Recent epidemiological trends in extrapulmonary TB in Galicia, Spain.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66-4.07). The most frequent age group was 15-44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0-14 years), 75% (15-44 years), 44% (45-64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Rethinking prognostic factors in locally advanced or metastatic urothelial carcinoma in the immune checkpoint blockade era: a multicenter retrospective study.

BACKGROUND: Few studies have investigated the safety and efficacy of anti-PD-(L)1 antibodies in metastatic urothelial carcinoma (mUC) in daily clinical practice. Knowledge about the influence of baseline clinical and analytical factors on therapy outcomes is scarce. PATIENTS AND METHODS: We conducted a multicenter retrospective study involving 119 previously treated or untreated mUC patients under anti-PD-(L)1 therapy in a real-world scenario. The objectives of this study were to confirm the safety and efficacy of anti-PD-(L)1 monotherapy and to identify pretreatment factors influencing therapy outcomes. In addition, an independent prognostic model for overall survival (OS) was developed and internally validated. RESULTS: Median OS was 7.8 months [95% confidence interval (CI), 5.4-10.4], median progression-free survival (PFS) was 2.80 months (95% CI, 2.4-3.4), disease control rate (DCR) was 40% (95% CI, 31-49), and overall response rate (ORR) was 24% (95% CI, 15-31). Presence of peritoneal metastases was associated with poor OS [hazard ratio (HR) = 2.40, 95% CI, 1.08-5.33; P = 0.03]. Use of proton-pump inhibitors (PPI) was associated with poor OS (HR = 1.83, 95% CI, 1.11-3.02; P = 0.02) and PFS (HR = 1.94, 95% CI, 1.22-3.09; P = 0.005), and lower DCR (OR = 0.38, 95% CI, 0.17-0.89; P = 0.03) and ORR (OR = 0.18, 95% CI, 0.02-1.60; P = 0.002). The three risk category prognostic model developed included Eastern Cooperative Oncology Group performance status, PPI use, albumin level, presence of liver metastases, and presence of peritoneal metastases variables and was associated with higher risk of death (HR = 3.00, 95% CI, 1.97-4.56; P = 0.0001). CONCLUSIONS: This study confirms anti-PD-(L)1 monotherapy as a safe and effective treatment option in daily clinical practice for mUC patients. It also describes the presence of peritoneal metastases as an independent prognostic factor for OS and underlines the association between PPI use and worse therapeutic outcomes. Finally, it proposes a new easy-to-use risk-assessment model for OS prediction.

Adherencia al tratamiento farmacológico del tabaquismo y factores predictores en un escenario no financiado / Adherence to pharmacological treatment of smoking and predictive factors in an unfunded scenario

Antecedentes y objetivo. Las intervenciones de des habituación basadas en el asesoramiento psicológicoy tratamiento farmacológico han demostrado ser las más eficaces para abandonar el tabaco. La terapia sustitutiva con nicotina, bupropión y vareniclina son lostratamientos farmacológicos de primera elección que han demostrado una mayor seguridad y eficacia, triplicando las posibilidades de cesación tabáquica. Sinembargo, en un escenario no financiado, el grado de adherencia a estos fármacos es bajo. Por todo ello, el objetivo del estudio es analizar la adherencia a dichosfármacos y los factores predictores de ella.Pacientes y métodos. Estudio transversal de una cohorte de 660 fumadores reclutados entre 2013 y 2017en un área sanitaria de Galicia incluidos en programas de deshabituación tabáquica. Se analizan las características de los pacientes y el porcentaje de adherenciaa los fármacos de cesación tabáquica.Resultados.Un 35% de los fumadores que acuden aconsultas de deshabituación tabáquica en nuestra áreasanitaria no retiran el fármaco previamente prescrito.Son factores predictores de adherencia a fármacos dedeshabituación tabáquica: estar en fase de preparación OR: 4,06 IC95% (1,58-6,39) p=0,003; realizarintentos previos de abandono en el último año OR:5,3 IC95% (1,3-7,1) p=0,016; uso de fármacos pre-viamente OR: 4,16 IC95 (1,7-6,2) p=0,0003; o elnúmero de consultas: OR: 1,6 IC95% (1,26-2,05)p=0,000.Conclusiones.La adherencia al tratamiento del tabaquismo es mejorable en nuestra área sanitaria. Lafase de abandono del fumador, los intentos previoscon tratamientos farmacológicos y la intensidad de la intervención son factores que se asocian a su implementación. (AU)

Backgrounds and objective. The smoking cessation interventions based on psychological advice and drugtreatment have been shown to be the most effectiveto stop smoking. Nicotine replacement therapy, bu-propion and varenicline are the drug treatments of first choice that have demonstrated better safety andefficacy, tripling the possibilities of smoking cessation.However, in an unfinanced setting, the degree of ad-herence to these drugs is low. Therefore, the objectiveof the study is to analyze adherence to said drugs andthe predictive factors of it.Patients and methods.Cross-sectional study of acohort of 660 smokers recruited between 2013 and2017 in a health care area of Galicia enrolled in smo-king cessation programs. The characteristics of thepatients and percentage of adherence to the smokingcessation drugs are analyzed.Results.A total of 35% of smokers who come to thesmoking cessation consultations in our health carearea do not obtain the previously prescribed drug.Predictive factors of adherence to smoking cessationdrugs are: being in the preparation phase: OR: 4.0695% CI (1.58-6.39) p=0.003, having made previousattempts to stop smoking in the last year: OR: 5.395% CI (1.3-7.1) p=0.016, previous use of drug: OR:4.16 95% CI (1.7-6.2) p=0.0003 or number of con-sultations: OR: 1.6 95% CI (1.26-2.05) p=0.000.Conclusions.Adherence to treatment of smoking ces-sation can be improved in our health care area. Thecessation phase of the smoker, previous attempts withdrug treatments and intensity of the intervention arethe factors associated to its implementation. (AU)

Evening chronotype, disordered eating behavior, and poor dietary habits in bipolar disorder.

OBJECTIVE: Our aim was to evaluate the relationship between evening chronotype, a proxy marker of circadian system dysfunction, and disordered eating behavior and poor dietary habits in individuals with bipolar disorder (BD). METHODS: In this cross-sectional study, we evaluated 783 adults with BD. Chronotype was determined using item 5 from the reduced Morningness-Eveningness Questionnaire. The Eating Disorder Diagnostic Scale (EDDS) and the Rapid Eating Assessment for Participants-Shortened Version (REAP-S) were used to assess disordered eating behavior and dietary habits respectively. General linear models and logistic regression models were utilized to evaluate differences between chronotype groups. RESULTS: Two hundred and eight (27%) BD participants self-identified as having evening chronotypes. Compared to non-evening types, evening types were younger (P < 0.01) and, after controlling for age, had higher mean EDDS composite z-scores (P < 0.01); higher rates of binge-eating (BE) behavior (P = 0.04), bulimia nervosa (P < 0.01), and nocturnal eating binges (P < 0.01); and a higher body mass index (P = 0.04). Compared to non-evening types, evening chronotypes had a lower REAP-S overall score (P < 0.01) and scored lower on the 'healthy foods' and 'avoidance of unhealthy food' factors. Evening types also skipped breakfast more often (P < 0.01), ate less fruit (P = 0.02) and vegetables (P = 0.04), and consumed more fried foods (P < 0.01), unhealthy snacks (P = 0.02), and soft drinks (P = 0.01). CONCLUSIONS: Our findings suggest that the circadian system plays a role in the disordered eating and unhealthy dietary behaviors observed in BD patients. The circadian system may therefore represent a therapeutic target in BD-associated morbidity that warrants further investigation.

A new scenario in metastatic renal cell carcinoma: a SOG-GU consensus.

BACKGROUND: This article describes and compares approved targeted therapies and the newer immunotherapy agents. MATERIALS AND METHODS: This article especially performs an in-depth review of currently available data for tivozanib, explaining its mechanism of action, its safety profile and its role as an efficacy drug in the management of renal cancer. RESULTS: Despite the fact that the treatment of advanced RCC has been dramatically modified in recent years, durable remissions are scarce and it remains a lethal disease. For first- and second-line therapy, there is now growing evidence to guide the selection of the appropriate treatment. CONCLUSIONS: Several TKIs are standard of care at different settings. Among those approved TKIs, tivozanib has similar efficacy than others with a better safety profile. The use of prognostic factors is critical to the selection of optimal therapy.

Chemotherapy management for unfit patients with metastatic castration-resistant prostate cancer.

Administration of chemotherapy in prostate cancer depends on patient fitness. In unfit patients, physiological impairment determines the optimum treatment. Although no consensus on assessing patient fitness currently exists, this article proposes an algorithm combining the available information for administering chemotherapy, and in particular docetaxel, in unfit patients. It was constructed by reviewing factors that can influence treatment, such as performance status, taxane-related comorbidities and nutritional status. Geriatric scales for prostate cancer patients and alternative treatment regimens for this population are also reviewed. In summary, patients require overall assessment to optimise treatment. Use of docetaxel should be restricted in unfit patients, and other options must be evaluated, because of high toxicity and low efficacy.

Diaphragmatic dysfunction.

The diaphragm is the main breathing muscle and contraction of the diaphragm is vital for ventilation so any disease that interferes with diaphragmatic innervation, contractile muscle function, or mechanical coupling to the chest wall can cause diaphragm dysfunction. Diaphragm dysfunction is associated with dyspnoea, intolerance to exercise, sleep disturbances, hypersomnia, with a potential impact on survival. Diagnosis of diaphragm dysfunction is based on static and dynamic imaging tests (especially ultrasound) and pulmonary function and phrenic nerve stimulation tests. Treatment will depend on the symptoms and causes of the disease. The management of diaphragm dysfunction may include observation in asymptomatic patients with unilateral dysfunction, surgery (i.e., plication of the diaphragm), placement of a diaphragmatic pacemaker or invasive and/or non-invasive mechanical ventilation in symptomatic patients with bilateral paralysis of the diaphragm. This type of patient should be treated in experienced centres. This review aims to provide an overview of the problem, with special emphasis on the diseases that cause diaphragmatic dysfunction and the diagnostic and therapeutic procedures most commonly employed in clinical practice. The ultimate goal is to establish a standard of care for diaphragmatic dysfunction.

The role of estrogen G-protein coupled receptor 30 (GPR30) and sexual experience in sexual incentive motivation in male rats.

Male rats exhibit reductions in sexual motivation following systemic administration of drugs that inhibit the conversion of testosterone to estrogen, which indicates that estrogen signaling plays a role in male rat sexual motivation. Given that estrogen G-protein coupled receptor 30 (GPR30) is expressed in brain areas that are important for male sexual behaviors and endocrine function, the primary aim of the current study was to examine the role that GPR30 plays in sexual motivation in both sexually naïve and sexually experienced male rats. Following the final treatment with either a GPR30 antagonist (G-15) or vehicle control, male rats were placed into the center chamber of a larger three-chambered testing arena that was designed to assess sexual incentive motivation. A sexually receptive stimulus female rat and a stimulus male rat were individually confined to one of the two smaller chambers that were each separated by a perforated partition from the larger end chambers, which test rats had access to. Relative to vehicle treated rats, male rats treated with G-15 exhibited a reduction in the percentage of time spent in the vicinity of a sexually receptive female rat. Although G-15 reduced sexual incentive motivation independent of sexual experience, only sexually-naïve rats treated with G-15 did not exhibit a preference for the sexually receptive stimulus female rat. Collectively, these results indicate that interference with estrogen signaling at GPR30 reduces sexual motivation and that the lack of preference for a sexually receptive female rat over a male rat following G-15 treatment is abrogated by previous sexual experience.

Comportamiento de las células nucleadas en los distintos tipos de derrame pleural / Behaviour of nucleated cells in various types of pleural effusion

Introducción. El conocimiento del comportamiento de los componentes celulares del líquido pleural puede ayudar a enfocar el diagnóstico diferencial de un derrame pleural. El objetivo es evaluar su composición en los distintos tipos de derrames y valorar si proporciona información clínica relevante. Pacientes y métodos. Estudio observacional, transversal y retrospectivo en el que se analiza el componente celular de derrames pleurales de diversa etiología. Los derrames se clasificaron como neutrofílicos, linfocíticos (≥50% de cada uno de ellos), eosinofílicos (≥10%) o mesoteliales (>5%) y se agruparon en 6 categorías diagnósticas. Resultados. Se estudiaron 1.467 pacientes (354 insuficiencia cardiaca; 59 otros trasudados; 349 paraneumónicos; 133 tuberculosos; 397 neoplásicos y 175 otros exudados). El predominio celular fue linfocítico en la insuficiencia cardiaca (44,4%), paraneumónicos no complicados (29,2%), tuberculosis (88%) y neoplasias (49,6%); neutrofílico en los paraneumónicos (57%) y neoplásicos (9,6%); eosinofílico en las neoplasias (6,3%) y mesotelial en las tuberculosis (12%). Las etiologías más frecuentes con un recuento linfocitario ≥80% fueron tuberculosis (35,1%) y neoplasias (23,3%). Los parámetros con mayor capacidad discriminante fueron: leucocitos (trasudados: AUC 0,835) y porcentaje de neutrófilos (empiemas: AUC 0,906 y paraneumónicos complicados + empiemas: AUC 0,907). Conclusiones. Los recuentos de células nucleadas ayudan a enfocar la etiología del derrame pleural, ya que cada etiología suele tener un predominio celular característico. El porcentaje de células nucleadas en el líquido pleural no puede descartar tuberculosis si existe un recuento elevado de células mesoteliales, ni un derrame paraneumónico ante un predominio linfocítico, o malignidad con un recuento de linfocitos ≥80% (AU)

Introduction. To know the behavior of cellular components of pleural fluid can help focus the differential diagnosis of a pleural effusion. Our objective was to assess their composition in different types of pleural effusions and assess whether it provides relevant clinical information. Patients and methods. Observational, cross-sectional and retrospective study in which the cellular components of pleural effusions of different etiology were analyzed. Pleural effusions were classified as neutrophilic, lymphocytic (≥50% of each one of them), eosinophilic (≥10%) or mesothelial (>5%) and were grouped into six diagnostic categories. Results. 1.467 patients were studied (354 heart failure; 59 other transudates; 349 paraneumonic; 133 tuberculous; 397 malignant and 175 other exudates). The predominance cell was lymphocytic in heart failure (44,4%), uncomplicated parapneumonic (29,2%), tuberculosis (88%) and malignant (49,6%); neutrophilic in parapneumonic (57%) and malignant (9,6%); eosinophilic in malignant (6,3%) and mesotelial in tuberculosis (12%). The most frequent etiologies with lymphocyte count ≥80% were tuberculosis (35,1%) and malignant (23,3%). Parameters with higher discriminating accuracy were: leukocytes (transudates: AUC 0,835) and percentage of neutrophils (empyemas: AUC 0,906 and complicated parapneumonic+empyemas: AUC 0,907). Conclusions. Nucleated cell counts will help focus the etiology of pleural effusions, since each etiology often have a characteristic cell predominance. The percentage of nucleated cells in pleural fluid not ruled out tuberculosis if there is a high count of mesothelial cells, nor a parapneumonic effusion with lymphocytic predominance, or malignancy with ≥80% lymphocytes (AU)

Behaviour of nucleated cells in various types of pleural effusion. / Comportamiento de las células nucleadas en los distintos tipos de derrame pleural.

INTRODUCTION: To know the behavior of cellular components of pleural fluid can help focus the differential diagnosis of a pleural effusion. Our objective was to assess their composition in different types of pleural effusions and assess whether it provides relevant clinical information. PATIENTS AND METHODS: Observational, cross-sectional and retrospective study in which the cellular components of pleural effusions of different etiology were analyzed. Pleural effusions were classified as neutrophilic, lymphocytic (≥50% of each one of them), eosinophilic (≥10%) or mesothelial (>5%) and were grouped into six diagnostic categories RESULTS: 1.467 patients were studied (354 heart failure; 59 other transudates; 349 paraneumonic; 133 tuberculous; 397 malignant and 175 other exudates). The predominance cell was lymphocytic in heart failure (44,4%), uncomplicated parapneumonic (29,2%), tuberculosis (88%) and malignant (49,6%); neutrophilic in parapneumonic (57%) and malignant (9,6%); eosinophilic in malignant (6,3%) and mesotelial in tuberculosis (12%). The most frequent etiologies with lymphocyte count ≥80% were tuberculosis (35,1%) and malignant (23,3%). Parameters with higher discriminating accuracy were: leukocytes (transudates: AUC 0,835) and percentage of neutrophils (empyemas: AUC 0,906 and complicated parapneumonic+empyemas: AUC 0,907). CONCLUSIONS: Nucleated cell counts will help focus the etiology of pleural effusions, since each etiology often have a characteristic cell predominance. The percentage of nucleated cells in pleural fluid not ruled out tuberculosis if there is a high count of mesothelial cells, nor a parapneumonic effusion with lymphocytic predominance, or malignancy with ≥80% lymphocytes.

Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model.

BACKGROUND: OM-85 is an immunostimulant bacterial lysate, which has been proven effective in reducing the number of lower airways infections. We investigated the efficacy of the bacterial lysate OM-85 in the primary prevention of a murine model of asthma. METHODS: In the first phase of our study the animals received doses of 0.5µg, 5µg and 50µg of OM-85 through gavage for five days (days -10 to -6 of the protocol), 10 days prior to starting the sensitisation with ovalbumin (OVA), in order to evaluate the results of dose-response protocols. A single dose (5µg) was then chosen in order to verify in detail the effect of OM-85 on the pulmonary allergic response. Total/differential cells count and cytokine levels (IL-4, IL-5, IL-13 and IFN-γ) from bronchoalveolar lavage fluid (BALF), OVA-specific IgE levels from serum, lung function and lung histopathological analysis were evaluated. RESULTS: OM-85 did not reduce pulmonary eosinophilic response, regardless of the dose used. In the phase protocol using 5µg/animal of OM-85, no difference was shown among the groups studied, including total cell and eosinophil counts in BALF, serum OVA-specific IgE, lung histopathologic findings and lung resistance. However, OM-85 decreased IL-5 and IL-13 levels in BALF. CONCLUSIONS: OM-85, administered in early life in mice in human-equivalent doses, does not inhibit the development of allergic pulmonary response in mice.

Natural killer cells in acute myeloid leukemia patients: from phenotype to transcriptomic analysis.

Chemotherapies allow complete remission in more than 50 % of patients with acute myeloid leukemia (AML), however, with frequent relapse. This suggests that residual leukemic cells may escape to chemotherapy and immune system. Natural killer (NK) cells from AML patients (AML-NK) have a weaker natural cytotoxicity-activating receptors (NCRs) expression than NK cells from healthy donors (HD-NK). Coding genes for NCR1/NKp46, NCR2/NKp44 and NCR3/NKp30 are located at different loci on two different chromosomes; however, their expression is tightly coordinated. Most NK cells express either high (NCRbright) or low levels (NCRdull) of all three NCRs. This suggests the existence of negative/positive regulation factor(s) common to the three receptors. In order to find transcription factor(s) or pathway(s) involved in NCRs co-regulation, this study compared the transcriptomic signature of HD-NK and AML-NK cells, before and after in vitro NK cells culture. Microarrays analysis revealed a specific NK cells transcriptomic signature in patients with AML. However, in vitro NK cells expansion erased this signature and up-regulated expression of central molecules of NK functions, such as NCR, NKG2D and also ETS-1, regardless of their origin, i.e., AML-NK vs HD-NK. ETS-1 transcription factor was shown to bind to a specific and common region in the NCRs promoters, thus appearing as a good candidate to explain the coordinated regulation of three NCRs. Such results are encouraging regarding in vitro AML-NK cytotoxicity restoration and provide a new conceptual support for innovative cellular therapy based on in vitro NK cells expansion before their reinfusion in AML patients.

First 1500 Kidney Transplants at the Institute of Nephrology and Urology in Uruguay: Analysis of the Results.

BACKGROUND: The Institute of Nephrology and Urology (INU) has performed 75% of kidney transplantations (KT) in Uruguay during its 35 years of activity, with 90.6% from cadaveric donors. We investigated the risk factors (RF) for delayed graft function (DGF) and patient and graft survival (SV). METHODS: We analyzed retrospectively the characteristics and evolution of 1500 KT performed by INU until December 2014. The incidence of DGF and RF for patient and graft SV were analyzed in 4 eras, according to the year that KT was performed. RESULTS: The number of KT per year has progressively increased until reaching 40 KT per million population in 2006, with a decrease of the living donor KT (LDKT) rate. The age of the donors (D) and recipients (R) as well as the time on dialysis (TOD) have progressively increased over the different eras. Five hundred twenty-five R (35%) presented with DGF. The RF for DGF were the age of the R and the D, the TOD, the DDKT, and the warm ischemia time (WIT). In the DDKT group, the cold ischemia time and "died of stroke" were added factors. The death-censored graft SV at 1, 5, 10, and 15 years were 90%, 76%, 62%, and 49%, respectively. They improved as from era I, the patient SV being 92%, 83%, and 75% at 1, 5, and 10 years, in era I; 98%, 93%, and 86% in era II; 98%, 92%, and 83% in era III; and 95% and 90% at 1 and 5 years in era IV (P < .001). The graft SV over the same periods was 76%, 58%, and 40% in era I; 88%, 68%, and 52% in era II; 93%, 81%, and 70% in era III; and 93% and 85% at 1 and 5 years in era IV (P < .0001). The RF for patient SV were diabetes mellitus, era I, lower albuminemia, older age or TOD, and DGF. For kidney SV, the era, the age of the R, TOD, DGF, and D older than 60 years were RF associated with a worse evolution. In DDKT, the RF for the graft SV were the era, younger age of the R, and DGF. The group with the worst graft SV was the one made up of children and adolescents. CONCLUSIONS: Our results relating to patient and graft SV are acceptable and comparable to those mentioned on large records such as the OPNT/SRTR and the Collaborative Transplant Study. This has been the case, even though we have transplanted increasingly aged patients, with increasingly aged donors, or donors with associated pathology. The risk factors that we found both for DGF and SV have also been pointed out by other authors. The validity of some findings has the limitation of being from a retrospective analysis; hence, they should be corroborated by a prospective study.

Preemptive kidney transplantation--a team experience in Uruguay.

Kidney transplantation is the best treatment for end-stage chronic renal disease. In Uruguay, the prevalence of patients on dialysis is 757 patients per millon inhabitants, plus 316 alive with a functioning renal graft. We install a preemptive renal transplantation program. Twenty-five patients received grafts without dialysis from 2004 to 2013, 5 receiving their 2nd transplantation and 17 from cadaveric donors, with 7.4 ± 7.7 months in the waiting list. At 24 months, patients' survival rate was 100% and the grafts' 97%, with a serum creatinine of 1.4 ± 0.6 mg%. The developed programs of dialysis and renal health care contributed install our preemptive kidney transplantation. Kidney transplantation should be proposed to selected patients with chronic renal failure as primary therapy of substitution of renal function.

Descriptive retrospective comparative study between two brands of mycophenolate mofetil used in Uruguay: innovator versus generic (Suprimun).

BACKGROUND: According to our experience, survival of cadaveric renal graft in 5 years increased from 63% as of the introduction of cyclosporine to 73% after azathioprine was substituted with mycophenolate mofetil (MMF) in 1997. Until 2003, the innovator mycophenolate mofetil (IMMF) (Cellcept; Roche) was used. In 2003, Laboratorios Clausen introduced in Uruguay a generic MMF (GMMF) (Suprimun/Micoflavin/Myclausen; Laboratorios Clausen) with previous bioequivalence studies. Since then, every health care provider administers one of these types of MMF available on the market to its renal transplant (RT) patients. METHODS: We compared the evolution of 2 groups of patients and their grafts, those treated with GMMF or with IMMF. This was a descriptive, retrospective, nonrandomized, comparative study that involved all transplant patients in a center from January 2005 to June 2010 from 2 different health care providers which administered GMMF or IMMF uninterruptedly. Patients were older than 18 years, underwent their first RT and received triple immunosuppressive regime with calcineurin inhibitor (CNI), corticoids, and MMF, and completed ≥6 months of post-RT evolution. RESULTS: The GMMF group included 29 patients and the IMMF group 23. Patients from both groups had no significant differences (NS) regarding age, sex, diabetes, hepatitis C virus (HCV), recipient hypertension, donor type (living or cadaveric, sex, age, cause of death), or mismatch degree. There were no material differences regarding antibody induction, CNI type, day of diuresis, or function recovery percentage. Statistically different results were reported for time in dialysis (6.1 ± 0.7 y in IMMF vs 3.8 ± 0.5 y in GMMF) and cadaveric donor cold ischemia time (989 ± 205 min vs 851 ± 219 min, respectively). For IMMF and GMMF, respectively, clinical acute rejection was 40.9% and 31% and creatinine over 3, 6, 12, 24, 36, and 48 months, respectively, was (mg%): 1.65 ± 0.12, 1.66 ± 0.15, 1.43 ± 0.10, 1.44 ± 0.12, 1.49 ± 0.18, and 1.41 ± 0.17 and 1.50 ± 0.08, 1.41 ± 0.07, 1.63 ± 0.26, 1.31 ± 0.08, 1.26 ± 0.09, and 1.21 ± 0.10, with 22/28, 22/28, 22/28, 22/26, 19/20, 17/11, and 15/9 patients under follow-up (NS). Patient survival over 3, 6, 12, and 18 months, respectively, was 94%, 94%, 94%, and 94% and 96%, 96%, 96%, and 96%, and graft survival was 94%, 89%, 89%, and 89% and 96%, 93%, 93%, and 93% for IMMF and GMMF, respectively (NS). Dosing adjustment frequency and substitution with mycophenolate sodium was similar for both groups. CONCLUSIONS: With the results of this preliminary study we can not reach any final conclusion regarding assistance practice. From both groups, which involved similar baseline variables except for time in dialysis and cold ischemia (both greater in IMMF), we could gather a similar graft and patient evolution. New prospective, randomized, double-blind studies involving an adequate number of patients will help to determine the efficacy of GMMF in renal transplantation.

Extracellular DNA traps in bronchoalveolar fluid from a murine eosinophilic pulmonary response.

Asthma is associated with a loss of the structural integrity of airway epithelium and dysfunction of the physical barrier, which protects airways from external harmful factors. Granulocyte activation causes the formation of extracellular traps, releasing web-like structures of DNA and proteins, being important to kill pathogens extracellularly. We investigated whether eosinophils infiltrating airways in an experimental model of asthma would induce eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid and lung tissue. We showed that an ovalbumin (OVA) asthma protocol presented a significant increase in eosinophil counts with increased extracellular DNA in bronchoalveolar lavage fluid as well as in lung tissue, confirming the presence of DNA traps colocalized with eosinophil peroxidase. EETs formation was reversed by DNase treatment. With these approaches, we demonstrated for the first time that OVA-challenged mice release extracellular DNA traps, which could aggravate pulmonary dysfunction.