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2.
Pathobiology ; 91(2): 132-143, 2024.
Article in English | MEDLINE | ID: mdl-37797584

ABSTRACT

INTRODUCTION: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. MATERIALS AND METHODS: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. RESULTS: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. CONCLUSIONS: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).


Subject(s)
Melanoma , Skin Neoplasms , Animals , Mice , Humans , Ki-67 Antigen , Retrospective Studies , Heterografts , Epithelial-Mesenchymal Transition , Mice, Inbred NOD , Mice, SCID , Cell Line, Tumor , Cadherins , Biomarkers, Tumor/metabolism
3.
Lupus ; 33(1): 83-87, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38018810

ABSTRACT

Lymphoid interstitial pneumonia (LIP) is a rare form of interstitial pulmonary disease, which has been described in association with a wide range of autoimmune disorders. Although the association of this entity with Sjogren's syndrome is well known, only a few cases are reported in relation to systemic lupus erythematosus (SLE). The aim of this paper is to review the cases reported in literature to date, as well as to describe the characteristics of these patients including the new case presented herein. We will be focusing on the case of a 36-year-old female patient diagnosed with SLE on hydroxychloroquine treatment who develops pleuritic chest pain and progressive dyspnea after 3 years of follow-up. The chest CT scan showed pleural thickening and both multiple and bilateral micronodules. A lung biopsy was also performed, revealing an infiltration of lymphocytes, plasma cells, and histiocytes in the alveolar septa suggestive of LIP. After conducting a review of the literature, we identified seven other cases describing SLE in association with LIP. The majority of them were young women, and LIP tends to appear early in the course of the disease, even as a form of initial presentation in some cases. Symptoms included cough, dyspnea, and pleuritic pain, with the exception of one case which was asymptomatic. It is noteworthy that half of the patients were positive for anti-SSA/anti-SSB autoantibodies, and some of them also met criteria for Sjogren's syndrome. Treatment with steroids and other immunosuppressive agents improved symptoms in all of them.


Subject(s)
Lung Diseases, Interstitial , Lupus Erythematosus, Systemic , Pleurisy , Sjogren's Syndrome , Humans , Female , Adult , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/drug therapy , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Pleurisy/complications , Dyspnea/etiology
4.
Am J Case Rep ; 24: e939726, 2023 Jun 17.
Article in English | MEDLINE | ID: mdl-37329130

ABSTRACT

BACKGROUND The incidence of glomerular disease recurrence in kidney transplant patients varies according to type of glomerulopathy; therefore, it is important to know the primary chronic kidney disease etiology. C3 glomerulopathy (C3G) is characterized by deposits of C3 in immunofluorescence and its pathogeny is based on the dysregulation of the alternative complement pathway. C3G has a high recurrence rate and, given its low prevalence, only case series have been published. A higher rate of recurrence and a more aggressive course have been described in association with monoclonal gammopathy (MG). CASE REPORT We describe the case of a 78-year-old man with chronic kidney disease of unknown etiology (no significant proteinuria) and monoclonal IgGl gammopathy with low risk of progression, who received a kidney transplant, presenting accelerated deterioration of kidney function. Histopathology showed predominant C3 deposits in immunofluorescence, compatible with C3 glomerulonephritis (C3GN). He was treated with eculizumab during 4 weeks while the study was completed. The response to treatment was not favorable and the patient remained in the dialysis program. CONCLUSIONS Further studies are needed to explain the pathogenic mechanisms of complement alternative pathway dysregulation mediated by monoclonal component in patients with C3GN and MG. Patients older than 50 years who are on a waiting list for kidney transplantation should have an MG detection study. The information provided to patients with MG on a waiting list for kidney transplantation should include not only the possibility of hematologic progression but also the recurrence/de novo appearance of associated kidney pathology.


Subject(s)
Glomerulonephritis, Membranoproliferative , Glomerulonephritis , Monoclonal Gammopathy of Undetermined Significance , Paraproteinemias , Renal Insufficiency, Chronic , Male , Humans , Aged , Complement C3/metabolism , Renal Dialysis , Glomerulonephritis/etiology , Glomerulonephritis/diagnosis , Renal Insufficiency, Chronic/etiology , Glomerulonephritis, Membranoproliferative/etiology
5.
ASAIO J ; 69(3): 324-331, 2023 03 01.
Article in English | MEDLINE | ID: mdl-35609139

ABSTRACT

Particulate and gaseous microemboli (GME) are side effects of cardiac surgery that interfere with postoperative recovery by causing endothelial dysfunction and vascular blockages. GME sources during surgery are multiple, and cardiopulmonary bypass (CPB) is contributory to this embolic load. Hematic antegrade repriming (HAR) is a novel procedure that combines the benefits of repriming techniques with additional measures, by following a standardized procedure to provide a reproducible hemodilution of 300 ml. To clarify the safety of HAR in terms of embolic load delivery, a prospective and controlled study was conducted, by applying Doppler probes to the extracorporeal circuit, to determine the number and volume of GME released during CPB. A sample of 115 patients (n = 115) was considered for assessment. Both groups were managed under strict normothermia, and similar clinical conditions and protocols, receiving the same open and minimized circuit. Significant differences in GME volume delivery (control group [CG] = 0.28 ml vs. HAR = 0.08 ml; p = 0.004) and high embolic volume exposure (>1 ml) were found between the groups (CG = 30.36% vs. HAR = 4.26%; p = 0.001). The application of HAR did not represent an additional embolic risk and provided a four-fold reduction in the embolic volume delivered to the patient (coefficient, 0.24; 95% CI, 0.08-0.72; p = 0.01), which appears to enhance GME clearance of the oxygenator before CPB initiation.


Subject(s)
Cardiopulmonary Bypass , Embolism, Air , Humans , Cardiopulmonary Bypass/adverse effects , Cardiopulmonary Bypass/methods , Embolism, Air/etiology , Embolism, Air/prevention & control , Prospective Studies , Equipment Design , Oxygenators/adverse effects
6.
Transplant Proc ; 52(2): 512-514, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32059940

ABSTRACT

Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection in renal transplantation. It is characterized by the presence of mature plasma cells that compromise more than 10% of inflammatory cells infiltrating the renal graft. The pathogenesis of PCAR is unknown, appears late, and has been related mainly to insufficient immunosuppression or infections. The treatment is not clearly defined, and the graft survival is poor. Here, we report a case series of 3 Spanish patients diagnosed with PCAR accompanied by donor-specific antibodies (DSA) after kidney transplantation. Mean to diagnosis was 2-12 years post-transplantation, and they began with abrupt deterioration of renal function. All patients were women and had preceding viral infection. In addition, two of the three patients recognize a doubtful adherence to immunosuppression. About treatment, 2 of the 3 patients, because the biopsy of the renal graft showed signs suggestive of incipient antibody-mediated rejection (ABMR) (glomerulitis, capilaritis, transplant glomerulopathy), were started with corticosteroids, anti-thymoglobulin, plasmapheresis, and intravenous immunoglobulins. The last patient, who only showed PCAR at biopsy, was treated with corticosteroids and anti-thymoglobulin. After treatment, graft function improved in all of them, but one patient developed an ABMR and another required a dialysis program, all of which indicates the difficulty in management and treatment of PCAR.


Subject(s)
Graft Rejection/immunology , Kidney Transplantation/adverse effects , Plasma Cells/immunology , Postoperative Complications/immunology , Adult , Antibodies/blood , Antibodies/immunology , Biopsy , Female , Graft Rejection/blood , Humans , Kidney/immunology , Kidney/pathology , Postoperative Complications/blood , Tissue Donors , Transplants/immunology , Transplants/pathology
8.
Ups J Med Sci ; 125(1): 19-29, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31809668

ABSTRACT

Background: An antibody panel is needed to definitively differentiate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in order to meet more stringent requirements for the histologic classification of lung cancers. Staining of desmosomal plaque-related proteins may be useful in the diagnosis of lung SCC.Materials and methods: We compared the usefulness of six conventional (CK5/6, p40, p63, CK7, TTF1, and Napsin A) and three novel (PKP1, KRT15, and DSG3) markers to distinguish between lung SCC and AC in 85 small biopsy specimens (41 ACs and 44 SCCs). Correlations were examined between expression of the markers and patients' histologic and clinical data.Results: The specificity for SCC of membrane staining for PKP1, KRT15, and DSG3 was 97.4%, 94.6%, and 100%, respectively, and it was 100% when the markers were used together and in combination with the conventional markers (AUCs of 0.7619 for Panel 1 SCC, 0.7375 for Panel 2 SCC, 0.8552 for Panel 1 AC, and 0.8088 for Panel 2 AC). In a stepwise multivariate logistic regression model, the combination of CK5/6, p63, and PKP1 in membrane was the optimal panel to differentiate between SCC and AC, with a percentage correct classification of 96.2% overall (94.6% of ACs and 97.6% of SCCs). PKP1 and DSG3 are related to the prognosis.Conclusions: PKP1, KRT15, and DSG3 are highly specific for SCC, but they were more useful to differentiate between SCC and AC when used together and in combination with conventional markers. PKP1 and DSG3 expressions may have prognostic value.


Subject(s)
Adenocarcinoma/diagnosis , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/diagnosis , Desmosomes/metabolism , Lung Neoplasms/diagnosis , Adenocarcinoma/metabolism , Carcinoma, Squamous Cell/metabolism , Desmoglein 3/metabolism , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Keratin-15/metabolism , Lung Neoplasms/metabolism , Male , Middle Aged , Plakophilins/metabolism , Prognosis , Sensitivity and Specificity
10.
Eur Heart J Cardiovasc Imaging ; 21(4): 378-386, 2020 04 01.
Article in English | MEDLINE | ID: mdl-31702781

ABSTRACT

AIMS: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a life-threatening entity with a highly heterogeneous genetic background. Cardiac magnetic resonance (CMR) imaging can identify fibrofatty scar by late gadolinium enhancement (LGE). Our aim is to investigate genotype-phenotype correlation in ARVC/D mutation carriers, focusing on CMR-LGE and myocardial fibrosis patterns. METHODS AND RESULTS: A cohort of 44 genotyped patients, 33 with definite and 11 with borderline ARVC/D diagnosis, was characterized using CMR and divided into groups according to their genetic condition (desmosomal, non-desmosomal mutation, or negative). We collected information on cardiac volumes and function, as well as LGE pattern and extension. In addition, available ventricular myocardium samples from patients with pathogenic gene mutations were histopathologically analysed. Half of the patients were women, with a mean age of 41.6 ± 17.5 years. Next-generation sequencing identified a potential pathogenic mutation in 71.4% of the probands. The phenotype varied according to genetic status, with non-desmosomal male patients showing lower left ventricular (LV) systolic function. LV fibrosis was similar between groups, but distribution in non-desmosomal patients was frequently located at the posterolateral LV wall; a characteristic LV subepicardial circumferential LGE pattern was significantly associated with ARVC/D caused by desmin mutation. Histological analysis showed increased fibrillar connective tissue and intercellular space in all the samples. CONCLUSION: Desmosomal and non-desmosomal mutation carriers showed different morphofunctional features but similar LV LGE presence. DES mutation carriers can be identified by a specific and extensive LV subepicardial circumferential LGE pattern. Further studies should investigate the specificity of LGE in ARVC/D.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia , Cardiomyopathies , Adult , Arrhythmogenic Right Ventricular Dysplasia/diagnostic imaging , Arrhythmogenic Right Ventricular Dysplasia/genetics , Arrhythmogenic Right Ventricular Dysplasia/pathology , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/genetics , Cardiomyopathies/pathology , Contrast Media , Female , Fibrosis , Gadolinium , Genetic Association Studies , Humans , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Mutation , Myocardium/pathology , Young Adult
11.
Metas enferm ; 22(10): 14-20, dic. 2019. tab
Article in Spanish | IBECS | ID: ibc-185327

ABSTRACT

Objetivo: describir la calidad del desayuno de los niños y las niñas de 4 a 9 años de un municipio de Madrid, y de sus cuidadores familiares. Método: se diseñó un estudio descriptivo transversal en el Centro de Salud Alicante en Fuenlabrada (Madrid) con la población infantil de entre 4 y 9 años, que acudían a consulta de Enfermería para revisiones programadas junto al familiar/tutor con quien realizaban habitualmente el desayuno. Los datos se recogieron mediante entrevista clínica y exploración antropométrica en consulta, empleándose el cuestionario "Test de desayuno saludable" de la Comunidad de Madrid para obtener los datos de la calidad del desayuno. Se llevó a cabo un análisis descriptivo, usando media y desviación estándar (DE) para las variables cuantitativas y frecuencias para las cualitativas. Resultados: participaron 289 niños/as, con una edad media (DE) de 5,83 (1,98) años. 240 niños (83,1%) presentaban normopeso, 29 (10%) sobrepeso y 20 (6,9%) obesidad. La calidad global del desayuno fue adecuada en el 38,7% de los casos mientras que el 61,3% restante necesitaba mejorar o replantearse el desayuno por no alcanzar el mínimo requerido. El 25,6% de los cuidadores hacía un desayuno de calidad, mientras que el 74,4% necesitaba mejorar o replantearse sus hábitos dietéticos en el desayuno. Conclusiones: un desayuno nutricionalmente adecuado se asocia con un mejor rendimiento físico e intelectual y mejor estado de salud, incluyendo la prevención de la obesidad. En el presente estudio los datos para un desayuno de calidad revelan que más de la mitad de los niños/as de 4-9 años de edad necesitan mejorar o replantearse el desayuno


Objective: to describe the quality of breakfast in 4-to-9-year old boys and girls and their family caregivers in a Madrid district. Method: a descriptive cross-sectional study was designed at the Centro de Salud Alicante in Fuenlabrada (Madrid) with the pediatric population between 4 and 9-year-old who attended the Nursing Unit for scheduled routine examinations with the relative/tutor with whom they had breakfast usually. Data were collected through clinical interview and anthropometric examination during the visit; the "Healthy Breakfast Test" of the Community of Madrid was used to obtain data about the quality of breakfast. A descriptive analysis was conducted, using mean and standard deviation (SD) for the quantitative variables, and frequencies for qualitative variables. Results: the study included 289 boys and girls, with a mean age (SD) of 5.83 (1.98) years; 240 children (83.1%) presented normal weight, 29 (10%) overweight and 20 (6.9%) obesity. The overall quality of breakfast was adequate in 38.7% of cases, while the remaining 61.3% needed to improve or reconsider breakfast because they did not reach the minimum required. Of caregivers, 25.6% had a quality breakfast, while 74.4% needed to improve or reconsider their diet habits at breakfast. Conclusions: a nutritionally adequate breakfast is associated with better physical and intellectual performance and better health status, including the prevention of obesity. In the present study, quality breakfast data revealed that over half of 4-to-9-year-old children needed to improve or reconsider their breakfast


Subject(s)
Humans , Male , Female , Child , Child, Preschool , Breakfast , Office Nursing , Infant Nutrition , School Feeding , Anthropometry , Surveys and Questionnaires , Qualitative Research , Caregivers , Pediatric Obesity/diet therapy , School Nursing
14.
Biomédica (Bogotá) ; 38(4): 456-462, oct.-dic. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-983954

ABSTRACT

El síndrome hemofagocítico es una condición clínica e histológica grave, secundaria a diferentes procesos. La glomerulonefritis colapsante es una podocitopatía proliferativa, generalmente de pronóstico desfavorable para la función renal. Se presenta un caso en el que las dos condiciones aparecieron asociadas, lo cual es una forma infrecuente de presentación del linfoma hepatoesplénico de células T. Se discute, asimismo, el papel de los marcadores de desdiferenciación podocitaria en esta glomerulopatía, y se revisan la fisiopatología y el tratamiento.


The hemophagocytic syndrome is a serious clinical-histological entity secondary to different diseases. Collapsing glomerulonephritis is a proliferative podocytopathy that usually has an unfavorable renal prognosis. We present a case in which both entities were associated, which is an infrequent form of hepatosplenic T-cell lymphoma. In addition, we review the role of the markers of podocyte dedifferentiation in this glomerulopathy and its pathophysiology and treatment.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Glomerulonephritis , Antigens, Differentiation , Renal Insufficiency , Lymphoma , Lymphoproliferative Disorders
15.
Sci Rep ; 8(1): 15203, 2018 10 12.
Article in English | MEDLINE | ID: mdl-30315279

ABSTRACT

Obesity-related comorbidities are, in large part, originated from the dysfunction of adipose tissue. Most of them revert after the normalization of body mass. Adipose tissue is essentially occupied by adipocytes. However, different populations of immunological cells and adipocyte precursor cells (AdPCs) are the main cellular components of tissue. During obesity, body fat depots acquire a low-level chronic inflammation and adipocytes increase in number and volume. Conversely, weight loss improves the inflammatory phenotype of adipose tissue immune cells and reduces the volume of adipocytes. Nevertheless, very little is known about the evolution of the human AdPCs reservoir. We have developed a flow cytometry-based methodology to simultaneously quantify the main cell populations of adipose tissue. Starting from this technical approach, we have studied human adipose tissue samples (visceral and subcutaneous) obtained at two different physiological situations: at morbid obesity and after bariatric surgery-induced weight loss. We report a considerable increase of the AdPCs reservoir after losing weight and several changes in the immune cells populations of adipose tissue (mast cells increase, neutrophils decrease and macrophages switch phenotype). No changes were observed for T-lymphocytes, which are discussed in the context of recent findings.


Subject(s)
Adipocytes/cytology , Adipose Tissue/cytology , Bariatric Surgery , Flow Cytometry/methods , Stem Cells/cytology , Weight Loss/physiology , Adult , Cell Count , Cell Size , Cohort Studies , Endothelial Cells/metabolism , Female , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Stromal Cells/cytology
16.
Nefrología (Madrid) ; 38(3): 297-303, mayo-jun. 2018. tab, graf
Article in Spanish | IBECS | ID: ibc-177496

ABSTRACT

INTRODUCCIÓN: El KDRI y su variante KDPI son dos herramientas utilizadas para la valoración del donante renal. Se ha propuesto la utilidad del KDPI como sustituto/complementario a la biopsia renal preimplantación. Estos scores no están validados en España. OBJETIVO: 1) Investigar la concordancia entre los scores KDPI e histológico (biopsia renal preimplantación), y 2) valorar la relación entre el KDRI, KDPI y la puntuación histológica sobre la supervivencia del injerto, en donantes con criterios expandidos (ECD). METODOLOGÍA: Estudio de cohortes, unicéntrico, retrospectivo desde el 1 de enero de 1998 hasta el 31 de diciembre de 2010. RESULTADOS: Se reclutaron 120 donantes y 220 biopsias preimplantación. Ciento cuarenta y cuatro (65,5%) injertos fueron aptos para trasplante. Setenta y seis (34,5%) fueron descartados. Tiempo medio de seguimiento 6,4 años (ds 3,9). Edad media de los donantes 63,1 años (ds 8,2), varones (145; 65,9%), no diabéticos (191; 86,8%) y sin otros factores de riesgo cardiovascular (173; 78,6%). Causa de muerte mayoritaria ACV hemorrágico (153; 69,5%). La puntuación KDPI media entre los grupos riñón válido (1,56/89; ds 0,22) y no válido (1,66/93; ds 0,15) es estadísticamente significativa (p < 0,01). El KDPI mostró una concordancia y correlación moderadas con el score histológico (AUC 0,64/coeficiente de correlación 0,24, p < 0,01). Los scores KDPI (HR 24,3, p < 0,01) y KDRI (HR 23,3, p < 0,01) están relacionados con la supervivencia del injerto en el análisis multivariante. CONCLUSIÓN: 1) Los scores KDPI e histológico presentan una concordancia moderada. 2) Las puntuaciones KDPI, y sobre todo KDRI, son válidas para estimar la supervivencia de los injertos y pueden ser utilizadas de forma combinada con la biopsia para la toma de decisiones individualizadas en el grupo de donantes con criterios expandidos


INTRODUCTION: KDRI / KDPI are tools use in kidney donor evaluation. It has been proposed as a substitute of, or complementary to preimplantation renal biopsy. These scores has not been validated in Spain. OBJECTIVE: 1) To investigate the concordance between KDPI and histological scores (preimplantation renal biopsy) and 2) To assess the relationship between KDRI, KDPI and histological score on graft survival in the expanded criteria donors group. METHODOLOGY: Retrospective cohort study from 1 January 1998 until 31 December 2010. RESULTS: During the study 120 donors were recruited, that resulted in 220 preimplantation renal biopsies. 144 (65%) grafts were considered suitable for kidney transplantation. 76 (34.5%) were discarded. Median follow up has been 6.4 years (sd 3.9). Median age 63.1 years (sd 8.2), males (145; 65.9%), non-diabetic (191; 86.8%) and without another cardiovascular risk factors (173; 78.6%). 153 (69.5%) donors died of cerebrovascular disease. There were significant differences in KDRI/KDPI score in both groups 1.56/89 (sd 0.22) vs 1.66/93 (sd 0.15), p < 0.01). The KDPI showed moderate concordance and correlation with the histological score (AUC 0.64 / correlation coefficient 0.24, p <0.01). KDPI (HR 24.3, p < 0.01) and KDRI (HR 23.3, p < 0.01) scores were associated with graft survival in multivariate analysis. CONCLUSION: 1) KPDI and histological scores show moderate concordance. The utility of both scores as combined tools it has to be determined. 2) KDPI score, and especially KDRI score, are valid for estimating graft survival and combined with the biopsy can help to individualized decision making in the expanded criteria donors pool


Subject(s)
Humans , Male , Female , Middle Aged , Donor Selection , Kidney/pathology , Kidney Transplantation , Retrospective Studies , Cohort Studies , Follow-Up Studies , Biopsy
18.
Biosci Rep ; 38(2)2018 04 27.
Article in English | MEDLINE | ID: mdl-29599129

ABSTRACT

The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-ß-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition.


Subject(s)
Acute Kidney Injury , Cisplatin/adverse effects , Isoquinolines/pharmacology , Kidney , Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Animals , Cisplatin/pharmacology , Fibrosis , Kidney/metabolism , Kidney/pathology , Kidney Function Tests , Male , Rats , Rats, Wistar
19.
Eur Heart J Acute Cardiovasc Care ; 7(7): 602-608, 2018 Oct.
Article in English | MEDLINE | ID: mdl-28029052

ABSTRACT

BACKGROUND: Recent advances in the diagnosis and treatment of acute aortic syndrome should improve the outcome of this disease. The Spanish Registry of Acute Aortic Syndrome aimed to assess current results in acute aortic syndrome management in a wide cohort of hospitals in the same geographical area. METHODS: From January 2012 to January 2014, 26 tertiary hospitals included 629 consecutive patients with acute aortic syndrome: 73% men, mean age 64.7±14 years (range 22-92), 443 type A (70.4%) and 186 type B (29.6%). RESULTS: Time elapsed between symptom onset and diagnosis was <12 hours in 70.7% of cases and <24 hours in 84.0% (median 5 hours; 25th-75th percentiles, 2.7-15.5 hours). Computed tomography was the first diagnostic technique in 78% of patients and transthoracic echocardiography in 15%. Surgical treatment was indicated in 78.3% of type A acute aortic syndrome. The interval between diagnosis and surgery was 4.8 hours (quartile 1-3, 2.5-11.4 hours). Among the patients with type B acute aortic syndrome, treatment was medical in 116 cases (62.4%), endovascular in 61 (32.8%) and surgical in nine (4.8%). Type A mortality during hospitalisation was 25.1% in patients treated surgically and 68% in those treated medically. Mortality in type B was 13.8% in those with medical treatment, 18.0% with endovascular therapy and 33.0% with surgical treatment. CONCLUSION: Improvements in the diagnosis and treatment of acute aortic syndrome have not resulted in a significant reduction in hospital mortality. The results of this study reflect more overall and less selected information on acute aortic syndrome management and the need for sustained advances in the therapeutic strategy of acute aortic syndrome.


Subject(s)
Aortic Aneurysm, Thoracic/diagnosis , Aortic Dissection/diagnosis , Endovascular Procedures/methods , Registries , Stents , Acute Disease , Adult , Aged , Aged, 80 and over , Aortic Dissection/mortality , Aortic Dissection/surgery , Aortic Aneurysm, Thoracic/mortality , Aortic Aneurysm, Thoracic/surgery , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Spain/epidemiology , Survival Rate/trends , Syndrome , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
20.
Nefrologia (Engl Ed) ; 38(3): 297-303, 2018.
Article in English, Spanish | MEDLINE | ID: mdl-29132985

ABSTRACT

INTRODUCTION: KDRI / KDPI are tools use in kidney donor evaluation. It has been proposed as a substitute of, or complementary to preimplantation renal biopsy. These scores has not been validated in Spain. OBJECTIVE: 1) To investigate the concordance between KDPI and histological scores (preimplantation renal biopsy) and 2) To assess the relationship between KDRI, KDPI and histological score on graft survival in the expanded criteria donors group. METHODOLOGY: Retrospective cohort study from 1 January 1998 until 31 December 2010. RESULTS: During the study 120 donors were recruited, that resulted in 220 preimplantation renal biopsies. 144 (65%) grafts were considered suitable for kidney transplantation. 76 (34.5%) were discarded. Median follow up has been 6.4 years (sd 3.9). Median age 63.1 years (sd 8.2), males (145; 65.9%), non-diabetic (191; 86.8%) and without another cardiovascular risk factors (173; 78.6%). 153 (69.5%) donors died of cerebrovascular disease. There were significant differences in KDRI/KDPI score in both groups 1.56/89 (sd 0.22) vs 1.66/93 (sd 0.15), p<0.01). The KDPI showed moderate concordance and correlation with the histological score (AUC 0.64 / correlation coefficient 0.24, p <0.01). KDPI (HR 24.3, p<0.01) and KDRI (HR 23.3, p<0.01) scores were associated with graft survival in multivariate analysis. CONCLUSION: 1) KPDI and histological scores show moderate concordance. The utility of both scores as combined tools it has to be determined. 2) KDPI score, and especially KDRI score, are valid for estimating graft survival and combined with the biopsy can help to individualized decision making in the expanded criteria donors pool.


Subject(s)
Donor Selection/methods , Kidney Transplantation , Tissue and Organ Procurement/methods , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment
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