Detection of anti-HCV antibodies and risk factors in a population with access to public healthcare in Mexico.

INTRODUCTION AND AIM: Timely detection and diagnosis of hepatitis C virus (HCV) involves identifying the population that is predisposed to treatment and prevention, thus limiting complications and preventing infection. The aim of this study was to analyze and describe risk factors associated with anti-HCV antibody detection in a population with access to public healthcare that participated in a national screening program. MATERIAL AND METHODS: An analytic cross-sectional study was conducted that utilized data related to rapid tests carried out between September 2021 and October 2022 in 26 of the 32 states of Mexico. Anti-HCV reactive tests were selected, according to age and sex, for analyzing and comparing possible risk factors through descriptive and inferential statistics. The geographic distribution and density of the screening program at the state and municipal levels was analyzed. RESULTS: There were 75,185 anti-HCV antibody detections, 2,052 reactive tests, and mean participant age was 44.3 years (±15.1). Occupation: 32.3% were employees, 19% were housewives, and 18.2% were healthcare workers. Five out of every 10 cases had no indication of risk factors, but there was a 1.4 and 5-times greater likelihood of anti-HCV detection in men with a history of sharps injury or intravenous psychoactive substance use, compared with women. Regarding place of residence, 80% of the reactive tests were concentrated in the State of Mexico, Mexico City, and Guanajuato. CONCLUSIONS: The evidence herein helps determine the population and risk factors that should be focused on in carrying out the HCV microelimination strategy of continuous screening, diagnosis, medical treatment access, and epidemiologic surveillance.

Immune response in breast cancer surgery. A comparative and prospective study of different anesthetic techniques.

INTRODUCTION: The main reason for high mortality in breast cancer is local recurrence and metastasis, despite surgery as the first therapeutic option. The anesthesia used in the operation room can determine the immune response. METHODS: A prospective, comparative and non- randomised study in patients undergoing breast cancer surgery was conducted in our hospital after obtaining approval from the Hospital's Institutional Review Board. Patients were divided in two groups: Group A received general anesthesia with propofol and opioids. Group B, in addition to general anesthesia, three interfascial blocks (Pec I, Pec II and BRILMA) were performed in all patients. Three blood samples were taken 1) previous anesthetic induction; 2) two hours after the end of the surgery and 3) 24-48 h after surgery. Leukocytes, CD3, CD4, CD8 and Natural Killer cells were determined at each time. RESULTS: 103 patients were included. 59 (group A) received general anesthesia and 54 (group B) general anesthesia and interfascial blocks. Regarding baseline characteristics, age was significantly higher in the group that received general anesthesia and mastectomy was more frequent in the group that received interfascial blocks. We observed after surgery an increase in leukocytes level that returns close to baseline levels. On the other hand, a reduction in the immune response was observed that also returns to the previous level 48 h after surgery. Group A and B get similar results and also subgroups of hormonal receptors (HER+, PR and/or ER+). CONCLUSIONS: Interfascial blocks in chest wall added to general anesthesia in breast cancer surgery has not shown a significant difference in the inflammatory response or immunological depression compared to general anesthesia as the only anesthetic technique. It seems to trend less immunological depression in the interfascial block group.

Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD. MATERIAL AND METHODS: Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon. RESULTS: The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60 min between G1-G3 (p = 0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (p = 0.6) or the number of lymph nodes removed (p = 0.061). The postoperative complication rate was 77% and did not change during the LC (p = 0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (p = 0.217). CONCLUSIONS: The inclusion of junior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC.

Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion. / Análisis del impacto de la curva de aprendizaje de la cistectomía radical asistida por robot con derivación urinaria intracorpórea sobre los resultados perioperatorios.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD. MATERIAL AND METHODS: Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon. RESULTS: The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60minutes between G1-G3 (P=0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (P=0.6) or the number of lymph nodes removed (P=0.061). The postoperative complication rate was 77% and did not change during the LC (P=0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (P=0.217). CONCLUSIONS: The inclusion of júnior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC.

Estrogen-secreting adrenocortical tumor in a postmenopausal woman: a challenging diagnosis.

SUMMARY: Adrenocortical carcinoma (ACC) is a malignant disorder with rapid evolution and severe prognosis in adults and most produce cortisol and androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, especially in women, tend to be larger and have worse prognosis compared with other types of ACCs. We report the case of a 58-year-old woman who presented with bilateral breast enlargement and postmenopausal genital bleeding. She presented high estradiol (818 pg/mL - 25 times above upper normal limit for postmenopausal women) and testosterone (158 ng/dL - 2 times above upper normal limit) levels and no suppression of cortisol after overnight 1 mg dexamethasone test (12.5 µg/dL; normal reference value: < 1.8 µg/dL). The patient had no clinical features of cortisol excess. MRI showed a 12 cm tumor in the right adrenal. Clinical findings of bilateral breast enlargement and postmenopausal genital bleeding with no signs of hypercortisolism associated with hormonal findings of elevated estradiol and testosterone levels would indicate either an ovarian etiology or an adrenal etiology; however, in the context of plasma cortisol levels non-suppressive after dexamethasone test and the confirmation of an adrenal tumor by MRI, the diagnosis of an adrenal tumor with mixed hormonal secretion was made. The patient underwent an open right adrenalectomy and pathological examination revealed an ACC with a Weiss' score of 6. Estradiol and testosterone levels decreased to normal range soon after surgery. She was put on mitotane treatment as adjuvant therapy, but due to side effects, we were unable to up-titrate the dose and she never achieved serum mitotane dosage above the desired 14 µg/mL. The patient remained in good health without any local recurrence or metastasis until 5 years after surgery, when increased levels of estradiol (81 pg/mL - 2.5 times above upper normal limit) and testosterone (170 ng/dL - 2.1 times above upper normal limit) were detected. MRI revealed a retroperitoneal nodule measuring 1.8 × 1.2 cm. The pathological finding confirmed the recurrence of the estrogen-secreting ACC with a Weiss' score of 6. After the second procedure, patient achieved normal estrogen and androgen serum levels and since then she has been followed for 3 years. The overall survival was 8 years after the diagnosis. In conclusion, although extremely rare, a diagnosis of an estrogen-secreting ACC should be considered as an etiology in postmenopausal women presenting with bilateral breast enlargement, genital bleeding and increased pure or prevailing estrogen secretion. LEARNING POINTS: Estrogen-secreting adrenocortical carcinomas are exceedingly rare in adults and account for 1-2% of adrenocortical carcinomas. Estrogen-secreting adrenal tumors can be present in females, but are even more rare, we found few cases described in the literature. In women, they present with precocious puberty or postmenopausal bleeding. Feminization in the context of an adrenal tumor is considered almost pathognomonic of malignancy. Feminizing ACCs tend to be larger and with worse prognosis compared with nonfeminizing ACCs.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others.

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as "transient post-transplant hypercalcemia" (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Educación sexual en las carreras de la salud del Campus Eloísa Díaz de la Universidad de Chile / Evaluation of a general education course on sexuality for university students

Background: Education on human sexuality was instituted in Eloisa Díaz Campus in 1946. From 2018 an online self-learning general education course on sexuality was started. Aim: To know the degree of knowledge about sexuality and the perception about the course of 586 students (42% women) who approved the course. Material and Methods: The Myths and False beliefs and Self-perception on sexuality tests were applied to students at the onset and the end of the course. They also anonymously evaluated the course. Results: In the first assessment, the proportion of correct answers about sexuality and reproduction were 47 and 40% respectively. In the second assessment, 70% of respondents had open criteria about sexuality and 90% rejected traditional criteria. In the anonymous assessment, 95% estimated that the objectives of the course were accomplished. Its quality was considered good or excellent by 95% of respondents. Conclusions: This course was well accepted by students and corrects their knowledge gaps in sexuality. Despite the social unrest during 2019 and the pandemic during 2020, the course was successfully completed by most students.

The COVID-19 pandemic and its repercussions in our interventional radiology unit. / La pandemia COVID-19 y su repercusión en la unidad de radiología intervencionista: nuestra experiencia.

This paper aims to describe our experience in an interventional radiology unit in a hospital in Spain that was severely affected by the COVID-19 pandemic. To this end, we did a prospective observational study of 20 consecutive patients with COVID-19 who underwent 21 interventional radiology procedures between March 13, 2020 and May 11, 2020. We describe the measures taken to reorganize the work and protective measures, as well as the repercussions of the situation on our unit's overall activity and activity in different phases. The COVID-19 pandemic has represented a challenge in our daily work, but learning from our own experience and the recommendations of the Spanish radiological societies (SERVEI and SERAM) has enabled us to adapt successfully. Our activity dropped only 22% compared to the same period in 2019.

Odontogenic Maxillofacial Infections in a High-level Hospital: Orofacial Pain and Related Conditions

ABSTRACT Objective: Odontogenic infection is a common condition in America; the aim of this research was to determine the profile of odontogenic maxillofacial infections and to identify the link between these and the pain felt by patients admitted to the emergency dental service of the Hernân Henriquez Aravena Hospital in Temuco, Chile. Methods: A cross-sectional, double-blind study analysed 49 individuals admitted for emergency dental care. Included were admissions associated with odontogenic infection identified by clinical examination, establishing a relation to pain through a survey. The diagnosis was made clinically using the fascial spaces involved in the infection, presence of self-medication prior to admission, need for surgical treatment and the patient 's systemic conditions. The data were analysed using descriptive statistics, Chi-squared, ANOVA, considering a value of p < 0.05 as significant. Results: The average pain level measured by visual analogue scale (VAS) in emergency admission was 8.1. There was no association between the diagnosis (pulp infection, periodontal infection or pericoronitis) and the VAS (p = 0.078), but there was association between age and the diagnosis (p = 0.022), and the VAS was associated with pain compared to other types of pathologies or traumas (p = 0.011). Conclusion: Odontogenic infection is frequent and linked to age and high-pain values. New public policies should be adopted based on these results. New studies are needed to assess new variables associated with these pathologies.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as "transient post-transplant hypercalcemia" (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients.

BACKGROUND: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. METHODS: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. RESULTS: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). CONCLUSION: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.

ANTECEDENTES: La estratificación de la gravedad de una infección se basa actualmente en la puntuación SOFA (Sequential Organ Failure Assessment), que es difícil de calcular fuera de la unidad de cuidados intensivos. Los biomarcadores podrían ayudar a estratificar la gravedad de la infección en pacientes quirúrgicos. MÉTODOS: Se compararon las concentraciones de 10 biomarcadores que denotan disfunción endotelial, 22 que indican granulopoyesis de emergencia y 6 que expresan la degranulación de neutrófilos en tres grupos de pacientes de tres hospitales españoles (100 con infección, 95 con sepsis y 57 con shock séptico) en las primeras doce horas después del diagnóstico. RESULTADOS: Siete biomarcadores que expresan disfunción endotelial (proadrenomedulina, sindecan-1, trombomodulina, angiopoyetina-2, endocan-1, molécula de adhesión endotelial 1 y E-selectina) mostraron una fuerte asociación con la sepsis en comparación con la infección aislada. La proadrenomedulina presentó el valor más alto de la razón de oportunidades (odds ratio, OR) en el análisis multivariable (OR 11,53, i.c. del 95% 4,15-32,08, P = 0,006) y la mejor área bajo la curva para detectar sepsis (AUC 0,86, i.c. del 95% 0,80-0,91, P < 0,001). En la comparación entre sepsis y shock séptico, los biomarcadores que mostraron la asociación más estrecha con el shock séptico fueron dos biomarcadores de degranulación de neutrófilos (proteinasa-3 y lipocalina-2) (OR 8,09, i.c. del 9% 1,34-48,91, P = 0,028; OR 6.62, i.c. del 95% 2,47-17,77, P = 0,002), pero la lipocalina-2 presentó la mejor AUC (0,81, i.c. del 95% 0,73-0,90, P < 0,001). CONCLUSIÓN: la proadrenomedulina y la lipocalina-2 podrían representar alternativas a la puntuación SOFA para detectar sepsis y shock séptico en pacientes quirúrgicos con infección.

Tromboprofilaxis en pacientes médicos y quirúrgicos: resultados de un estudio multicéntrico realizado en hospitales de la Ciudad de México / Thromboprophylaxis in medical and surgical patients: results of a multicenter study in hospitals of Mexico City

Resumen: ANTECEDENTES: la enfermedad tromboembólica venosa es una complicación que puede manifestarse durante o después de la hospitalización. Existen pocos antecedentes en nuestro país que evalúan el comportamiento médico en este tema. OBJETIVO: conocer la prescripción relacionada con el tipo, duración y posibles causas de la omisión de tromboprofilaxis en pacientes hospitalizados. MATERIAL Y MÉTODO: estudio descriptivo, transversal y no probabilístico en el que de septiembre a noviembre de 2016 se evaluaron médicos de Medicina Interna, Cirugía General, Terapia Intensiva y Urgencias. Se recolectaron datos por cuestionario y presentación de resultados a través de estadística descriptiva. También se evaluó la duración de la prescripción y la dosis administrada. RESULTADOS: se encuestaron 556 médicos adscritos, 14 jefes de servicio y 234 residentes total: 804 de siete hospitales de la Ciudad de México pertenecientes al sistema de salud. El 30% refirió que su hospital cuenta con un programa de tromboprofilaxis; 97.7% la considera segura y 1.2%, riesgosa. El 96% respondió que prescribe tromboprofilaxis en sus pacientes; 592 74% utilizan alguna escala de previsión clínica de enfermedad tromboembólica venosa. El 71% recomienda heparina de bajo peso molecular para tromboprofilaxis y 0.74% administra anticoagulantes orales de nueva generación. CONCLUSIONES: la enfermedad tromboembólica venosa es potencialmente prevenible; sin embargo, la prescripción muestra oportunidades de mejoría en aspectos de farmacología.

Abstract: BACKGROUND: Venous thromboembolic disease VTE is a complication that may occur during or after hospitalization. There are few antecedents in our country that evaluate the medical behavior in this subject. OBJECTIVE: To know the prescription related to type, duration and possible causes for omission of thromboprophylaxis in hospitalized patients. MATERIAL AND METHOD: A descriptive, transversal and non-probabilistic study was done, in which from September to November 2016 physicians of Internal Medicine, General Surgery, Intensive Care and Urgency were evaluated through a data collection by questionnaire and presentation of results through descriptive statistics. We also evaluated duration of prescription and dose administered. RESULTS: A total of 556 seconded physicians, 14 service heads, and 234 residents 804 in total were surveyed in seven hospitals in Mexico City belonging to the health system. Thirty percent reported that their hospital has a thromboprophylaxis program; 97.7% consider it safe and 1.2% risky; 96% responded that they prescribe thromboprophylaxis in their patients; 592 73.6% used some clinical prediction scale for VTE; 71% recommended low molecular weight heparin for thrombo prophylaxis and 0.74% administered new generation oral anticoagulants. CONCLUSIONS: Venous thromboembolic disease is potentially preventable; however, prescription shows opportunities for improvement in aspects of pharmacology.

Disturbed testicular expression of the estrogen-metabolizing enzymes CYP1A1 and COMT in infertile men with primary spermatogenic failure: possible negative implications on Sertoli cells.

Estradiol (E2 ) is normally metabolized to hydroxyestradiols and methoxyestradiols by CYP1A1, CYP1B1 and COMT. However, an altered production of these metabolites by a disturbed expression of these enzymes is associated with reproductive and non-reproductive pathologies. In vitro studies suggest that increased hydroxyestradiols and methoxyestradiols intratesticular generation is related to male infertility, but no studies have explored whether infertile men have a disturbed testicular expression of the enzymes that generate these E2 metabolites. The aim of this study was to assess CYP1A1, CYP1B1 and COMT testicular expression at mRNA and protein level in men with spermatogenic impairment. Seventeen men with primary spermatogenic failure (13 with Sertoli cell-only syndrome and four with maturation arrest) and nine controls with normal spermatogenesis were subjected to testicular biopsy. mRNA was quantified using real-time RT-PCR and protein expression was evaluated using western blot and immunohistochemistry followed by integrated optic density analysis. Besides, the effects of hydroxyestradiols and methoxyestradiols on testosterone-induced transcriptional activity were evaluated in TM4 cells using a luciferase reporter assay system. Our results show that patients with Sertoli cell-only syndrome had significantly elevated COMT expression at the mRNA level, higher COMT immunoreactivity in their seminiferous tubules and increased protein expression of the soluble COMT isoform (S-COMT), whereas patients with maturation arrest had significantly elevated CYP1A1 mRNA levels and higher CYP1A1 immunoreactivity in interstitial space. Finally, 2-hydroxyestradiol decreased testosterone-induced transcriptional activity in Sertoli cells in vitro. In conclusion, male infertility is related to disturbed testicular expression of the enzymes responsible for producing hydroxyestradiols and/or methoxyestradiols. If these changes are related with increased intratesticular hydroxyestradiols and methoxyestradiols concentrations, they could elicit an impaired Sertoli cell function. Our results suggest CYP1A1 and COMT as new potential targets in treating male infertility.

Primary lymphocytic lymphoma of lacrimal gland. / Linfoma linfocítico primario de glándula lagrimal.

CASE REPORT: We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. DISCUSSION: Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

2-hydroxyoestradiol and 2-methoxyoestradiol, two endogenous oestradiol metabolites, induce DNA fragmentation in Sertoli cells.

Elevated intratesticular levels of hydroxyoestradiols and methoxyoestradiols, two classes of endogenous oestradiol metabolites, have been associated with male infertility. The aim of this study was to explore the effects of 2-hydroxyoestradiol (2OHE2 ), 4-hydroxyoestradiol (4OHE2 ), 2-methoxyoestradiol (2ME2 ) and 4-methoxyoestradiol (4ME2 ) on Sertoli cell viability. For this, TM4 cells were incubated with different concentrations of these metabolites for 24 h to then evaluate the viability and DNA integrity by MTS and TUNEL assay respectively. The participation of classical oestrogen receptors and the involvement of oxidative stress and apoptotic mechanisms were also evaluated co-incubating TM4 cells with these estradiol metabolites and with the drugs ICI182780, N-acetylcysteine and Z-VAD-FMK respectively. Only high concentrations of 2OHE2 and 2ME2 decreased cell viability inducing DNA fragmentation. In addition, ICI182780 did not block the effect of 2OHE2 and 2ME2 , while N-Acetylcysteine and Z-VAD-FMK only blocked the effect of 2OHE2 . Moreover, 2OHE2 but not 2ME2 induced PARP and caspase-3 cleavage. Finally, lower 2OHE2 and 2ME2 concentrations (0.01-0.1-1.0 µmol l-1 ) decreased Sertoli cell viability 48 h post-treatment. Our results support the hypothesis that elevated intratesticular 2OHE2 or 2ME2 concentrations could be related to male infertility since 2OHE2 by apoptosis and 2ME2 by undetermined mechanisms induce DNA fragmentation in Sertoli cells.

Diferencias de género en la calidad de vida relacionada con la salud en adolescentes escolarizados chilenos / Gender differences in health-related quality of life of Chilean adolescent students

Background: Health-related quality of life (HRQOL) refers to individuals' perception of their subjective well-being, considering various aspects of their life and the impact on their health. Aim: To analyze gender differences in the HRQOL of adolescent students in Chile, by age, type of school attended, and area of residence. Material and Methods: Analytical cross-sectional study conducted in a population of 5th and 12th grade students attending municipal, subsidized and private schools in 11 regions of the country. HRQOL was assessed with the KIDSCREEN-52, an instrument that has been previously adapted and validated in Chile. The database obtained from that adaption and validation process was analyzed. Results: In total, 7,910 students (median age 14 years, 53% female) completed the questionnaire. Compared to males, females had lower HRQOL scores in most of the KIDSCREEN-52 dimensions. However, males were more likely to have lower scores in the “Peers and Social Support” and “School Environment” dimensions. These differences remained valid when the sample was stratified by age, type of school, and area of residence were analyzed. Conclusions: This study supports the existence of inequalities in the self-perceived HRQOL of Chilean adolescent students. The existing differences are not only related to gender but are also evident when stratifying by type of school attended.

Nitric oxide stress and activation of AMP-activated protein kinase impair ß-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.

The sarcoendoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) concentration gradient between the cytosol and ER lumen in the pancreatic ß-cell, and the integrity of this gradient has a central role in regulated insulin production and secretion, maintenance of ER function and ß-cell survival. We have previously demonstrated loss of ß-cell SERCA2b expression under diabetic conditions. To define the mechanisms underlying this, INS-1 cells and rat islets were treated with the proinflammatory cytokine interleukin-1ß (IL-1ß) combined with or without cycloheximide or actinomycin D. IL-1ß treatment led to increased inducible nitric oxide synthase (iNOS) gene and protein expression, which occurred concurrently with the activation of AMP-activated protein kinase (AMPK). IL-1ß led to decreased SERCA2b mRNA and protein expression, whereas time-course experiments revealed a reduction in protein half-life with no change in mRNA stability. Moreover, SERCA2b protein but not mRNA levels were rescued by treatment with the NOS inhibitor l-NMMA (NG-monomethyl L-arginine), whereas the NO donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) and the AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) recapitulated the effects of IL-1ß on SERCA2b protein stability. Similarly, IL-1ß-induced reductions in SERCA2b expression were rescued by pharmacological inhibition of AMPK with compound C or by transduction of a dominant-negative form of AMPK, whereas ß-cell death was prevented in parallel. Finally, to determine a functional relationship between NO and AMPK signaling and SERCA2b activity, fura-2/AM (fura-2-acetoxymethylester) Ca(2+) imaging experiments were performed in INS-1 cells. Consistent with observed changes in SERCA2b expression, IL-1ß, SNAP and AICAR increased cytosolic Ca(2+) and decreased ER Ca(2+) levels, suggesting congruent modulation of SERCA activity under these conditions. In aggregate, these results show that SERCA2b protein stability is decreased under inflammatory conditions through NO- and AMPK-dependent pathways and provide novel insight into pathways leading to altered ß-cell calcium homeostasis and reduced ß-cell survival in diabetes.

Enfermedad de Rosai-Dorfman mamario / Mammary Rosai Dorfman disease

Background: Rosai Dorfman disease is uncommon and consists in a benign fibrous and hematopoietic tissue proliferation, usually located in the head or neck. It is self-limited and the treatment is the surgical excision of the lesion. Case Report: We report a 69 years old woman consulting for a palpable right breast nodule with a mammography and mammary ultrasound informed as BIRADS 4 and 5, respectively. A core biopsy was informed as a mammary Rosai Dorfman disease. Two years later, due to a lesion growth, the patient was subjected to a partial mastectomy. The pathological study of the surgical piece confirmed the diagnosis of the core biopsy. This disease may resemble a malignant disease and the clue for its diagnosis is the pathological study.

Introducción: La enfermedad de Rosai Dorfman es una entidad infrecuente, que consiste en la proliferación benigna del tejido fibroso y hematopoyético ubicado generalmente en cabeza y cuello. Se trata de una enfermedad benigna, autolimitada, cuyo tratamiento generalmente se limita a la resección quirúrgica, con elevada tasa de recidiva. Objetivo: Exposición de un caso de Enfermedad de Rosai Dorfman mamario, inicial-mente sugerente de patología maligna. caso clínico: Mujer 69 años derivada de atención primaria por nódulo palpable en mama derecha, mamografía y ecografía mamaria BIRADS 4 y 5, respectivamente. Biopsia Core informa Enfermedad de Rosai Dorfman mamaria. A los dos años de diagnóstico se objetiva lesión de mayor tamaño. Se realizó mastectomía parcial con biopsia de pieza quirúrgica compatible con diagnóstico de Biopsia Core previa. Discusión: La similitud clínica de esta enfermedad con patologías malignas mamarias, asociado a su baja prevalencia, dificultan la pesquisa de casos como el expuesto. En los estudios de imágenes raramente se sospecha. La clave del diagnóstico son los hallazgos histológicos en el que característicamente se observa emperipolesis con tinciones inmunohistoquímicas positivas para S 100 y negativo para CD 1. Dado que es una enfermedad benigna y autolimitada su tratamiento generalmente se limita a la resección quirúrgica. Este permite extirpar el tumor en estudio, realizar el diagnóstico, y aliviar la sintomatología producida por el efecto masa de la lesión. A pesar de lo anterior la recidiva es alta, por lo que el seguimiento debe ser a largo plazo.