Intraovarian platelet-rich plasma injection and IVF outcomes in patients with poor ovarian response: a double-blind randomized controlled trial.

STUDY QUESTION: Does platelet-rich plasma (PRP) intraovarian injection increase the number of retrieved oocytes in successive ovarian punctions among patients with poor ovarian reserve (POR)? SUMMARY ANSWER: The injection of PRP increases the number of retrieved oocytes without increasing the quality of developed blastocysts. WHAT IS KNOWN ALREADY: Management of women with reduced ovarian response to stimulation is one of the significant challenges in reproductive medicine. Recently, PRP treatment has been proposed as an adjunct in assisted reproduction technology, with controversial results. STUDY DESIGN, SIZE, DURATION: This placebo-controlled, double-blind, randomized trial included 60 patients with POR stratified according to the POSEIDON classification groups 3 and 4. It was conducted to explore the efficacy and safety of intraovarian PRP injection. Patients were proposed to undergo three consecutive ovarian stimulations to accumulate oocytes and were randomized to receive either PRP or placebo during their first oocyte retrieval. Randomization was performed using computer-generated randomization codes. Double blinding was ensured so that neither the participant nor the investigators knew of the treatment allotted. All patients underwent three ovarian stimulations and egg retrieval procedures. ICSI was performed after a third ovarian puncture. The primary endpoint was the number of mature oocytes retrieved after PRP or placebo injection in successive ovarian punctures. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty women (30-42 years) fulfilling inclusion criteria were randomized in equal proportions to the treatment or control groups. MAIN RESULTS AND THE ROLE OF CHANCE: The baseline demographic and clinical characteristics [age, BMI, anti-Müllerian hormone (AMH) levels] were comparable between the groups. Regarding the primary endpoint, the cumulative number (mean ± SEM) of retrieved mature oocytes was slightly higher in the treatment group: 10.45 ± 0.41 versus 8.91 ± 0.39 in the control group, respectively (95% CI of the difference 0.42-2.66; P = 0,008). The number of mature oocytes obtained among all patients increased in successive egg retrievals: 2.61 ± 0.33 (mean ± SEM) in punction 1 (P1), 3.85 ± 0.42 in P2, and 4.73 ± 0.44 in P3. However, the increase was higher among patients receiving the assessed PRP treatment. In P2, the number of retrieved mature oocytes was 4.18 ± 0.58 versus 3.27 ± 0.61 in controls (95% CI of the difference: -0.30 to 2.12; P = 0.138) and in P3, 5.27 ± 0.73 versus 4.15 ± 0.45 (95% CI of the difference: 0.12-2.12; P = 0.029). The mean ± SEM number of developed and biopsied blastocysts was 2.43 ± 0.60 in the control group and 1.90 ± 0.32 in the treatment group, respectively (P = 0.449). The mean number of euploid blastocysts was 0.81 ± 0.24 and 0.81 ± 0.25 in the control and treatment groups, respectively (P = 1.000). The percentages of patients with euploid blastocysts were 53.33% (16 out of 30) and 43.33% (13 out of 30) for patients in the control and treatment groups, respectively (Fisher's exact test P = 0.606). The overall pregnancy rate per ITT was 43% (26 out of 60 patients). However, the percentage of clinical pregnancies was higher in the control group (18 out of 30, 60%) than in the treatment group (8 out of 30, 27%) (P = 0.018). There was also a trend toward poorer outcomes in the treatment group when considering full-term pregnancies (P = 0.170). There were no differences between control and treatment groups regarding type of delivery, and sex of newborns. LIMITATIONS, REASONS FOR CAUTION: The mechanism of the potential beneficial effect of PRP injection on the number of retrieved oocytes is unknown. Either delivered platelet factors or a mechanical effect could be implicated. Further studies will be needed to confirm or refute the data presented in this trial and to specify the exact mechanism of action, if any, of PRP preparations. WIDER IMPLICATIONS OF THE FINDINGS: The increasing number of women with a poor response to ovarian stimulation supports the exploration of new areas of research to know the potential benefits of therapies capable of increasing the number of oocytes available for fertilization and improving the quality of developed blastocysts. An increase in the retrieved oocytes in both arms of the trial suggests that, beyond the release of growth factor from platelets, a mechanical effect can play a role. However, neither improvement in euploid blastocyst development nor pregnancy rates have been demonstrated. STUDY FUNDING/COMPETING INTEREST(S): This trial was supported by Basque Government and included in HAZITEK program, framed in the new Euskadi 2030 Science and Technology Plan (PCTI 2030). These aids are co-financed by the European Regional Development Fund (FEDER). The study funders had no role in the study design, implementation, analysis, manuscript preparation, or decision to submit this article for publication. No competing interests are declared by all the authors. TRIAL REGISTRATION NUMBER: Clinical Trial Number EudraCT 2020-000247-32. TRIAL REGISTRATION DATE: 3 November 2020. DATE OF FIRST PATIENT'S ENROLLMENT: 16 January 2021.

Multicenter validation of Early Warning Scores for detection of clinical deterioration in COVID-19 hospitalized patients.

Objective: Investigate the predictive value of NEWS2, NEWS-C, and COVID-19 Severity Index for predicting intensive care unit (ICU) transfer in the next 24 h. Design: Retrospective multicenter study. Setting: Two third-level hospitals in Argentina. Patients: All adult patients with confirmed COVID-19, admitted on general wards, excluding patients with non-intubated orders. Interventions: Patients were divided between those who were admitted to ICU and non-admitted. We calculated the three scores for each day of hospitalization. Variables: We evaluate the calibration and discrimination of the three scores for the outcome ICU admission within 24, 48 h, and at hospital admission. Results: We evaluate 13,768 days of hospitalizations on general medical wards of 1318 patients. Among these, 126 (9.5%) were transferred to ICU. The AUROC of NEWS2 was 0.73 (95%CI 0.68-0.78) 24 h before ICU admission, and 0.52 (95%CI 0.47-0.57) at hospital admission. The AUROC of NEWS-C was 0.73 (95%CI 0.68-0.78) and 0.52 (95%CI 0.47-0.57) respectively, and the AUROC of COVID-19 Severity Index was 0.80 (95%CI 0.77-0.84) and 0.61 (95%CI 0.58-0.66) respectively. COVID-19 Severity Index presented better calibration than NEWS2 and NEWS-C. Conclusion: COVID-19 Severity index has better calibration and discrimination than NEWS2 and NEWS-C to predict ICU transfer during hospitalization.

Objetivo: Investigar el valor predictivo de los scores NEWS2, NEWS-C y COVID-19 Severity Index para predecir la transferencia de urgencia a la unidad de cuidados intensivos (UCI) en las próximas 24 horas. Diseño: Estudio multicéntrico retrospectivo. Ámbito: Dos hospitales de tercer nivel en Argentina. Pacientes: Pacientes adultos con COVID-19, ingresados en salas generales, excluyendo pacientes con órdenes de no intubar. Intervenciones: Se dividió a los pacientes entre los que ingresaron en la UCI y los que no ingresaron. Calculamos las tres puntuaciones para cada día de hospitalización. Variables: Evaluamos la calibración y discriminación de las tres puntuaciones para predecir el traslado de urgencia a UCI en las 24, 48 h previas al pase a UCI y al ingreso hospitalario. Resultados: Evaluamos 13.768 días de hospitalización en internación general de 1.318 pacientes, de los cuales 126 (9,5%) fueron trasladados a UCI. El AUROC del NEWS2 fue de 0,73 (IC 95% 0,68-0,78) 24 h antes del ingreso en UCI y de 0,52 (IC 95% 0,47-0,57) al ingreso hospitalario. El AUROC de NEWS-C fue de 0,73 (IC 95% 0,68-0,78) y 0,52 (IC 95% 0,47-0,57) respectivamente, y el AUROC del COVID-19 Severity Index fue de 0,80 (IC 95% 0,77-0,84) y 0,61 (IC 95% 0,58-0,66) respectivamente. El COVID-19 Severity Index presentó una mejor calibración que NEWS2 y NEWS-C. Conclusión: El COVID-19 Severity Index presentó una mejor calibración y discriminación que NEWS2 y NEWS-C para predecir la transferencia de la UCI durante la hospitalización.

Allergen Profile of London Plane Tree Pollen: Clinical and Molecular Pattern in Central Spain.

BACKGROUND AND OBJECTIVES: Platanus acerifolia (London plane tree) is a deciduous tree of the Platanaceae family. Sensitization to this plant varies with geography. Madrid, located in central Spain, has one of the highest London plane tree pollen concentration levels on the Iberian Peninsula. We evaluated both the clinical characteristics and the molecular sensitization pattern of patients with allergy to London plane tree pollen in the region of Madrid. METHODS: Thirty-eight patients allergic to London plane tree pollen were selected according to their clinical symptoms and positive results in skin prick testing and/or specific IgE determination. Serum was collected, and allergen components were evaluated using immunodetection techniques as well as ImmunoCAP. The IgE-binding proteins detected were identified and characterized using mass spectrometry. RESULTS: Analysis of serum samples from allergic patients revealed 9 IgE-binding bands in London plane tree pollen extract. Among these, the 45-kDa protein, which corresponded to Pla a 2, was detected in 76.3% of patients. However, the 18-kDa (Pla a 1) and 9-kDa (Pla a 3) bands were detected in 44.7% and 23.7% of sera, respectively. These results were confirmed using purified proteins. Characterization of the allergen revealed the 27-kDa protein to be glutathione-S-transferase. CONCLUSIONS: The molecular profile of patients sensitized to London plane tree pollen differs from that reported in studies from other locations. In the population we studied, the prevalence of Pla a 2 was higher than that of Pla a 1 and Pla a 3. In addition, the minor allergen previously referred to as Pla a 4 was characterized as glutathione-S-transferase.

Association Between the Seed Storage Proteins 2S Albumin and 11S Globulin and Severe Allergic Reaction After Flaxseed Intake.

BACKGROUND: Given the increased popularity of flaxseed in meals, several cases of allergy to these seeds have been reported. Little is known about the allergens implicated in hypersensitivity reactions to flaxseed. The present study aimed to identify the allergens involved in IgE-mediated reactions in 5 patients with a clinical history of severe systemic symptoms after flaxseed consumption. METHODS: Proteins that were potential allergens with IgE-binding capacity were purified from flaxseed extract using chromatography and identified via MALDI-TOF mass spectrometry. Immunoassays were performed using the 5 allergic patients' sera tested individually and as a pool. RESULTS: Immunoblotting of the flaxseed extract revealed a low-molecular-mass protein (around 13 kDa) in 4 of the 5 patients, while a protein of approximately 55 kDa was detected in 2 patients. The proteins were identified by mass spectrometry as flaxseed 2S albumin, which is included in the WHO/IUIS allergen nomenclature as Lin u 1, and 11S globulin. Inhibition assays revealed in vitro IgE-mediated cross-reactivity between Lin u 1 and peanut and cashew nut proteins, while IgE-mediated recognition of 11S globulin by patients' sera was partially inhibited by several plant-derived sources. CONCLUSIONS: Seed storage proteins from flaxseed were involved in the development of severe symptoms in the 5 patients studied and exhibited cross-reactivity with other allergenic sources. Besides the severity of flaxseed allergy in patients sensitized to 2S albumin, this is the first time that 11S globulin has been identified as a potential allergen. Taking these data into account should ensure a more accurate diagnosis.

Psychosocial repercussion of migraine: is it a stigmatized disease?

INTRODUCTION: Stigma manifests both in prejudices and rejection from society towards patients who suffer from a specific pathology, and by patient's internalization of this discrimination, with the consequent repercussions on their state of mind and quality of life. The aim of the study was to quantify the stigma associated with migraine and analyze whether it is related to the clinical-demographic characteristics of the patients, as well as the possible impact on their daily lives. MATERIALS AND METHODS: The stigma scale for chronic illness (SSCI) and other questionnaires were administered to 56 patients with episodic migraine (EM), 18 with chronic migraine (CM), and 21 with epilepsy, as a control group. RESULTS: The mean SSCI score was higher (51.6 ± 15.0) in the CM group than in the EM (45.0 ± 13.5) and epilepsy (47.6 ± 15.5) groups, without reaching statistical significance. In addition, the score was higher in patients who were unemployed, divorced, and in those who had migraine with aura. A statistically significant correlation was found between the SSCI score and the impact of migraine on daily life, the presence of stress, anxiety and depression, and low self-esteem. CONCLUSIONS: There is a stigma around migraine in our society, which seems to be more prevalent in patients with certain socio-demographic characteristics, and that is related to stress, mood alterations, and low self-esteem. Trying to reduce stigma could contribute to improve the control of migraine and reduce the impact of the disease at a socio-economic level.

Randomized clinical trial to assess the mPADSS scale in recovery and home discharge after endoscopy.

BACKGROUND: current clinical practice guidelines recommend the use of objective scales as a criterion for post-endoscopy sedation discharge. OBJECTIVE: to assess the recovery time, complications and patient satisfaction level using the mPADSS scale. MATERIAL AND METHODS: demographic data and medical history were collected. Vital signs, anxiety and abdominal pain were measured pre-endoscopy. Patients were randomized into a control group, discharged according to the usual practice, and the intervention group, who underwent the mPADSS scale every ten minutes, until an objective score was reached. RESULTS: one hundred and eighteen patients were randomized (78 colonoscopies, 32 gastroscopies, three gastro + colonoscopies and 15 endoscopic retrograde cholangiopancreatographies/endoscopic ultrasound [ERCP/USE]). With regard to medical history, there were 36 cases of elevated blood pressure and 19 diabetes cases, 15 with anticoagulant/antiplatelet and 21 with hypnotic/anxiolytic medication. An average of 160 mg of propofol was required per patient, with additional flumazenil and midazolam in 49. There were two episodes of vomiting and three of mild desaturation, all of them in the control group. Sixty patients were included in the control group and 58 in the mPADSS group, who were discharged in 15 and 10 minutes on average respectively (p < 0.005); 24-48h telephone call follow-up data were available for 105 subjects. There were four readmissions (three control and one mPADSS). There were no differences in pain and post-sedation symptoms and the level of satisfaction in terms of attention and duration of stay was similar in both groups. CONCLUSIONS: this study shows the efficiency, safety and patient satisfaction using the mPADSS scale. Thus, its use is recommend.

[Is there a difference in the postoperative follow up of ureteropelvic junction obstruction according to age?] / ¿Existe diferencia en la evolución postoperatoria de la estenosis pieloureteral según la edad?

OBJECTIVE: To compare postoperative follow up in patients older and younger than 12 months who underwent surgical treatment of ureteropelvic junction obstruction (UJO). MATERIAL AND METHODS: Retrospective study of 77 patients, 78 kidney units, intervened from UJO (2007-2014). We analyzed epidemiological, clinical, echographic, and pre and postoperative renogram variables, outcomes and complications. We divided the patients into 2 groups according to age: group A ≤ 12 months and group B > 12 months, comparing the results by statistical analysis, considering p < 0.05 statistically significant. RESULTS: Group A: 38 patients, 26 males (68.4%), one bilateral UJO and 22 rights (57.9%), 36 prenatal diagnoses (92.3%) and mean age of intervention 5.28 months [range 0.24 -11,28]. We performed 9 minilumbotomies, 29 assisted by retroperitoneoscopy (ARP) and 1 pneumatic dilation (PD). Group B: 39 patients, 26 males (66.7%), 10 rights (25.64%), 19 prenatal diagnoses (48.7%) and mean age 6.13 years [range 1.13-14.52]. 15 minilumbotomies, 20 ARP, 3 laparoscopic and 1 PD. Preoperative mean renal function (MRF) of group A: 35.9 ± 13.4 [range 8-57] vs. 39.74 ± 13.91 [range 9-57] in group B (p = 0.347). Postoperative MRF 43.29 ± 18.2 [range 12-100] group A and 39.41 ± 12.89 [range 11-54] group B (p = 0.464). Group A and B: 11 and 8 complications, respectively (p = 0.429). We did not find statistically significant differences in the mean preoperative anteroposterior diameter (DAP) between both groups (p = 0.313). We compared DAP at 3, 6, 12, 24 and 48 postoperative months, observing a greater reduction of DAP from group A compared to B; however, we found only statistically significant differences in DAP at 3 months postoperatively (p = 0.047). CONCLUSION: Renal DAP is reduced postoperatively more in patients younger than 1 year. Moreover, an improvement of the DRF after pieloplasty can be observed despite not being statistically significant.

OBJETIVO: Comparar la evolución postquirúrgica en pacientes mayores y menores de 12 meses intervenidos de estenosis pieloureteral (EPU). MATERIAL Y METODOS: Estudio retrospectivo de 77 pacientes, 78 unidades renales, intervenidos por EPU (2007-2014). Analizamos variables epidemiológicas, clínicas, ecográficas y de renogramas pre y postoperatorios, resultados y complicaciones. Dividimos a los pacientes en 2 grupos según la edad: grupo A ≤ 12 meses y grupo B > 12 meses, comparando los resultados mediante análisis estadísticos (p < 0,05 estadísticamente significativo). RESULTADOS: Grupo A: 38 pacientes, 26 varones (68,4%), una EPU bilateral y 22 derechas (57,9%), 36 diagnósticos prenatales (92,3%) y edad media de intervención 5,28 meses [rango 0,24-11,28]. Realizamos 9 minilumbotomías, 29 asistidas por retroperitoneoscopia (ARP) y una dilatación neumática (DN). Grupo B: 39 pacientes, 26 varones (66,7%), 10 derechas (25,64%), 19 diagnósticos prenatales (48,7%) y edad media 6,13 años [rango 1,13-14,52]. Realizamos 15 minilumbotomías, 20 ARP, 3 laparoscópicas y 1 DN. Función renal diferencial media (FRDM) preoperatoria del grupo A: 35,9 ± 13,4 [rango 8-57] vs. 39,74 ± 13,91 [rango 9-57] grupo B (p = 0,347). FRDM postoperatoria 43,29 ± 18,2 [rango 12-100] grupo A y 39,41 ± 12,89 [rango 11-54] grupo B (p = 0,464). Grupos A y B: 11 y 8 complicaciones, respectivamente (p = 0,429). No encontramos diferencias estadísticamente significativas en la media del diámetro anteroposterior (DAP) de la pelvis preoperatoria entre ambos grupos (p = 0,313). Comparamos los DAP a los 3, 6, 12, 24 y 48 meses postoperatorios, observando una reducción mayor del DAP del grupo A frente al B, sin embargo, solo encontramos diferencias estadísticamente significativas en el DAP a los 3 meses postoperatorios (p = 0,047). CONCLUSION: El DAP de la pelvis renal se reduce más en los pacientes menores de 1 año a los 3 meses postoperatorios. Además, podemos observar una evidente mejoría de la FRDM tras la pieloplastia a pesar de no encontrar diferencias estadísticamente significativas.

Association between exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prior to septic shock and acute kidney injury.

OBJECTIVE: To evaluate the association between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use prior to a septic shock episode and the development, prognosis and long-term recovery from acute kidney injury (AKI). DESIGN: A single-centre, prospective observational study was carried out between September 2005 and August 2010. SCOPE: Patients admitted to the ICU of a third level hospital. PATIENTS: A total of 386 septic shock patients were studied. INTERVENTIONS: None. VARIABLES OF INTEREST: Use of ACEIs/ARBs, AKI development, recovery of previous creatinine levels and time to recovery. RESULTS: A total of 386 patients were included, of which 312 (80.8%) developed AKI during ICU stay and 23% were receiving ACEIs/ARBs. The percentage of patients on ACEIs/ARBs increased significantly in relation to more severe stages of AKI irrespective of the kind of AKI score. After adjusting for confounders, the development of AKI was independently associated to the use of ACEIs/ARBs (OR 2.19; 95%CI 1.21-3.84; p=.04). With respect to the recovery of kidney function, the group of patients on ACEIs/ARBs had significantly higher creatinine levels at ICU discharge and needed hemodialysis more frequently thereafter. However, use of ACEIs/ARBs affected neither recovery of previous creatinine levels nor significantly delayed recovery. CONCLUSIONS: The use of ACEIs/ARBs before septic shock episodes was correlated to AKI development and severity, but did not affect the recovery of kidney function after sepsis resolution.

[The diagnosis of pilomatrixoma in children is not as easy as it may seem. A review of 126 cases]. / El diagnóstico del pilomatrixoma infantil no es tan fácil como parece: revisión de 126 casos.

OBJECTIVE: To describe our experience with pilomatrixomas, clinical presentation, clinical accuracy, associated diseases, and surgical treatment. METHODS: A retrospective review of patients with a pathology report of an excised pilomatrixoma between 2011 and 2014. Data regarding gender, age of intervention, number of masses, size, location, and preoperative clinical diagnosis, pathology report, recurrences, and associated diseases were collected. Statistical analysis was performed using EPIinfo 7.1.5. RESULTS: A total of 151 tumors in 138 patients were removed, 25 were excluded for having a clinical diagnosis of pilomatrixoma without confirmation of the pathology report. The remaining 126 cases have an average age of 8.26 years (range 1-14 years) and 50.72% are males. The tumors were located above the umbilicus in 97% of the cases, with a higher concentration of 50.72% in the head and neck. The clinical diagnosis corresponds with the pathology report in 69.05% of cases. Out of these confirmed cases the most frequent differential diagnosis is cystic lesion (11.90%) and dermoid cyst (10.22%). There were no cases of malignant degeneration. The average diameter is 1.13 cm, there were no recurrences, but there were 11 cases of a new lesion in a different location. There is no statistical association with other pathologies. The most frequent diseases found were obesity (3.62%) and attention deficit syndrome (3.62%). CONCLUSION: The pilomatrixoma is a tumor that appears predominantly in the head and neck, and has a difficult clinical diagnosis. Complete removal is curative, although it does not prevent the appearance of new lesions.

OBJETIVO: Describir nuestra experiencia con pilomatrixomas, examinando la presentación clínica, acierto clínico, enfermedades asociadas y tratamiento quirúrgico. MATERIAL Y METODOS: Estudio retrospectivo de los pacientes con diagnóstico anatomo-patológico (AP) de pilomatrixoma, en el periodo de 2011 a 2014. Se recopilaron datos sobre genero, edad de intervención, número de tumoraciones, tamaño, localización, diagnóstico preoperatorio, anatomía patológica, reintervenciones y patología asociada. Se realizó el análisis estadístico con EPIinfo 7.1.5. RESULTADOS: Se extirparon un total de 151 tumores en 138 pacientes, excluyendo 25 tumoraciones por tener diagnóstico clínico de pilomatrixoma sin confirmación patológica. Los 126 casos que tienen confirmación AP de pilomatrixoma tienen una edad media de exéresis de 8,26 años de edad (1-14 años) y el 50,72% son del género masculino. El 97% de los tumores se localizan por encima del ombligo, concentrándose en la cabeza y cuello el 52,9%. La sospecha clínica corresponde con AP en el 69,05%. De los casos confirmados, los diagnósticos clínicos diferenciales más frecuentes son lesión quística (11,90%) y quiste dermoide (10,22%); no hubo pilomatrixomas con degeneración maligna. La media de diámetro es de 1,13 cm, no hubo recidivas locales, pero sí 11 nuevos casos de pilomatrixomas en otra localización. No hay asociación estadísticamente significativa a otras patologías. Las enfermedades más frecuentes encontradas son la obesidad (3,62%) y el síndrome de déficit de atención (3,62%). CONCLUSION: El pilomatrixoma es una tumoración predominantemente de aparición en cara y cuello, de difícil diagnóstico clínico. La exéresis completa es curativa, aunque no previene la aparición de nuevas lesiones.

Serum palmitoleate acts as a lipokine in subjects at high cardiometabolic risk.

BACKGROUND AND AIM: Clinical data on the role as a lipokine of de novo lipogenesis-derived palmitoleic acid (C16:1n-7cis) in serum non-esterified fatty acids (palmitoleate) are scarce. We aimed to assess whether palmitoleate relates to cardiometabolic risk. METHODS AND RESULTS: In this cross-sectional study we included 358 individuals aged 30-65-years at high cardiovascular risk. We tested the association of palmitoleate (determined by gas chromatography) with metabolic syndrome (MS) and its components (defined by ATPIII criteria), fatty liver index (a surrogate of non-alcoholic fatty liver disease [NAFLD]), and subclinical atherosclerosis (determined as ultrasound-measured carotid intima-media thickness and arterial stiffness). Palmitoleate concentration was higher in women compared with men (median ± range interquartile, 1.36 ± 0.96 vs. 0.97 ± 0.77 µmol/L respectively, P < 0.001). In both genders palmitoleate concentration was associated with a higher prevalence of MS: men, odds ratio [OR: 1.12 (95%CI: 1.03; 1.23, P = 0.010)]; women [OR: 1.07 (95%CI: 1.03; 1.13, P = 0.005)], and all of its components except low HDL-cholesterol and hypertriglyceridemia. Palmitoleate was also associated with increased risk of NAFLD in both men [OR: 1.12 (95%CI: 1.03; 1.29, P = 0.031)] and women [OR: 1.11 (95%CI: 1.05; 1.19, P = 0.001)]. No associations with subclinical atherosclerosis were detected. CONCLUSIONS: Our observational data supports a relationship between de novo lipogenesis-derived circulating palmitoleic acid (palmitoleate) and increased cardiometabolic risk.

Jaagsiekte Sheep Retrovirus Can Reach Peyer's Patches and Mesenteric Lymph Nodes of Lambs Nursed by Infected Mothers.

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). It is generally accepted that transmission by the respiratory route occurs under natural conditions. However recent studies strongly indicate that JSRV can also be transmitted to lambs perinatally via colostrum and milk (C/M). The aim of this work was to confirm that C/M can transmit JSRV infection to lambs under natural conditions and investigate the initial events associated with this transmission route. We have analyzed the presence of JSRV in C/M samples from 22 naturally infected, asymptomatic ewes throughout a lactation period, and in various tissues collected from a group of 36 of their lambs that were fed naturally. The lambs were euthanized at 12, 24, 48, and 72 hours and at 5 and 10 days after birth. We detected JSRV-provirus by PCR in the somatic C/M cells from 10/22 ewes (45.45%). The virus was also detected in 9/36 lambs (25%). JSRV-infected cells, with lymphoreticular-like morphology, were observed by immunohistochemistry (IHC) and in situ hybridization (ISH) in Peyer's patches (PP) from the small intestine of the youngest lambs and in mesenteric lymph nodes (MLN) from lambs older than 72 hours. The virus was also detected by PCR in white blood cells (WBC) in 2/36 lambs (5.5%). These results confirm colostral transmission of JSRV to lambs under natural conditions. Infected lymphoreticular cells contained in C/M appear to be involved. These cells can cross the intestinal barrier of newborn lambs, reach the MLN and enter into circulation.

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

BACKGROUND: Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. METHODS: ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. RESULTS: SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. CONCLUSION: ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE.

FABP4 plasma concentrations are determined by acquired metabolic derangements rather than genetic determinants.

BACKGROUND AND AIMS: Circulating FABP4 is strongly associated with metabolic and cardiovascular risk (CVR) and has been proposed as a new risk biomarker. Several FABP4 gene polymorphisms have been associated with protein expression in vitro and metabolic and vascular alterations in vivo. The aim of this study is to evaluate the impact of FABP4 polymorphisms on FABP4 plasma levels and subclinical arteriosclerosis in patients with obesity, metabolic syndrome (MS) or type 2 diabetes (T2DM). METHODS AND RESULTS: We studied 440 individuals with obesity, MS, T2DM or other cardiovascular risk conditions who attended the vascular medicine and metabolism unit of our hospital. Anamnesis, physical examination and anthropometry data were recorded. Standard biochemical parameters were determined. Plasma FABP4 concentrations were measured. Carotid intima-media thickness (cIMT) was assessed using ultrasonography. The following FABP4 gene single-nucleotide polymorphisms (SNPs) were analyzed: rs3834363, rs16909233, rs1054135, rs77878271, rs10808846 and rs8192688. None of the studied gene allele variants were hyper-represented in patients grouped according the presence of metabolic alterations nor were they associated with the FABP4 concentration. The FABP4 gene variants did not determine cIMT differences between the groups. In a multivariate analysis, gender and BMI, but not gene variants, significantly determined plasma FABP4 concentrations. CONCLUSIONS: In clinical settings, the circulating FABP4 levels are determined by the acquired metabolic derangements and not genetic variation.

[Efficacy of the retroperitoneal-assisted laparoscopic pyeloplasty versus the mini posterior lumbotomy approach]. / Eficacia de la pieloplastia asistida por retroperitoneoscopia versus a la realizada por minilumbotomía posterior.

OBJECTIVE: To evaluate the results of the retroperitoneal-assisted laparoscopic pyeloplasty (RALP) versus the mini posterior lumbotomy pyeloplasty (MPLP). MATERIAL AND METHODS: A retrospective study of 77 patients diagnosed with ureteropelvic junction obstruction between 2007 and 2013 was made, analyzing the surgical technique, complications and results. The anteroposterior pelvic diameter of the kidney, the thickness of the renal parenchyma, the renal function and the morphology of the renogram curve were also evaluated and compared. RESULTS: We performed 50 RALP and 21 MPLP. Median age of intervention: 10.85 moths (ICR 86.8) in RALP and 23.30 moths (ICR 54.7) in MPLP. No significant differences were found in surgical time (p>0.05). Double J was left in 90% of the RALP and 52.4% of the MPLP. Median length of incision was 1.5 cm of the RALP and 3.0cm in MPLP(p<0.05). The Median hospital stay was 2.0 days and 3.0 respectively (p<0.05). We found surgical complications (restenosis and urinoma) in 9 patients of the RALP group and 1 in the mini lumbotomy group (p>0,05). The follow-up was performed using ultrasound in an average of 68,04 months of age (range 7.5-186.5) and diuretic renogram in an average of 50,25 months of age (range 6,6-173,8). The above parameters showed improvements in both groups of patients without significant differences. CONCLUSIONS: In our experience, the RALP is a technique with a greater rate of complications than the expected. Moreover, the MPLP, is a technique we consider safe and with adequate aesthetic and functional results.

OBJETIVO: Evaluar la pieloplastia asistida por retroperitoneoscopia, exteriorizando la unión pieloureteral (PAR) versus la pieloplastia por minilumbotomía posterior en ángulo costovertebral (PMLP). MATERIAL Y METODOS: Estudio retrospectivo de 77 pacientes diagnosticados de estenosis pieloureteral (2007-2013), se analizaron técnica, complicaciones y resultados, mediante la valoración del diámetro anteroposterior de la pelvis renal, grosor del parénquima renal, función renal y morfología de la curva del renograma. RESULTADOS: Realizamos 50 PAR y 21 PMLP. Edad mediana de intervención: 10,85 meses [rango intercuartílico (IC) 86,8] en PAR y 23,3 meses (rango IC 54,7) en PMLP. No hubo diferencias significativas en tiempo quirúrgico. Se dejó doble J en 90% de las PAR y en 52,4% de las PMLP. La incisión fue 1,5 cm en la PAR y 3,0 cm de mediana (rango IC 1,0) en la PMLP (p<0,05). La mediana de estancia fue 2,0 días y 3,0 respectivamente (p<0,05). Encontramos complicaciones (reestenosis y urinomas) en 9 pacientes del grupo PAR y en uno en el grupo de minilumbotomía (p>0,05). El seguimiento mediante ecografía en una media de 68,04 meses de edad (rango 7,5-186,5) y renograma diurético en una media de 50,25 meses de edad (rango 6,6-173,8), evidenciaron mejora en los parámetros arriba señalados en ambos grupos de pacientes, sin diferencias significativas. CONCLUSIONES: En nuestra serie, la PAR es un abordaje con un índice de complicaciones mayor al esperado. Por otra parte, la PMLP es un abordaje seguro y con resultados estéticos y funcionales adecuados.

[Endocrine disrupting chemicals exposure and other parental factors in hypospadias and cryptorchidism etiology]. / Exposición a disruptores endocrinos y otros factores paternos en la etiología del hipospadias y la criptorquidia.

AIM OF THE STUDY: To investigate the association between endocrine disrupting chemicals (EDC) exposure and other paternal factors in the etiology of hipospadias and cryptorchidism. METHODS: A case-control study. Cases were infants between 0 and 6 years of age diagnosed with hypospadias or cryptorchidism in our pediatric urology and general pediatric surgery services during a period of 6 months, and controls were infants with the same range of age attending the same services without any urological problem. Several variables were collected by face-to-face interviews with both parents. After data abstraction, we compared the characteristics of both groups using parametric statistical tests. MAIN RESULTS: A total of 180 patients were studied, 90 cases (45 hypospadias/45 cryptorchidism) and 90 controls with a mean age of 2,37 ± 1.50 years [range 0,5-6]. Median of mother´s age was significantly greater in case group (34,40 ± 5,64 versus 31,74 ± 5,05; p= 0,001). Significant differences were observed between cases and controls in regard to maternal occupational exposure to EDC (mainly phthalates), adjusted Odds ratio (OR) was 3.67 [95% confidence interval (CI): 1.28-10.51; p= 0,018] and regarding the paternal occupational exposure to EDC (mainly pesticides and herbicides), adjusted OR was 6.65 [95% CI: 2.60-17.02; p= 0,001]. Increased risk was also observed in smoking fathers and fathers who drink alcohol, adjusted Odds ratio were 2.36 [95% CI: 1.11. CONCLUSIONS: This study represents a little contribution to the possible etiologic factors of hypospadias and cryptorchidism, further studies with higher statistical power would be needed to prove it.

OBJETIVOS: Investigar la asociación entre la exposición a disruptores endocrinos (DE) y otros factores en el desarrollo del hipospadias y la criptorquidia. MATERIAL Y METODS: Estudio de casos y controles. Consideramos como casos a los niños de entre 6 meses y 6 años de edad diagnosticados de hipospadias y/o criptorquidia que acudieron a las consultas de Urología/Cirugía durante un período de estudio de 6 meses y como controles, a los niños con mismo rango de edad que acudieron a las mismas consultas con otros diagnósticos. Recogimos las variables de interés mediante una encuesta epidemiológica y comparamos los resultados obtenidos en cada grupo mediante tests estadísticos paramétricos. RESULTADOS: Estudiamos 180 pacientes, 90 casos (45 hipospadias/45 criptorquidias) y 90 controles, con edad media de 2,60 ± 1,72 años [rango 0,5-6]. Las medias de edad gestacional y peso al nacer fueron menores en el grupo-caso sin objetivarse diferencias significativas. La edad media materna fue significativamente mayor en el grupo-caso (34,40 ± 5,64 versus 31,74 ± 5,05; p= 0,001). Encontramos asociación significativa entre la exposición ocupacional materna a DE (ftalatos principalmente) y el grupo-caso siendo la Odds ratio (OR) de 3,67 (IC 95%: 1,28-10,51; p= 0,018) y también en la paterna (principalmente a pesticidas/herbicidas) con OR= 6,65 (IC 95%: 2,60-17,02; p= 0,001). Encontramos asociación significativa entre el consumo de tabaco y alcohol paternos y el grupo-caso: OR= 2,08 (IC 95%: 1,11-3,87; p= 0,029) y OR= 2,50 (IC 95%: 1,36-4,57; p= 0,003) respectivamente. CONCLUSIONES: Este estudio supone una pequeña aportación respecto a los posibles factores etiológicos del hipospadias y la criptorquidia, y demuestra la necesidad de estudios ulteriores con mayor potencia estadística para aumentar la evidencia científica de nuestros hallazgos.

Circulating FABP4 is a marker of metabolic and cardiovascular risk in SLE patients.

The aim of this study is to determine if circulating fatty acid-binding protein 4 (FABP4) plasma levels are a possible marker of metabolic risk in SLE patients. Circulating levels of adipose FABP4 are associated with adiposity, insulin resistance (IR), metabolic syndrome, diabetes and cardiovascular diseases. Patients affected by systemic lupus erythematosus (SLE) show an accelerated atherosclerosis that cannot be entirely explained by traditional cardiovascular risk factors. Sixty consecutive patients with SLE and 34 non-SLE age-matched controls were recruited for the study. Total plasma lipids and circulating FABP4 were determined. Subclinical atherosclerosis was evaluated by measuring carotid intimae-media thickness (c-IMT) by sonography, and the distribution of lipoprotein subclasses was analysed by nuclear magnetic resonance (NMR) spectroscopy. In the SLE group, FABP4 was associated with IR, atherogenic dyslipidaemia, as measured by NMR, and the presence of subclinical atherosclerosis. In multivariate analyses FABP4 was associated with increased c-IMT independent of the inflammatory state of the patient. In sum, circulating FABP4 is involved in the metabolic disturbances of SLE affecting lipid metabolism and IR, and it could be a biomarker of atherosclerosis in this population.

K+ channels expression in hypertension after arterial injury, and effect of selective Kv1.3 blockade with PAP-1 on intimal hyperplasia formation.

INTRODUCTION: K(+) channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. PURPOSE: To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion . METHODS: Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K(+) channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro. RESULTS: Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4% vs. 70 ± 5% in BPN, p < 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6% vs. 58 ± 20% with vehicle, p < 0.05). CONCLUSIONS: Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.