The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin.

BACKGROUND: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown. METHODS: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models. RESULTS: MiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats. CONCLUSIONS: Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity. SIGNIFICANCE STATEMENT: Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.

Resultados de una encuesta nacional sobre el manejo de los pacientes diagnosticados de diverticulitis aguda no complicada / Results of a national survey about the management of patients with acute uncomplicated diverticulitis

Introducción: El manejo de los pacientes diagnosticados de diverticulitis aguda no complicada ha evolucionado en los últimos años, y según diversas guías clínicas internacionales actuales, el tratamiento ambulatorio y sin antibioterapia puede ser utilizado en pacientes seleccionados. El objetivo de este estudio es evaluar la adhesión de los distintos centros nacionales a estas y otras recomendaciones en esta enfermedad. Métodos: Se realizó una encuesta online a nivel nacional que se dio a conocer a través de diversas aplicaciones informáticas y se analizaron estadísticamente los resultados obtenidos. Resultados: Participaron 104 cirujanos, representando 69 centros hospitalarios nacionales. En el 82,6% de los centros, se realiza manejo ambulatorio de los pacientes diagnosticados de diverticulitis aguda no complicada. El 23,2% de los centros tiene implantado un protocolo de tratamiento sin antibioterapia en pacientes seleccionados, mientras que en los centros que no siguen estas recomendaciones, las razones principales son las dificultades logísticas para su desarrollo (49,3%) y la ausencia de evidencia actual para ello (44,8%). Se han encontrado diferencias estadísticamente significativas al comparar la implantación de dichos protocolos entre centros con unidades acreditadas avanzadas y aquellas que no, con mayores tasas de manejo ambulatorio y sin antibioterapia en los centros acreditados avanzados (p≤0,05). Conclusiones: A pesar de ser una enfermedad muy frecuente, existe mucha heterogeneidad en su tratamiento a nivel nacional, por lo que sería recomendable la unificación de criterios diagnósticos y de tratamiento mediante la colaboración de las sociedades científicas y la simplificación de la puesta en marcha de protocolos hospitalarios.(AU)

Introduction: Management of patients diagnosed of acute uncomplicated diverticulitis has evolved lately and according to the latest guidelines, outpatient treatment and management without antibiotherapy may be used in selected patients. The aim of this study is to evaluate the adhesion among national centres to these and others recommendations related to this pathology. Methods: An online national survey, that has been broadcast by several applications, was performed. The results obtained were statistically analysed. Results: A total of 104 surgeons participated, representing 69 national hospitals. Of those, in 82.6% of the centers, outpatient management is performed for acute uncomplicated diverticulitis. 23.2% of the hospitals have a protocol stablished for treatment without antibiotherapy in selected patients. Centers that do not follow these protocols allege that the mean reasons are the logistic difficulties to set them up (49.3%) and the lack of current evidence for it (44.8%). Significative statistical differences have been found when comparing the establishment of such protocols between centers with advanced accredited units and those who are not, with higher rates of outpatient management and treatment without antibiotics in accredited units (P≤.05). Conclusions: In spite that this a very common disease, there is a huge national heterogeneity in its treatment. This is why it would adviseable to unify diagnostic and treatment criteria by the collaboration of scientific societies and the simplification of the development of hospitalary protocols.(AU)

Results of a national survey about the management of patients with acute uncomplicated diverticulitis.

INTRODUCTION: Management of patients diagnosed of acute uncomplicated diverticulitis has evolved lately and according to the latest guidelines, outpatient treatment and management without antibiotherapy may be used in selected patients. The aim of this study is to evaluate the adhesión among national centres to these and others recommendations related to this pathology. METHODS: An online national survey, that has been broadcast by several applications, was performed. The results obtained were statistically analysed. RESULTS: A total of 104 surgeons participated, representing 69 national hospitals. Of those, in 82.6% of the centres, outpatient management is performed for acute uncomplicated diverticulitis. 23.2% of the hospitals have a protocol stablished for treatment without antibiotherapy in selected patients. Centres that do not follow these protocols allege that the mean reasons are the logistic difficulties to set them up (49.3%) and the lack of current evidence for it (44.8%). Significative statistical differences have been found when comparing the establishment of such protocols between centres with advanced accredited units and those who are not, with higher rates of outpatient management and treatment without antibiotics in accredited units (p ≤ .05). CONCLUSIONS: In spite that this a very common disease, there is a huge national heterogeneity in its treatment. This is why it would adviseable to unify diagnostic and treatment criteria by the collaboration of scientific societies and the simplification of the development of hospitalary protocols.

FiLaC procedure for highly selected anal fistula patients: indications,safety and efficacy from an observational study at a tertiary referral center / Procedimiento FiLaC para pacientes con fístula anal altamente seleccionados: indicaciones, seguridad y eficacia de un estudio observacional en un centro de referencia terciario

Background: the ideal clinical profile of patients or fistula features for fistula laser closure (FiLaC®) technique remain to be established. The aim of this study was to analyze clinical outcomes and the safety profile of FiLaC® in search for an ideal setting for this technique. Methods: a retrospective observational study was performed from a prospective database including all consecutive patients who underwent surgery for anal fistula (AF) with FiLaC® in the coloproctology unit of a tertiary referral center, between October 2015 and December 2021. The FiLaC® procedure was offered to AF patients who were considered to be at risk of fecal incontinence. Fistulas were described according to Parks’ classification and categorized as complex or simple according to the American Gastroenterological Association (AGA) guidelines. Healing was defined by the closure of the internal and external openings for at least six months. Predictive factors of AF healing were investigated. Results: a total of 36 patients were included, with a mean age of 48 ± 13.9 years. Twenty patients (55.6 %) were male and 13 patients (36 %) had Crohn’s disease (CD). Fourteen patients (38.8 %) had a complex fistula. The primary and secondary healing rates were 55.6 % and 91.7 %, respectively, during a median follow-up time of 12 months (IQR 7-29). No fecal continence impairment was registered in any case. The proportion of patients with primary healing was significantly higher in CD patients (76.9 % vs 43.5 %, p = 0.048). Conclusions: FiLaC® is a sphincter-preserving procedure with an excellent safety profile and reasonable success rate despite of the strict patient selection. This technique may be attractive for patients with CD due to its higher primary healing rate.(AU)

Integrating clinical research in an operative screening and diagnostic breast imaging department: First experience, results and perspectives using microwave imaging.

Rationale and objectives: Clinical research is crucial for evaluating new medical procedures and devices. It is important for healthcare units and hospitals to minimize the disruptions caused by conducting clinical studies; however, complex clinical pathways require dedicated recruitment and study designs.This work presents the effective introduction of novel microwave breast imaging (MBI), via MammoWave apparatus, into the clinical routine of an operative screening and diagnostic breast imaging department for conducting a multicentric clinical study. Materials and methods: Microwave breast imaging, using MammoWave apparatus, was performed on volunteers coming from different clinical pathways. Clinical data, comprising demographics and conventional radiologic reports (used as reference standard), was collected; a satisfaction questionnaire was filled by every volunteer. Microwave images were analyzed by an automatic clinical decision support system, which quantified their corresponding features to discriminate between breasts with no relevant radiological findings (NF) and breasts with described findings (WF). Results: Conventional breast imaging (DBT, US, MRI) and MBI were performed and adapted to assure best clinical practices and optimum pathways. 180 volunteers, both symptomatic and asymptomatic, were enrolled in the study. After microwave images' quality assessment, 48 NF (15 dense) and 169 WF (88 dense) breasts were used for the prospective study; 48 (18 dense) breasts suffered from a histology-confirmed carcinoma. An overall sensitivity of 85.8 % in breasts lesions' detection was achieved by the microwave imaging apparatus. Conclusion: An optimum recruitment strategy was implemented to assess MBI. Future trials may show the clinical usefulness of microwave imaging, which may play an important role in breast screening.

FiLaC® procedure for highly selected anal fistula patients: indications, safety and efficacy from an observational study at a tertiary referral center.

BACKGROUND: the ideal clinical profile of patients or fistula features for fistula laser closure (FiLaC®) technique remain to be established. The aim of this study was to analyze clinical outcomes and the safety profile of FiLaC® in search for an ideal setting for this technique. METHODS: a retrospective observational study was performed from a prospective database including all consecutive patients who underwent surgery for anal fistula (AF) with FiLaC® in the coloproctology unit of a tertiary referral center, between October 2015 and December 2021. The FiLaC® procedure was offered to AF patients who were considered to be at risk of fecal incontinence. Fistulas were described according to Parks' classification and categorized as complex or simple according to the American Gastroenterological Association (AGA) guidelines. Healing was defined by the closure of the internal and external openings for at least six months. Predictive factors of AF healing were investigated. RESULTS: a total of 36 patients were included, with a mean age of 48 ± 13.9 years. Twenty patients (55.6 %) were male and 13 patients (36 %) had Crohn's disease (CD). Fourteen patients (38.8 %) had a complex fistula. The primary and secondary healing rates were 55.6 % and 91.7 %, respectively, during a median follow-up time of 12 months (IQR 7-29). No fecal continence impairment was registered in any case. The proportion of patients with primary healing was significantly higher in CD patients (76.9 % vs 43.5 %, p = 0.048). CONCLUSIONS: FiLaC® is a sphincter-preserving procedure with an excellent safety profile and reasonable success rate despite of the strict patient selection. This technique may be attractive for patients with CD due to its higher primary healing rate.

Metástasis orbitaria solitaria como presentación inicial de cáncer de mama / Isolated orbital metastasis as an initial presentation of a breast cancer

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Hamartoma quístico retrorrectal: presentación de 4 casos / Tailgut cysts: presentation of four cases

No disponible

Disección espontánea de arteria mesentérica superior / Spontaneous dissection of the superior mesenteric artery

No disponible

An unusual enterolith ileus.

The duodenum is an uncommon location of diverticula in the digestive tract, and they are often asymptomatic. Formation of an enterolith inside diverticula has been previously described, although it is a rare condition. In this context, intestinal obstruction due to distal migration of foreign bodies is extremely rare. We report a case of an 86-year-old woman with obstructive symptoms due to a jejunal foreign body that had migrated from a duodenal diverticulum. An emergency laparotomy was performed to extract a phytobezoar. Enterolith ileus secondary to duodenal diverticula is an exceptional entity. Diagnosis and management are usually delayed because of a non-specific presentation, and early surgical exploration is required for bowel disimpaction. This condition should be considered in elderly patients with prolonged immobilization or neurodegenerative diseases.

An unusual enterolith ileus

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Meiotic segregation analyses of reciprocal translocations in spermatozoa and embryos: no support for predictive value regarding PGD outcome.

Translocation heterozygotes have an increased risk of producing gametes with unbalanced chromosome content. This often leads to reproductive problems such as infertility, repeated miscarriages or birth of an affected child. To increase the chances of having a healthy live-born child, translocation heterozygotes often opt for preimplantation genetic diagnosis (PGD). The aim of this study was to investigate whether there is a correlation between chromosome segregation in spermatozoa from translocation heterozygotes and the number of balanced embryos produced during PGD that may be used to predict the PGD outcome. Ten male reciprocal translocation heterozygotes that went through PGD at a Stockholm PGD centre were included. We analysed 1000 spermatozoa from each patient and between 3 and 29 embryos from the total of PGD cycles that the couples went through. Fluorescence in-situ hybridization (FISH) analysis of spermatozoa and embryos was performed with the same DNA probes. We found that the proportion of balanced spermatozoa was much higher than the proportion of balanced embryos during PGD. Our results indicate that a sperm FISH analysis prior to PGD is not a reliable predictor of the PGD outcome. PGD is a valuable reproductive alternative for translocation heterozygotes with reproductive problems and should be offered to these couples.

Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 2A Syndrome.

Parathyroid carcinoma is a very rare malignancy. It has been associated with hyperparathyroidism-jaw tumour syndrome, familial isolated primary hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1) and 2A (MEN-2A) syndromes. We report a 54-year-old man with a MEN-2A which presents with a nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma have been reported in the literature associated with this syndrome.