje por oncología pediátrica, que reportó un estadio 4 de la enfermedad y se inició el tratamiento correspondiente. Conclusiones: Los pediatras y los dermatólogos pediatras son los primeros en atender a niños con alguna lesión cutánea. Se deben tener en cuenta las metástasis cutáneas, que pueden aparecer antes o simultáneamente al diagnóstico de un tumor primario. Por lo tanto, se debe realizar un correcto abordaje con el fin de mejorar el pronóstico y la calidad de vida del paciente.

Abstract Background: Neuroblastoma is the most common malignant tumor in the first year of life and the most common extracranial solid tumor in childhood. Only 1% of cases present with cutaneous metastases characterized by subcutaneous bluish nodules. We report the case of an infant with a left adrenal neuroblastoma in whom skin metastases were the main symptom. Case report: Two-month-old female infant with no relevant history for the current condition. The infant presented disseminated dermatosis affecting the head in the cervical and occipital region, abdomen, right thigh and left foot. Dermatosis was characterized by subcutaneous nodules, solid, well limited, < 1 cm, bluish color that appeared at 7 days of life in the right upper quadrant, with progressive growth, asymptomatic. A biopsy of a nodule was performed, which reported the presence of small cells with a dense hyperchromatic nucleus, scarce cytoplasm, arranged in nests. Immunohistochemistry was positive for chromogranin and specific neuronal enolase. Findings were consistent with cutaneous neuroblastoma metastasis. An assessment and approach by pediatric oncology were requested, reporting disease stage 4 and initiating the corresponding treatment. Conclusions: Pediatricians and pediatric dermatologists are the first to attend to children with a skin lesion. We must consider that skin metastases may appear prior to or simultaneously with the diagnosis of a primary tumor. Therefore, we should carry out a correct approach in order to improve the prognosis and the quality of life of the patient.

Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.

BACKGROUND: HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors. METHODS: A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made. RESULTS: One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4+ T cells count < 200 cells/µL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7. CONCLUSIONS: Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.

The sum of kidney donor profile index and estimated post-transplant survival scale and their correlation with egfr decline in deceased donor kidney recipients

Background: The impact of donor quality on post-kidney transplant survival may vary by candidate condition. Objective: Analyzing the combined use of the Kidney Donor Profile Index (KDPI) and the estimated post-transplant survival (EPTS) scale and their correlation with the estimated glomerular filtration rate (eGFR) decline in deceased-donor kidney recipients (DDKR). Methods: This was a retrospective, observational cohort study. We included DDKRs between 2015 and 2017 at a national third-level hospital. Results: We analyzed 68 DDKR. The mean age at transplant was 41 ± 14 years, 47 (69%) had sensitization events, 18 (26%) had delayed graft function, and 16 (23%) acute rejection. The graft survival at 12 and 36 months was 98.1% (95% CI 94-100) and 83.7% (95% CI 65-100), respectively. The Pearson correlation coefficient between the percentage reduction in the annual eGFR and the sum of EPTS and KDPI scales was r = 0.61, p < 0.001. The correlation coefficient between the percentage reduction in the annual eGFR and the EPTS and KDPI scales separately was r = 0.55, p < 0.001, and r = 0.53, p < 0.001, respectively. Conclusions: The sum of EPTS and KDPI scales can provide a better donor-recipient relationship and has a moderately positive correlation with the decrease in eGFR in DDKR.

[Cutaneous metastasis as the first manifestation of primary adrenal gland neuroblastoma in a pediatric patient.] / Metástasis cutáneas como primera manifestación de neuroblastoma primario de glándula suprarrenal en un paciente pediátrico

Introducción: El neuroblastoma es el tumor maligno más frecuente en el primer año de vida y el tumor sólido extracraneal más frecuente en la infancia. Solo el 1% de los casos debuta con metástasis cutáneas, caracterizadas por nódulos azulados subcutáneos. Se presenta el caso de un lactante con un neuroblastoma suprarrenal izquierdo en el que las metástasis cutáneas constituían el síntoma principal. Caso clínico: Lactante de sexo femenino, de 2 meses de edad, sin antecedentes de importancia para el padecimiento actual. Acudió por presentar dermatosis diseminada en la región cervical y occipital, el abdomen, el muslo derecho y el pie izquierdo. La dermatosis se caracteriza por nódulos subcutáneos, sólidos, bien delimitados, < 1 cm, de color azulado, que iniciaron su aparición a los 7 días de vida en el hipocondrio derecho, con crecimiento progresivo, asintomáticos. Se realizó biopsia de un nódulo y se reportó la presencia de células pequeñas con núcleo denso hipercromático, escaso citoplasma y dispuestas en nidos. La inmunohistoquímica fue positiva para cromogranina y enolasa neuronal específica. Los hallazgos fueron compatibles con metástasis cutánea de neuroblastoma. Se solicitó valoración y abordaje por oncología pediátrica, que reportó un estadio 4 de la enfermedad y se inició el tratamiento correspondiente. Conclusiones: Los pediatras y los dermatólogos pediatras son los primeros en atender a niños con alguna lesión cutánea. Se deben tener en cuenta las metástasis cutáneas, que pueden aparecer antes o simultáneamente al diagnóstico de un tumor primario. Por lo tanto, se debe realizar un correcto abordaje con el fin de mejorar el pronóstico y la calidad de vida del paciente.

Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial.

BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.

Reliability of Bystander Recognition of Clinical Features in Pre-Hospital Classification of Acute Cerebrovascular Syndromes: Preliminary Findings

ABSTRACT Background: The recognition of stroke symptoms by patients or bystanders directly affects the outcomes of patients with acute cerebrovascular disease. Objective: The objective of the study was to assess the predictive value of the medical history and clinical features recognized by the patients’ bystanders to classify neurovascular syndromes in pre-hospital settings. Methods: We included 150 stroke patients of two Mexican referral centers: 50 with acute ischemic stroke (AIS), 50 with intracerebral hemorrhage (ICH), and 50 with subarachnoid hemorrhage (SAH). The performance of clinical prediction rules (CPR) to identify the stroke types was evaluated with features recognized by the patients’ bystanders before hospital arrival. The impact of CPRs on early arrival and in-hospital mortality was also analyzed. Results: Overall, 72% of the patients had previous medical evaluations in other centers before final referral to our hospitals, and therefore, only 45% had a final onset-to-door time <6 h, even when the first medical assessment had occurred in ≤1 h in 75% of cases. Clinical features noticed by the patients’ bystanders had low positive predictive values (PPV) for any stroke type. The CPR “language or speech disorder + focal motor deficit” had 93% sensitivity and a negative predictive value (NPV) of 84% to distinguish AIS. In SAH, headache alone showed a sensitivity of 84% and NPV of 97%. No CPR had an adequate performance on ICH. CPRs were not associated with final onset-to-door time. Altered consciousness, age ≥65 years, indirect arrival with stops before final referral, and atrial fibrillation increased in-hospital mortality. Conclusion: Clinical features referred by the witness of a neurovascular emergency have limited PPV, but adequate NPV in ruling-out AIS and SAH among stroke types. The use of CPRs had no impact on onset-to-door time or in-hospital mortality when the final arrival to a third-level center occurs with previous medical referrals.