Outcome of cutaneous squamous cell carcinoma with microscopic residual disease after surgery and usefulness of postoperative radiotherapy: a retrospective cohort study.

BACKGROUND: Microscopic residual disease (MRD) after surgery can be a challenging situation in cutaneous squamous cell carcinoma (CSCC) and there is a lack of evidence concerning its management. OBJECTIVE: To evaluate the prognosis of CSCC with MRD and the usefulness of postoperative radiotherapy (PORT) in CSCC with MRD. METHODS: Retrospective cohort study of CSCC with MRD through a 10-year period (2010-2019) (n = 244). Disease-free survival and event-free survival were assessed using R (v.3.4.1), considering competing risks. Evaluated outcomes were local recurrence (LR), nodal metastases (NMs), and disease-specific death (DSD). RESULTS: Median age was 88y (IQR: 10.5). A total of 145 (59.43%) were men and 69 (28.28%) were immunosuppressed. Median tumour diameter and thickness were 19 and 6.4 mm (IQR 11 and 5.5 mm). Patients treated by re-excision had a relapse rate of 4.3% compared with 11.30% and 29.71% in those who received PORT and observation (P = 0.045). The use of PORT was associated with a lower risk of LR compared with observation (HR = 0.206 [0.049-0.859], P = 0.030), but not with a lower risk of NMs or DSDs. In the multivariable models, PORT was again associated with a lower risk of LR than observation (HR = 0.167 [0.039-0.708], P = 0.014), but not with lower risk of metastasis and death. CONCLUSIONS: We always should try to obtain clear margins after surgery. PORT improves local control in CSCC with MRD, but when administered to the tumour bed, it does not reduce the risk of NM and DSD.

Role of ghrelin isoforms in the mitigation of hepatic inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress after bariatric surgery in rats.

BACKGROUND/OBJECTIVES: Bariatric surgery improves nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain elusive. We evaluated the potential role of ghrelin isoforms in the amelioration of hepatic inflammation after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). SUBJECTS/METHODS: Plasma ghrelin isoforms were measured in male Wistar rats (n = 129) subjected to surgical (sham operation, sleeve gastrectomy, or RYGB) or dietary interventions [fed ad libitum a normal (ND) or a high-fat diet (HFD) or pair-fed diet]. The effect of acylated and desacyl ghrelin on markers of inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in primary rat hepatocytes under palmitate-induced lipotoxic conditions was assessed. RESULTS: Plasma desacyl ghrelin was decreased after sleeve gastrectomy and RYGB, whereas the acylated/desacyl ghrelin ratio was augmented. Both surgeries diminished obesity-associated hepatic steatosis, CD68+- and apoptotic cells, proinflammatory JNK activation, and Crp, Tnf, and Il6 transcripts. Moreover, a postsurgical amelioration in the mitochondrial DNA content, oxidative phosphorylation (OXPHOS) complexes I and II, and ER stress markers was observed. Specifically, following bariatric surgery GRP78, spliced XBP-1, ATF4, and CHOP levels were reduced, as were phosphorylated eIF2α. Interestingly, acylated and desacyl ghrelin inhibited steatosis and inflammation of palmitate-treated hepatocytes in parallel to an upregulation of OXPHOS complexes II, III, and V, and a downregulation of ER stress transducers IRE1α, PERK, ATF6, their downstream effectors, ATF4 and CHOP, as well as chaperone GRP78. CONCLUSIONS: Our data suggest that the increased relative acylated ghrelin levels after bariatric surgery might contribute to mitigate obesity-associated hepatic inflammation, mitochondrial dysfunction, and ER stress.

Frecuencia y factores asociados a la histerectomía obstétrica en un hospital de segundo nivel en México / Frequency and factors associated with obstetric hysterectomy in a second level hospital in México

INTRODUCCION La histerectomía obstétrica es procedimiento de urgencia para resolver una situación grave, su incidencia es de 5 a 15 por cada 1000 eventos obstétricos OBJETIVO GENERAL Determinar la frecuencia y factores asociados a la histerectomía obstétrica en un hospital de segundo nivel en México. METODOLOGIA Estudio descriptivo, transversal y retrospectivo en el periodo de Enero de 2014 a Diciembre del 2016, se incluyeron todos los casos de histerectomía posterior a un evento obstétrico, se estudiaron: edad, paridad, vía de interrupción del embarazo, antecedente de cesárea previa, indicaciones y complicaciones de la histerectomía, ingreso al servicio de terapia intensiva y mortalidad, el análisis se realizó con estadística descriptiva. RESULTADOS Durante el periodo de estudio, se atendieron 37 308 eventos obstétricos, efectuándose histerectomía obstétrica a 153 pacientes que representan el 0.57%, es decir, una HO por cada 243 embarazos. La edad promedio de quienes se les efectuó la histerectomía fue de 34 años de edad, siendo más frecuente en el grupo de mayores de 35 años, que habían tenido dos o tres embarazos previos. El antecedente de cesárea previa fue del 69.2%. La vía de interrupción del embarazo actual fue de cesárea en el 72.1%. La principal indicación fue la atonía uterina en 51 casos (33.3%). La complicación más frecuente fue la anemia aguda en el 83%. Hubo 1 muerte materna (0.6%). CONCLUSIONES La Histerectomía obstétrica es una cirugía de urgencia, por lo que se deben de identificar durante el control prenatal los factores asociados a las principales indicaciones de esta complicación.

INTRODUCTION Obstetric Hysterectomy (OH) is an emergency procedure to solve a life threatening condition, and its incidence is 5 to 15 per 1000 obstetric events. GENERAL OBJETIVE To determine the frequency and factors related with obstetric hysterectomy at a secondary hospital in Mexico. METHODOLOGY Descriptive, cross-sectional and retrospective study from January 2014 to December 2016 including all hysterectomy cases due to an obstetric event. Factors such as Age, number of deliveries, abortions, and previous cesarean sections, admission to the Intensive care unit, surgical indications, complications and mortality because of hysterectomy were analyzed thru descriptive statistics. RESULTS 37 308 obstetric events were registered and 153 were treated with Obstetric Hysterectomy representing 0.57% of the total, meaning one OH per every 243 pregnancies. The average age of those who had a hysterectomy was 28.5 years, and the procedure had its peak at the group of age older than 35 years who had had two or more pregnancies. The history of previous cesarean section was 39.2%. In 72.1% the pregnancy was terminated with a cesarean section. The main indication for hysterectomy was Uterine Atony in 33.3% (51 cases). The most frequent complication was acute anemia in 83%. There was a maternal death (0.6%). CONCLUSIONS Obstetric Hysterectomy is an emergency surgery, there are related factors that must be identified during the prenatal control to avoid this complication.

Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic ß-cell function after sleeve gastrectomy in obese rats.

BACKGROUND/OBJECTIVES: Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in ß-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats. SUBJECTS/METHODS: Male Wistar obese rats (n=125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F ß-cells. RESULTS: Sleeve gastrectomy reduced pancreatic ß-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F ß-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RIN-m5F ß-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated ß-cells. CONCLUSIONS: AQP7 upregulation in ß-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.

Crosstalk between adipokines and myokines in fat browning.

Skeletal muscle is the largest organ determining whole-body insulin sensitivity and metabolic homoeostasis. Adaptive changes of skeletal muscle in response to physical activity include adjustments in the production and secretion of muscle-derived bioactive factors, known as myokines, such as myostatin, IL-4, IL-6, IL-7 and IL-15, myonectin, follistatin-like 1 or leukaemia inhibitory factor. These myokines not only act locally in the muscle in an autocrine/paracrine manner, but also are released to the bloodstream as endocrine factors to regulate physiological processes in other tissues. Irisin, derived from the cleavage of FNDC5 protein, constitutes a myokine that induces myogenesis and fat browning (switch of white adipocytes to brown fat-like cells) together with a concomitant increase in energy expenditure. Besides being a target for irisin actions, the adipose tissue also constitutes a production site of FNDC5. Interestingly, irisin secretion from subcutaneous and visceral fat depots is decreased by long-term exercise training and fasting, suggesting a discordant regulation of FNDC5/irisin in skeletal muscle and adipose tissue. Accordingly, our group has recently reported that the adipokine leptin differentially regulates FNDC5/irisin expression in skeletal muscle and fat, confirming the crosstalk between both tissues. Moreover, irisin secretion and function are regulated by other myokines, such as follistatin or myostatin, as well as by other adipokines, including fibroblast growth factor 21 and leptin. Taken together, myokines have emerged as novel molecular mediators of fat browning and their activity can be modulated by adipokines, confirming the crosstalk between skeletal muscle and adipose tissue to regulate thermogenesis and energy expenditure.

Factores biopsicosociales asociados a la disfunción sexual femenina en una población mexicana / Biopsychosocial factors associated with female sexual dysfunction in a mexican population

Objetivo: Determinar los factores biopsicosociales asociados a la disfunción sexual femenina en una población mexicana. Métodos: Estudio comparativo en mujeres que acudieron como acompañantes a una Unidad de Medicina Familiar de Querétaro, México. Se aplicaron las encuestas de Laumman, Chávez y Velazco, Faces III, y Grajales para valorar sexualidad, funcionalidad conyugal, funcionalidad familiar y estado de la autoestima. Los resultados fueron analizados con Odds Ratios, Chi cuadrado y t de Student. Resultados: De 110 mujeres entrevistadas, 65 (59 por ciento) refirieron alguna disfunción sexual y 45 (41 por ciento) lo negaron. Se formaron aleatoriamente dos grupos de 44 mujeres: con y sin disfunción sexual. Los factores que se asociaron significativamente a las alteraciones sexuales fueron: edad mayor a 40 años, laborar fuera del hogar, presencia de obesidad y/o sobrepeso, hipertensión arterial, diabetes mellitus, histerectomía previa, maternidad, disfuncionalidad conyugal, autoestima alta, depresión leve a severa, familia disfuncional, estrato socioeconómico bajo. Las alteraciones sexuales más frecuentes fueron: disminución en el deseo sexual (34,1 por ciento), disfunción eréctil de la pareja (22,7 por ciento), dispareunia y falta de excitación (20,5 por ciento), sexo referido como desagradable e incapacidad para llegar al orgasmo (13,6 por ciento), ansiedad por el desempeño sexual (6,8 por ciento) y eyaculación precoz (4,5 por ciento). Conclusiones: Es importante identificar los factores que afectan la sexualidad femenina para ofrecer un manejo multidisciplinario y prevenir implicaciones a nivel del entorno familiar y conyugal.

Objective: To determine the biopsychosocial factors associated with female sexual dysfunction in a Mexican population. Methods: A comparative study in women who were attended at a Family Medicine Unit of Queretaro, Mexico. Surveys of Laumman, Chavez and Velazco, Faces III, and Grajales, were applied to assess sexuality, marital functionality, familiar functionality and state self-esteem. The results were analyzed with Odds Ratios, chi-square and Student t test. Results: Of 110 women interviewed, 65 (59 percent) reported sexual dysfunction and 45 (41 percent) denied. They formed two groups randomly from 44 women with and without sexual dysfunction. Factors that were significantly associated with sexual disorders were: age greater than 40 years, labor outside the home, presence of obesity and/or overweight, hypertension, diabetes mellitus, prior hysterectomy, maternity, marital dysfunction, high self-esteem, mild to severe depression, dysfunctional family, low socioeconomic status. The most common sexual dysfunction were: decrease in sexual desire (34.1 percent), erectile dysfunction couples (22.7 percent), dyspareunia and lack of arousal (20.5 percent), referred to as unpleasant sex and inability to reach orgasm 13.6 percent) sexual performance anxiety (6.8 percent) and premature ejaculation (4.5 percent). Conclusions: It is important to identify the factors affecting female sexuality to offer multidisciplinary management and prevention implications at the level of family and marital environment.

Short- and long-term changes in gastric morphology and histopathology following sleeve gastrectomy in diet-induced obese rats.

BACKGROUND: Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of morbid obesity. The aim of the study was to analyze gastric morphology and histology at two different time points after SG in rats. METHODS: Thirty-five male Wistar rats were fed ad libitum during 3 months on a high-fat diet to induce obesity. Subsequently, 25 diet-induced obese rats underwent either SG (n = 12) or a sham operation (n = 13). The remaining ten obese animals encompassed the nonoperated control group (Co). Four weeks postoperatively, 15 rats (n = 5 rats/experimental group) were sacrificed, while the remaining 20 rats were sacrificed after 16 weeks (animals/group; Co = 5, sham = 8, SG = 7) to compare the gastric morphological and histopathological changes over time. Body weight and food intake were regularly recorded. RESULTS: For both time periods, the Co groups exhibited the highest body weight, while the rats undergoing the SG showed the lowest weight gain (P < 0.05). Initially, significant differences (P < 0.005) in food intake relative to body weight were observed between the Co rats and animals undergoing surgery, which disappeared thereafter. The actual total stomach size after both experimental periods in the SG group was similar to that of non- and sham-operated rats mainly due to a forestomach enlargement, which was more pronounced after 16 weeks. Traits of gastritis cystica profunda characterized by gastric foveolae elongation with hyperplasia and cystic dilatation of the glands were observed in the residual stomachs of the sleeve-gastrectomized rats. These findings were mostly observed after 16 weeks of performing the SG, although they were also detected occasionally following 4 weeks postoperatively. No intestinal metaplasia was observed. CONCLUSION: After SG gastric macro- and microscopic changes with functional implications in both the short and long term take place.