Impaired intratumoral dendritic cell function and potential predictive value of dendritic cell markers for metastasis in malignant salivary gland tumors.

BACKGROUND: The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. MATERIAL AND METHODS: Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen D-related (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. RESULTS: Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA (p=0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p<0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p=0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. CONCLUSIONS: These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies.

Análisis de los resultados y los factores adversos de la reparación artroscópica de las lesiones del subescapular de origen degenerativo / Analysis of the results and adverse factors of arthroscopic repair of degenerative subscapular lesions

Objetivo: Realizar una revisión de roturas del subescapular (SBE) de origen degenerativo tras su reparación por artroscopia y evaluar si los resultados son equiparables en términos de dolor y función a los de pacientes más jóvenes con roturas traumáticas. Material y método: Se han revisado de forma retrospectiva los datos de 80 roturas de SBE de las 660 roturas de manguito rotador intervenidas por el mismo equipo de cirujanos desde junio de 2008 hasta junio de 2018. Se recogieron los datos clínicos de los pacientes intervenidos: edad, género, lateralidad, demora de intervención, patologías asociadas, localización del dolor, valor de la escala visual analógica (EVA) y del test de Constant-Murley (TCM); se han recogido también los datos quirúrgicos: tipo y tamaño de lesión, lesión asociada del bíceps y gesto quirúrgico asociado, estenosis coracoidea y gesto quirúrgico asociado y número y tipo de anclajes empleados. Se realizó estudio estadístico con prueba de regresión lineal múltiple, pruebas paramétricas (t de Student o ANOVA) y pruebas no paramétricas. Resultados: De 80 pacientes, 36 fueron mujeres (45%) y 44, hombres (55%); media de edad de 61años (rango 47 a 81); demora media de la cirugía de 3,5meses (rango 1 a 6); hombro derecho afecto en 46 casos (57,5%), el izquierdo en 34 (42,5%); 22 (27,5%) fueron lesiones aisladas, 58 (72,5%), asociadas a rotura del supraespinoso (SPE). La mejoría media fue de 5,0 puntos en términos de la EVA y de 39,9 puntos de media en el TCM. Índice de nueva rotura, 1,25%. Factores adversos: tamaño de la rotura, demora de intervención, mujeres. Los pacientes con rotura tipo I-B tienen mejor resultado total en el TCM que los tipos I-A y III. A mayor demora se observan peores resultados, tanto de la EVA como del TCM. Las mujeres presentan resultados peores y estadísticamente significativos tanto en la EVA (p=0,00) como en el TCM (p=0,01).(AU)

Objective: To carry out a review of degenerative subscapularis ruptures (SSC) after their arthroscopic repair and to evaluate whether the results are comparable in terms of pain and function to those of younger patients with traumatic ruptures. Methods: The data of 80 SSC tears of the 660 rotator cuff tears operated on by the same team of surgeons from June 2008 to June 2018 were retrospectively reviewed. The clinical data of the surgical indications were collected: age, gender, laterality, intervention delay, associated pathologies, location of pain, value of the Visual Analogue Scale (VAS) and the Constant-Murley test (CMT); surgical data were also collected: type and size of lesion, associated biceps injury and associated surgical procedure, coracoid stenosis and associated surgical procedure, number and type of anchors used. A statistical study was performed with multiple linear regression test, parametric tests (Student's t or ANOVA) and non-parametric tests. Results: Of 80 patients, 36 were women (45%) and 44, men (55%); mean age 61years (range 47 to 81); mean delay of surgery 3.5months (range 1 to 6); right shoulder affected in 46 cases (57.5%), left in 34 (42.5%); 22 (27.5%) were isolated lesions, 58 (72.5%) were associated with supraspinatus rupture (SE). The mean improvement was 5.0 points in terms of the VAS and 39.9 points on average in the CMT. New breakage rate, 1.25%. Adverse factors: size of the tear, delay in intervention, women. Patients with type I-B rupture have a better overall result in the CMT than types I-A and III. The longer the delay, the worse results are observed, both for the VAS and the CMT. Women present worse and statistically significant results both in the VAS (P=.00) and in the CMT (P=.01). Conclusions: Excellent and good results have been obtained in this group of patients, but there are adverse factors such as the size of the tear, the duration of the symptoms and the association of other pathologies, especially in women.(AU)

[Translated article] Analysis of the results and adverse factors of arthroscopic repair of degenerative subscapular lesions / Análisis de los resultados y los factores adversos de la reparación artroscópica de las lesiones del subescapular de origen degenerative

Objetivo: Realizar una revisión de roturas del subescapular (SBE) de origen degenerativo tras su reparación por artroscopia y evaluar si los resultados son equiparables en términos de dolor y función a los de pacientes más jóvenes con roturas traumáticas. Material y método: Se han revisado de forma retrospectiva los datos de 80 roturas de SBE de las 660 roturas de manguito rotador intervenidas por el mismo equipo de cirujanos desde junio de 2008 hasta junio de 2018. Se recogieron los datos clínicos de los pacientes intervenidos: edad, género, lateralidad, demora de intervención, patologías asociadas, localización del dolor, valor de la escala visual analógica (EVA) y del test de Constant-Murley (TCM); se han recogido también los datos quirúrgicos: tipo y tamaño de lesión, lesión asociada del bíceps y gesto quirúrgico asociado, estenosis coracoidea y gesto quirúrgico asociado y número y tipo de anclajes empleados. Se realizó estudio estadístico con prueba de regresión lineal múltiple, pruebas paramétricas (t de Student o ANOVA) y pruebas no paramétricas. Resultados: De 80 pacientes, 36 fueron mujeres (45%) y 44, hombres (55%); media de edad de 61años (rango 47 a 81); demora media de la cirugía de 3,5meses (rango 1 a 6); hombro derecho afecto en 46 casos (57,5%), el izquierdo en 34 (42,5%); 22 (27,5%) fueron lesiones aisladas, 58 (72,5%), asociadas a rotura del supraespinoso (SPE). La mejoría media fue de 5,0 puntos en términos de la EVA y de 39,9 puntos de media en el TCM. Índice de nueva rotura, 1,25%. Factores adversos: tamaño de la rotura, demora de intervención, mujeres. Los pacientes con rotura tipo I-B tienen mejor resultado total en el TCM que los tipos I-A y III. A mayor demora se observan peores resultados, tanto de la EVA como del TCM. Las mujeres presentan resultados peores y estadísticamente significativos tanto en la EVA (p=0,00) como en el TCM (p=0,01).(AU)

Objective: To carry out a review of degenerative subscapularis ruptures (SSC) after their arthroscopic repair and to evaluate whether the results are comparable in terms of pain and function to those of younger patients with traumatic ruptures. Methods: The data of 80 SSC tears of the 660 rotator cuff tears operated on by the same team of surgeons from June 2008 to June 2018 were retrospectively reviewed. The clinical data of the surgical indications were collected: age, gender, laterality, intervention delay, associated pathologies, location of pain, value of the Visual Analogue Scale (VAS) and the Constant-Murley test (CMT); surgical data were also collected: type and size of lesion, associated biceps injury and associated surgical procedure, coracoid stenosis and associated surgical procedure, number and type of anchors used. A statistical study was performed with multiple linear regression test, parametric tests (Student's t or ANOVA) and non-parametric tests. Results: Of 80 patients, 36 were women (45%) and 44, men (55%); mean age 61years (range 47 to 81); mean delay of surgery 3.5months (range 1 to 6); right shoulder affected in 46 cases (57.5%), left in 34 (42.5%); 22 (27.5%) were isolated lesions, 58 (72.5%) were associated with supraspinatus rupture (SE). The mean improvement was 5.0 points in terms of the VAS and 39.9 points on average in the CMT. New breakage rate, 1.25%. Adverse factors: size of the tear, delay in intervention, women. Patients with type I-B rupture have a better overall result in the CMT than types I-A and III. The longer the delay, the worse results are observed, both for the VAS and the CMT. Women present worse and statistically significant results both in the VAS (P=.00) and in the CMT (P=.01). Conclusions: Excellent and good results have been obtained in this group of patients, but there are adverse factors such as the size of the tear, the duration of the symptoms and the association of other pathologies, especially in women.(AU)

[Translated article] Analysis of the results and adverse factors of arthroscopic repair of degenerative subscapular lesions.

OBJECTIVE: To carry out a review of degenerative subscapularis ruptures (SSC) after their arthroscopic repair and to evaluate whether the results are comparable in terms of pain and function to those of younger patients with traumatic ruptures. METHODS: The data of 80 SSC tears of the 660 rotator cuff tears operated on by the same team of surgeons from June 2008 to June 2018 were retrospectively reviewed. The clinical data of the surgical indications were collected: age, gender, laterality, intervention delay, associated pathologies, location of pain, value of the Visual Analogue Scale (VAS) and the Constant-Murley test (CMT); surgical data were also collected: type and size of lesion, associated biceps injury and associated surgical procedure, coracoid stenosis and associated surgical procedure, number and type of anchors used. A statistical study was performed with multiple linear regression test, parametric tests (Student's t or ANOVA) and non-parametric tests. RESULTS: Of 80 patients, 36 were women (45%) and 44, men (55%); mean age 61 years (range 47-81); mean delay of surgery 3.5 months (range 1-6); right shoulder affected in 46 cases (57.5%), left in 34 (42.5%); 22 (27.5%) were isolated lesions, 58 (72.5%) were associated with supraspinatus rupture (SE). The mean improvement was 5.0 points in terms of the VAS and 39.9 points on average in the CMT. New breakage rate, 1.25%. Adverse factors: size of the tear, delay in intervention, women. Patients with type I-B rupture have a better overall result in the CMT than types I-A and III. The longer the delay, the worse results are observed, both for the VAS and the CMT. Women present worse and statistically significant results both in the VAS (p 0.00) and in the CMT (p 0.01). CONCLUSIONS: Excellent and good results have been obtained in this group of patients, but there are adverse factors such as the size of the tear, the duration of the symptoms and the association of other pathologies, especially in women.

Combination Blockade of the IL6R/STAT-3 Axis with TIGIT and Its Impact on the Functional Activity of NK Cells against Prostate Cancer Cells.

Methods: We analyzed the secretion of cytokines, chemokines, and growth factors in 22Rv1, LNCaP, and DU145 cells. In these cells, we also evaluated the expression of NK ligands, IL6R, STAT-3, and phosporylated STAT-3. In NK-92 cells, we evaluated the effects of Stattic (Stt) and tocilizumab (Tcz) on NK receptors. In addition, we assessed if the disruption of the IL6R/STAT-3 pathway and blockade of TIGIT potentiated the cytotoxicity of NK-92 cells versus DU145 cells. Results: DU145 abundantly secretes M-CSF, VEGF, IL-6, CXCL8, and TGF-ß. Furthermore, the expression of CD155 was found to increase in accordance with aggressiveness and metastatic status in the prostate cancer cells. Stt and Tcz induce a decrease in STAT-3 phosphorylation in the DU145 cells and, in turn, induce an increase of NKp46 and a decrease of TIGIT expression in NK-92 cells. Finally, the disruption of the IL6R/STAT-3 axis in prostate cancer cells and the blocking of TIGIT on NK-92 were observed to increase the cytotoxicity of NK-92 cells against DU145 cells through an increase in sFasL, granzyme A, granzyme B, and granulysin. Conclusions: Our results reveal that the combined use of inhibitors directed against the IL6R/STAT-3 axis and TIGIT enhances the functional activity of NK cells against castration-resistant prostate cancer cells.

Analysis of the results and adverse factors of arthroscopic repair of degenerative subscapular lesions. / Análisis de los resultados y los factores adversos de la reparación artroscópica de las lesiones del subescapular de origen degenerativo.

OBJECTIVE: To carry out a review of degenerative subscapularis ruptures (SSC) after their arthroscopic repair and to evaluate whether the results are comparable in terms of pain and function to those of younger patients with traumatic ruptures. METHODS: The data of 80 SSC tears of the 660 rotator cuff tears operated on by the same team of surgeons from June 2008 to June 2018 were retrospectively reviewed. The clinical data of the surgical indications were collected: age, gender, laterality, intervention delay, associated pathologies, location of pain, value of the Visual Analogue Scale (VAS) and the Constant-Murley test (CMT); surgical data were also collected: type and size of lesion, associated biceps injury and associated surgical procedure, coracoid stenosis and associated surgical procedure, number and type of anchors used. A statistical study was performed with multiple linear regression test, parametric tests (Student's t or ANOVA) and non-parametric tests. RESULTS: Of 80 patients, 36 were women (45%) and 44, men (55%); mean age 61years (range 47 to 81); mean delay of surgery 3.5months (range 1 to 6); right shoulder affected in 46 cases (57.5%), left in 34 (42.5%); 22 (27.5%) were isolated lesions, 58 (72.5%) were associated with supraspinatus rupture (SE). The mean improvement was 5.0 points in terms of the VAS and 39.9 points on average in the CMT. New breakage rate, 1.25%. Adverse factors: size of the tear, delay in intervention, women. Patients with type I-B rupture have a better overall result in the CMT than types I-A and III. The longer the delay, the worse results are observed, both for the VAS and the CMT. Women present worse and statistically significant results both in the VAS (P=.00) and in the CMT (P=.01). CONCLUSIONS: Excellent and good results have been obtained in this group of patients, but there are adverse factors such as the size of the tear, the duration of the symptoms and the association of other pathologies, especially in women.

When to use a prophylactic mesh after stoma closure: a case-control study.

PURPOSE: The closure of a stoma is frequently associated with an acceptable morbidity and mortality. One of the most frequent complications is incisional hernia at the stoma site, which occurs in 20%-40% of cases, higher than incisions in other parts of the abdomen. The objective of this study was to identify the risk factors associated with the presentation of incisional hernia after stoma closure, this in order to select patients who are candidates for prophylactic mesh placement during closure. METHODS: An unpaired case-control study was conducted. This study involved 164 patients who underwent a stoma closure between January 2014 and December 2019. Associated factors for the development of incisional hernia at the site of the stoma after closure were identified, for which it was performed a logistic regression analysis. RESULTS: 41 cases and 123 controls were analyzed, with a mean follow-up of 35.21 ± 18.42 months, the mean age for performing the stoma closure was 65.28 ± 14.07 years, the most frequent cause for performing the stoma was malignant disease (65.85%). Risk factor for the development of incisional hernia at the stoma site after its closure was identified as a history of parastomal hernia (OR 5.90, CI95% 1.97-17.68). CONCLUSIONS: The use of prophylactic mesh at stoma closure should be considered in patients with a history of parastomal hernia since these patients present a significantly higher risk of developing a hernia.

Capsaicin attenuates immunosuppression induced by chronic stress in BALB/C mice.

Although acute stress generally exerts positive effects on the immune system, chronic stress typically causes immunosuppression via the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the effects of capsaicin (1.28 mg/kg intraperitoneally [i.p.] for 7 days) on immune parameters were evaluated under conditions of chronic stress. Capsaicin treatment significantly increased the immune response as evaluated by the delayed-type hypersensitivity (DTH) reaction to dinitrofluorobenzene (DNFB) and splenocyte proliferation assays- It also is able to rescue the splenocytes of the apoptosis induced by stress. The capsaicin treatment increased the production of Th1 cytokines and decreased the production of Th2 cytokines and TGF-ß1 in the plasma and culture supernatants of immunosuppressed mice, which is associated with the modulation of Th2 induced by stress cells. Moreover, the production of corticosterone significantly decreased in capsaicin-treated animals as compared to control groups. The capsaicin treatment further attenuated the immunosuppression induced by the corticosterone treatment (40 mg/kg i.p. for 7 days), albeit less potently, as exhibited in the DTH response. Intriguingly, the capsaicin treatment decreased the induction of IL-10, IL-4, and TGF-ß1 through high doses of corticosterone, indicating direct cellular immunomodulation. These results show, that capsaicin is able to modulate chronic stress-induced immunosuppression, mediating corticosterone released inhibition, but also, that capsaicin significantly modulates the pharmacological action of corticosterone in vivo.

Use of polyvinylidene fluoride (PVDF) meshes for ventral hernia repair in emergency surgery.

PURPOSE: The implantation of non-absorbable meshes is the gold standard technique for ventral hernia (VH) repairs. However, emergency surgeries are often related to contaminated/infected fields, where the implantation of prosthetic materials may not be recommendable. Our aim was to evaluate the results of polyvinylidene fluoride (PVDF) meshes used for contaminated and/or complicated VH repairs in the acute setting. METHODS: We conducted a retrospective analysis of patients with VH who underwent emergency surgery involving PVDF meshes, in a tertiary hospital (from November 2013 to September 2019). We analyzed postoperative complications and 1-year recurrence rates. We evaluated the relationships between contamination grade, mesh placement, infectious complications, and recurrences. RESULTS: We gathered data on 123 patients; their mean age was 62.3 years, their mean BMI was 31.1 kg/m2, and their mean CeDAR index was 51.6. 96.4% of patients had a grade 2-3 ventral hernia according to the Rosen index. The mean defect width was 8 cm (IQR 2-18). 93 cases (75.6%) were described as contaminated or dirty surgeries. A PVDF mesh was placed using an IPOM technique in 56.3% of cases, and via interposition location in 39.9%. The one-month recurrence rate was 5.7% and recurrence after one year was 19.1%. The overall mortality rate was 27.6%. Risk of recurrence was related to patients with a Rosen score over 2 (p < 0.001), as well as with postoperative SSI (p = 0.045). Higher recurrence rates were not related to PVDF mesh placement. CONCLUSION: The use of PVDF meshes for emergency VH repairs in contaminated surgeries seems safe and useful, with reasonable recurrence rates, and acceptable infectious complication rates, similar to those published in the literature.

Plasma miRNAs as biomarkers for endometriosis.

STUDY QUESTION: Can plasma miRNAs be used for the non-invasive diagnosis of endometriosis in infertile women? SUMMARY ANSWER: miRNA-based diagnostic models for endometriosis failed the test of independent validation. WHAT IS KNOWN ALREADY: Circulating miRNAs have been described to be differentially expressed in patients with endometriosis compared with women without endometriosis, suggesting that they could be used for the non-invasive diagnosis of endometriosis. However, these studies have shown limited consistency or conflicting results, and no miRNA-based diagnostic test has been validated in an independent patient cohort. STUDY DESIGN, SIZE, DURATION: We performed genome-wide miRNA expression profiling by small RNA sequencing to identify a set of plasma miRNAs with discriminative potential between patients with and without endometriosis. Expression of this set of miRNAs was confirmed by RT-qPCR. Diagnostic models were built using multivariate logistic regression with stepwise feature selection. In a final step, the models were tested for validation in an independent patient cohort. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Plasma of all patients was available in the biobank of the Leuven Endometriosis Centre of Excellence. Biomarker discovery and model development were performed in a discovery cohort of 120 patients (controls = 38, endometriosis = 82), and models were tested for validation in an independent cohort of 90 patients (controls = 30, endometriosis = 60). RNA was extracted with the miRNeasy Plasma Kit. Genome-wide miRNA expression analysis was done by small RNA sequencing using the NEBNext small RNA library prep kit and the NextSeq 500 System. cDNA synthesis and qPCR were performed using the Qiagen miScript technology. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a set of 42 miRNAs with discriminative power between patients with and without endometriosis based on genome-wide miRNA expression profiling. Expression of 41 miRNAs was confirmed by RT-qPCR, and 3 diagnostic models were built. Only the model for minimal-mild endometriosis (Model 2: hsa-miR-125b-5p, hsa-miR-28-5p and hsa-miR-29a-3p) had diagnostic power above chance performance in the independent validation (AUC = 60%) with an acceptable sensitivity (78%) but poor specificity (37%). LIMITATIONS, REASONS FOR CAUTION: The diagnostic models were built and tested for validation in two patient cohorts from a single tertiary endometriosis centre. Further validation tests in large cohorts with patients from multiple endometriosis centres are needed. WIDER IMPLICATION OF THE FINDINGS: Our study supports a possible biological link between certain miRNAs and endometriosis, but the potential of these miRNAs as clinically useful biomarkers is questionable in women with infertility. Large studies in well-described patient cohorts, with rigorous methodology for miRNA expression analysis, sufficient statistical power and an independent validation step, are necessary to answer the question of whether miRNAs can be used as diagnostics markers for endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by a grant from the Research Foundation - Flanders (FWO). A.V., D.F.O. and D.P. are PhD fellows from the FWO. T.D. is vice president and Head of Global Medical Affairs Fertility, Research and Development, Merck KGaA, Darmstadt, Germany. He is also a professor in Reproductive Medicine and Biology at the Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven (University of Leuven), Belgium and an adjunct professor at the Department of Obstetrics and Gynecology in the University of Yale, New Haven, USA. Neither his corporate role nor his academic roles represent a conflict of interest with respect to the work done by him for this study. The other co-authors have no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Regulation of immunophenotype modulation of monocytes-macrophages from M1 into M2 by prostate cancer cell-culture supernatant via transcription factor STAT3.

BACKGROUND: Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3. METHODS: Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays. RESULTS: The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype. CONCLUSIONS: In this study, we showed that the secretion profile of PC3 prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.

Induction of cellular proliferation in a human astrocytoma cell line by a Trypanosoma cruzi-derived antigen: a mechanism of pathogenesis?

Trypanosoma cruzi can compromise the human central nervous system (CNS) during acute infection or reactivation in immune-suppressed hosts. Astrocytes have been identified as targets of T. cruzi's CNS infection in humans. Despite a high degree of parasitism and cellular lysis by T. cruzi in vitro the number of astrocytoma cells did not change when compared to uninfected cultures. This work evaluated cellular proliferation, changes in Major Histocompatibility Complex (MHC) expression as a reflection of antigen processing, and cytokine (IL-6 & IL-8) secretion in a human astrocytoma cell line exposed to a trypomastigote-derived antigen. Light microscopy was used to evaluate the number of cells; MHC molecule expression, cell cycle and cytokine secretion were assessed by flow cytometry. The number of astrocytoma cells increased proportional to the amount of antigen used and the percentage of cells in G2/M phase was higher when compared to control cultures. Antigen exposure increased expression of MHC class II, but not MHC class I in comparison to cultures incubated without antigen. Astrocytoma cell secretion of IL-6 and IL-8 was unaffected by antigen exposure. These results suggest the participation of a trypomastigote-derived mediator that induces astrocytoma cell proliferation without an inflammatory response; which may contribute to the pathogenesis of neurologic Chagas disease.

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia

Purpose: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). Methods: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m2/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann–Whitney U test. Results: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. Conclusions: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase (AU)

No disponible

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia.

PURPOSE: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). METHODS: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m(2)/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. CONCLUSIONS: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.

Aplicabilidad de las nuevas tecnologías a pacientes claudicantes. CReTe: Claudicantes y registro telemático / Using the new technologies in claudication patients: CReTe: Claudication patients and telematic register

OBJETIVO: Presentamos una aplicación informática para teléfonos móviles ideada para el control de sesiones de ejercicio domiciliario en claudicantes. Exponemos también nuestros resultados preliminares. MATERIAL Y MÉTODOS: La aplicación está diseñada para teléfonos móviles con sistema operativo Android, tecnología de geolocalización y conexión de datos. Está conectada a una base de datos codificada que preserva el secreto médico. Los datos que se recogen de las sesiones de ejercicio son la fecha, la hora de inicio y de fin, el tiempo dedicado, el número de las paradas realizadas y la velocidad máxima, la velocidad media global y la velocidad entre paradas. Durante el mes de enero de 2014 se reclutó a aquellos pacientes que aceptaran el estudio, poseyeran y entendieran un dispositivo móvil Android con geolocalización y conexión de datos. Los criterios de exclusión del estudio una vez comenzado fueron progresión hacia isquemia arterial crítica, enfermedad intercurrente grave, fallecimiento y ausencia de comunicación con el paciente. Se recogieron las principales morbilidades y los resultados de los cuestionarios de calidad de vida SF36 y EuroQol 5D. Se midió el tiempo de primera consulta y el tiempo dedicado por semana y paciente durante un seguimiento de 28 días. Se calculó el cumplimiento de las sesiones con respecto a las sesiones pactadas con cada paciente, con un mínimo de 2 semanales. RESULTADOS: Un total de 5 pacientes fueron incluidos, con edad media de 59,3 años (mediana 52; rango 40-80). De ellos 2 se excluyeron, uno por progresión a isquemia crítica y otro por ausencia de comunicación. El tiempo medio dedicado por consulta nueva fue de 29,1 min (mediana 27,5; rango 45-20). El cumplimiento de las sesiones fue del 100% en 2 pacientes y del 63% en otro. El tiempo dedicado en el seguimiento semanal por paciente fue de 1,68 min. CONCLUSIONES: CReTe es una herramienta aplicable a nuestro medio que precisa de estudios mayores para demostrar su utilidad

OBJECTIVE: The preliminary results are presented on the use of a new application for mobile phones designed to control home exercise sessions in claudication. MATERIALS AND METHODS: The application is designed for Android systems with geolocation technology and Internet connection. It is connected to a database encoded to ensure medical confidentiality. The data collected from the exercise sessions were the date, start time and end time, the time spent, the number of stops made, and the maximum speed, average speed and overall speed between stops. During the month of January 2014 patients who accepted and understood the study, and possessed an Android mobile device with geolocation and data connection, were enrolled. The exclusion criteria, 11 the study started, were progression to arterial ischemia, severe intercurrent illness, non-communication with the patient, and death. Major morbidities and results of quality of life questionnaires SF36 and EuroQol 5 D were collected. Time of first consultation and time spent per week per patient during a 28-day follow-up was recorded. Compliance as regards the agreed sessions was calculated for each patient, with a minimum of 2 weeks. RESULTS: The study included 5 patients with a mean age 59.3 years (median 52; range 40-80). Of these, 2 were excluded, one for progression to critical ischemia and another for non-communication. The average time spent in a new consultation was 29.1 minutes (median 27.5, range 45-20). The compliance with the sessions was 100% in 2 patients, and 63% in another. Time spent in the weekly monitoring per patient was 1.68 minutes. CONCLUSIONS: CReTe is an applicable tool in our environment that requires further study to demonstrate its usefulness

FT-IR and FT-Raman spectra of 5-fluoroorotic acid with solid state simulation by DFT methods.

FT-Raman and FT-IR studies of the biomolecule 5-fluoroorotic acid in the solid state were carried out. The unit cell found in the crystal was simulated as a tetramer form by density functional calculations. They were performed to clarify wavenumber assignments of the experimental observed bands in the spectra. Correlations with the molecule of uracil were made, and specific scale equations were employed to scale the wavenumbers of 5-fluoroorotic acid. Good reproduction of the experimental wavenumbers is obtained and the % error is very small in the majority of the bands. This fact confirms our simplified solid state model. The molecular structure was fully optimized using DFT and MP2 methods. The relative stability of both the syn and anti conformations was investigated, and the anti-form was found to be slightly more stable, by 7.49 kJ/mol at the MP2 level. The structures of all possible tautomeric forms were determined. The keto-form appeared as the most stable one. The NBO atomic charges and several thermodynamic parameters were also calculated.

Usefulness of serum lipid peroxide as a diagnostic test for hypoxic ischemic encephalopathy in the full-term neonate.

OBJECTIVE: To evaluate the usefulness of serum lipid peroxide (LPO) for hypoxic ischemic encephalopathy (HIE) in full-term neonates. STUDY DESIGN: Diagnostic test evaluation forming three groups: (1) healthy full-term neonates (n=59), (2) at-risk full-term neonates without HIE (n=57) and (3) at-risk full-term neonates with HIE (n=57). HIE diagnosis was made using the Finer clinical classification at 48 h after birth. Serum LPO was taken at 4 h after birth and determined by spectrophotometry. RESULT: One hundred seventy-three full-term neonates were studied. Fifty-one of the at-risk full-term neonates with HIE (51/57) had high serum LPO and two of the at-risk full-term neonates without HIE (2/57) (P<0.001). Serum LPO level had 89% sensitivity, 96% specificity, 96% positive predictive value, 90% negative predictive value, 24 positive probability ratio, 0.11 negative probability ratio and 92% diagnostic usefulness. CONCLUSION: Serum LPO level could be a useful test for early diagnosis of HIE in full-term neonates.

Comparación de la eficacia y seguridad de la terapia combinada de cardiomioplastia celular con el factor estimulante de colonias de granulocitos en pacientes con cardiopatía isquémica en dos vías de implatación / Comparison of efficacy and safety of combined therapy of cellular cardiomyoplasty and granulocyte colony stimulating factor in patients with ischemic cardiomyopathy in two routes of implantation

Este estudio tiene como objetivo evaluar la eficacia y seguridad de la terapia combinada de cardiomioplastia celular con el factor estimulante de colonias de granulocitos en pacientes con cardiopatía isquémica, y explorar posibles diferencias entre la vía de implantación. METODOLOGÍA: se hizo un estudio de ®antes y después¼ para datos longitudinales en el que se compararon variables ecocardiográficas y número de MET alcanzados en la prueba de esfuerzo antes, dos, seis y doce meses después del procedimiento; así mismo, se evaluaron la mortalidad y los efectos adversos de la terapia. Se exploraron diferencias en los resultados de acuerdo con la vía de implantación intracoronaria vs. epicárdica. RESULTADOS: se incluyeron dieciocho pacientes, 62,3% hombres, cuya edad promedio fue 49,4 ± 11,7 años y la fracción de eyección promedio fue 31% ± 0,04. La implantación se realizó por vía intracoronaria en doce pacientes y por vía epicárdica en seis. La mediana de fracción de eyección antes de la implantación de las células fue de 30% con un rango intercuartil de 28%-35% y la media de los MET fue de 6 con un rango intercuartil de 5-7; ambas variables, al igual que los volúmenes ventriculares de fin de diástole y sístole se incrementaron de forma significativa después del procedimiento, con tendencia a un mayor incremento de la fracción de eyección en el grupo de pacientes cuya vía de implantación fue la epicárdica en comparación con la vía intracoronaria; sin embargo, el número de pacientes en cada subgrupo impidió hacer análisis definitivos. Un paciente tuvo infección de la herida quirúrgica y tres murieron dos meses después de la implantación (uno de shock séptico y dos de shock cardiogénico)...

The objective of this study is to assess efficacy and safety of combined therapy of cellular cardiomyoplasty and granulocyte colony stimulating factor in patients with ischemic cardiomyopathy and explore possible differences between the implantation routes. METHODOLOGY: we performed a before and after study for longitudinal data comparing echocardiographic variables and number of Met achieved in the stress test before and at two, six and twelve months after the procedure. Likewise, mortality and adverse therapy effects were evaluated. Differences in the results were analyzed according to the intracoronary vs. epicardiac route of implantation. RESULTS: eighteen patients were included; 62,3% men, with mean age 49.4 ± 11,7 years. Mean ejection fraction was 31% ± 0,04. In twelve patients implantation was performed by intracoronary route and in six by epicardiac route. Mean ejection fraction before cell implantation was 30% with an interquartil range (IQR) of 28-35%, and MET average was 6 with an interquartil rage of 5-7. Both variables as well as end-systolic and end-diastolic volumes increased significantly after the procedure, with a tendency to greater increase in ejection fraction in the group of patients whose route was epicardial implantation compared with intracoronary route; however, the number of patients in each subgroup prevented to make a definitive analysis. One patient had surgical wound infection and three died two months after implantation (one of septic shock and two of cardiogenic shock). CONCLUSION: in our environment the performance of combination therapy with cellular cardiomyoplasty and granulocyte colony stimulating factor is feasible. This is a safe procedure that achieved a sustained improvement in ejection fraction and MET beyond benefits achieved with revascularization and optimal pharmacological therapy.

Specific pattern of flea antigen recognition by IgG subclass and IgE during the progression of papular urticaria caused by flea bite

Background: Papular urticaria caused by flea bite presents clinical symptoms of a hypersensitivity reaction accompanied by skin lesions. However, the pattern of recognition by different antibody isotypes during the progression of the disease is unknown. This study evaluated variations in immunoglobulin E and immunoglobulin G subclass antibody responses to flea antigens during the progression of papular urticaria caused by flea bite. Methods: Twenty-five patients clinically diagnosed with papular urticaria due to flea bite were included. Ten healthy children were included as controls. Recognition of antigens from complete flea body extract by patients and healthy controls was determined using immunoblot assays. Results: The results revealed that patients with 2–5 years of papular urticaria evidenced more IgE bands than those with shorter or longer durations of symptoms. In contrast, healthy children showed a predominance of immunoglobulin G1 and immunoglobulin G3. The majority of the recognised antigens were low molecular weight proteins (<90kDa). Proteins with molecular weights between 16-20, 21-25, and 31-35kDa showed different patterns of recognition between patients and healthy children. Conclusion: The predominant specific antibody isotypes vary according to the time elapsed since the onset of symptoms in papular urticaria caused by flea bite

No disponible