Atypical umbilical endometriosis: Microscopic and immunohistochemical characterization / Endometriosis atípica umbilical. Caracterización microscópica e inmunohistoquímica

Introduction: Atypical endometriosis is considered a precursor lesion to cancer associated with endometriosis. Two types of atypical endometriosis have been proposed: an architectural type with a higher risk of malignancy and a cytological type with a lower potential for malignancy. Main symptoms and/or clinical findings: A 37-year-old Caucasian woman presented with umbilical bleeding coinciding with menstruation. On physical examination, two small, bluish lesions were observed in the umbilical scar. Primary diagnosis: This clinical case is of interest because it describes a lesion of atypical architectural endometriosis located in the navel. Therapeutic interventions and results: The microscopic and immunohistochemical characteristics of the lesion were examined. The presence of nuclear stratification, hyperchromatism, and pleomorphism were observed as microscopic qualities. In terms of the immunohistochemical panel, the degree of cell proliferation was analyzed using Ki 67, BAF250a was used as the surrogate marker of ARID 1A, inflammation was assessed through COX, and estrogen and progesterone receptors were examined. The results showed increased cellular activity, the presence of inflammation, and no mutation of the ARID1a gene, with moderate cell proliferation. Conclusion: Umbilical endometriosis is rare, and while malignancy is infrequent, it is possible. For this reason, a complete anatomopathological study including an immunohistochemical panel should be performed to diagnose atypical endometriosis.(AU)

Introducción: La endometriosis atípica está considerada como una lesión precursora de cáncer asociado a endometriosis. Se han propuesto 2 tipos de endometriosis atípica, una arquitectural con mayor riesgo de malignización y otra citológica cuyo potencial de malignización es menor. Principales síntomas y/o hallazgos clínicos: Una mujer de 37 años caucásica consulta por sangrado catamenial umbilical. A la exploración física se observan 2 pequeñas lesiones umbilicales azuladas. Diagnóstico principal: Este caso clínico es interesante porque se describe una lesión de endometriosis atípica arquitectural localizada en el ombligo. Intervenciones terapéuticas y resultados: Se ha descrito sus características microscópicas e inmunohistoquímicas para caracterizarla. La presencia de estratificación nuclear, hipercromatismo y pleomorfismo como cualidades microscópicas y en cuanto al panel inmunohistoquímico se ha analizado el grado de proliferación celular mediante el Ki-67, BAF250a como el marcador subrogado del ARID1A, el grado de inflamación mediante COX y los receptores estrogénicos y gestagénicos. Los resultados demuestran que tiene una actividad celular aumentada, presencia de inflamación y no mutación del gen ARID1A con moderación proliferación celular. Conclusión: La endometriosis umbilical es poco frecuente y su malignización, aunque rara es posible. Por esta razón, se debería realizar un estudio anatomopatológico completo que incluya un panel inmunohistoquímico en aras de diagnosticar endometriosis atípica.(AU)

Solar photo-Fenton with simultaneous addition of ozone for the treatment of real industrial wastewaters.

Simultaneous application of solar photo-Fenton and ozonation (SPFO) for the efficient treatment of real wastewaters was studied. Four different industrial effluents were selected for the study: landfill leachate, pharmaceutical effluent and two textile wastewaters, in order to demonstrate the effectiveness and versatility of the proposed technology. SPFO performance was compared with individual processes (either solar photo-Fenton or ozonation), as well as the hybrid Fenton and ozonation treatment. In highly polluted wastewaters, combined strategies led to higher organic matter removal than O3 and photo-Fenton processes applied individually. Solar light favoured catalyst regeneration, allowing removal efficiencies up to 67% of chemical oxygen demand (COD) and 62% of total organic carbon (TOC) (in the case of textile wastewaters) using an initial concentration of only 10 mg Fe2+ L-1. The reduction of catalyst consumption, along with the absence of sludge production (since Fe2+ removal from the effluent is not required), led to a significant decrease in operational costs (up to 1.22 € kg-1 COD removed) when combined Fenton and ozonation was applied under solar light. SPFO results in a versatile, effective and economically efficient technology, thus postulating as a promising alternative for reducing the organic load of highly polluted industrial effluents prior to biological treatment.

A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time.

This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 mm, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (<0.2 s).

Patient-specific simulation of the intrastromal ring segment implantation in corneas with keratoconus.

PURPOSE: The purpose of this study was the simulation of the implantation of intrastromal corneal-ring segments for patients with keratoconus. The aim of the study was the prediction of the corneal curvature recovery after this intervention. METHODS: Seven patients with keratoconus diagnosed and treated by implantation of intrastromal corneal-ring segments were enrolled in the study. The 3D geometry of the cornea of each patient was obtained from its specific topography and a hyperelastic model was assumed to characterize its mechanical behavior. To simulate the intervention, the intrastromal corneal-ring segments were modeled and placed at the same location at which they were placed in the surgery. The finite element method was then used to obtain a simulation of the deformation of the cornea after the ring segment insertion. Finally, the predicted curvature was compared with the real curvature after the intervention. RESULTS: The simulation of the ring segment insertion was validated comparing the curvature change with the data after the surgery. Results showed a flattening of the cornea which was in consonance with the real improvement of the corneal curvature. The mean difference obtained was of 0.74 mm using properties of healthy corneas. CONCLUSIONS: For the first time, a patient-specific model of the cornea has been used to predict the outcomes of the surgery after the intrastromal corneal-ring segments implantation in real patients.

Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues.

This paper presents a novel methodology to in-vivo estimate the elastic constants of a constitutive model proposed to characterize the mechanical behavior of the breast tissues. An iterative search algorithm based on genetic heuristics was constructed to in-vivo estimate these parameters using only medical images, thus avoiding invasive measurements of the mechanical response of the breast tissues. For the first time, a combination of overlap and distance coefficients were used for the evaluation of the similarity between a deformed MRI of the breast and a simulation of that deformation. The methodology was validated using breast software phantoms for virtual clinical trials, compressed to mimic MRI-guided biopsies. The biomechanical model chosen to characterize the breast tissues was an anisotropic neo-Hookean hyperelastic model. Results from this analysis showed that the algorithm is able to find the elastic constants of the constitutive equations of the proposed model with a mean relative error of about 10%. Furthermore, the overlap between the reference deformation and the simulated deformation was of around 95% showing the good performance of the proposed methodology. This methodology can be easily extended to characterize the real biomechanical behavior of the breast tissues, which means a great novelty in the field of the simulation of the breast behavior for applications such as surgical planing, surgical guidance or cancer diagnosis. This reveals the impact and relevance of the presented work.

Substitution of insulin by exenatide in bad controlled type 2 diabetic patients: efficacy and predictive factors.

AIM: Exenatide therapy is indicated in type 2 diabetes after failure of oral antidiabetic agents (OAD). The aim of this observational prospective study was to assess efficacy of exenatide, in improving HbA1c of at least of 1% (responders) in type 2 diabetic patients treated previously with insulin. METHODS: Thirty-six patients (HbA1c >7.5%), with chronic bad glycemic control, were hospitalized to improve glycemia using transient continuous insulin infusion followed by administration of exenatide and OAD agents. In these patients, insulin had been introduced previously because of OAD failure without any sign of severe insulin deficiency. RESULTS: On the 27 patients analyzed at 3 months, 19 patients were responders (HbA1c: M0: 9.9±1.7%; M3: 7.6±1.2%). Among the 8 non-responders, only 4 deteriorated their HbA1c. After 9 months, 10 patients remained Responders (HbA1c: 7±0.9%). Predictive factors for an improvement of glycemic control were: diabetes duration shorter than 12 years, ratio fasting glycemia/C-peptide less than 1, fasting C-peptide higher than 2.0 µg/L and mean capillary blood glucose after 3 days of exenatide lower than 200 mg/dL. These criteria remained valid in case of a high HbA1c at baseline. CONCLUSION: In patients with no signs of insulin dependence and in case of insulin failure, exenatide associated to OAD may be tried in order to improve glycemic control, this objective was reached by 70% of our patients. Predictive factors for good response, easily available in clinical practice, may help therapeutic choices.

Strategies to evaluate biodegradability: application to chlorinated herbicides.

The biodegradability of nitrochlorinated (diuron and atrazine) and chlorophenoxy herbicides (2,4-D and MCPA) has been studied through several bioassays using different testing times and biomass/substrate ratios. A fast biodegradability test using unacclimated activated sludge yielded no biodegradation of the herbicides in 24 h. The inherent biodegradability test gave degradation percentages of around 20-30% for the nitrochlorinated herbicides and almost complete removal of the chlorophenoxy compounds. Long-term biodegradability assays were performed using sequencing batch reactor (SBR) and sequencing batch membrane bioreactor (SB-MBR). Fixed concentrations of each herbicide below the corresponding EC50 value for activated sludge were used (30 mg L(-1) for diuron and atrazine and 50 mg L(-1) for 2,4-D and MCPA). No signs of herbicide degradation appeared before 35 days in the case of diuron and atrazine and 21 days for 2,4-D, whereas MCPA was partially degraded since the early stages. Around 25-36% degradation of the nitrochlorinated herbicides and 53-77% of the chlorophenoxy ones was achieved after 180 and 135 days, respectively, in SBR, whereas complete disappearance of 2,4-D was reached after 80 days in SB-MBR.

Coupling Fenton and biological oxidation for the removal of nitrochlorinated herbicides from water.

The combination of Fenton and biological oxidation for the removal of the nitrochlorinated herbicides alachlor, atrazine and diuron in aqueous solution has been studied. The H2O2 dose was varied from 20 to 100% of the stoichiometric amount related to the initial chemical oxygen demand (COD). The effluents from Fenton oxidation were analyzed for ecotoxicity, biodegradability, total organic carbon (TOC), COD and intermediate byproducts. The chemical step resulted in a significant improvement of the biodegradability in spite of its negligible or even slightly negative effect on the ecotoxicity. Working at 60% of the stoichiometric H2O2 dose allowed obtaining highly biodegradable effluents in the cases of alachlor and atrazine. That dose was even lower (40% of the stoichiometric) for diuron. The subsequent biological treatment was carried out in a sequencing batch reactor (SBR) and the combined Fenton-biological treatment allowed up to around 80% of COD reduction.

Comparison of experimental methods for determination of toxicity and biodegradability of xenobiotic compounds.

Different methods for determining the toxicity and biodegradability of hazardous compounds evaluating their susceptibility to biological treatment were studied. Several compounds including chlorophenols and herbicides have been evaluated. Toxicity was analyzed in terms of EC50 and by a simple respirometric procedure based on the OECD Method 209 and by the Microtox® bioassay. The values of EC50 obtained from respirometry were in all the cases higher than those from the Microtox® test. The respirometric inhibition values of chlorophenols were related well with the number of chlorine atoms and their position in the aromatic ring. In general, herbicides showed lower inhibition, being alachlor the less toxic from this criterion. For determination of biodegradability an easier and faster alternative to the OECD Method 301, with a higher biomass to substrate ratio is proposed. When this test was negative, the Zahn-Wellens one was performed in order to evaluate the inherent biodegradability. In the fast test of biodegradability, 4-chlorocatechol and 4-chlorophenol showed a complete biodegradation by an unacclimated sludge upon 48 h. These results together with their low respirometric inhibition, allow concluding that these compounds could be conveniently removed in a WWTP. Alachlor, 2,4-dichlorophenol, 2,4,6-trichlorophenol and MCPA showed a partial biodegradation upon 28 days by the Zahn-Wellens inherent biodegradability test.

Colgajo en hélice de perforante interósea posterior. Un nuevo procedimiento reconstructivo / Propeller interoseous posterior perforator flap. A new reconstructive procedure

El colgajo interóseo posterior de pedículo distal se basa en el arco anastomótico dorsal formado por las arterias interóseas anterior y posterior. Cuando dicha arcada está interrumpida, no es posible elevar un colgajo interóseo posterior de pedículo distal. Presentamos un colgajo de perforante interósea posterior diseñado en hélice, disponible en ausencia de la arcada vascular dorsal y útil en la cobertura de tercio distal del antebrazo, carpo y mano. Detallamos la técnica quirúrgica, sus aplicaciones, ventajas e inconvenientes y analizamos el empleo de este tipo de colgajo en diferentes casos. Presentamos el caso de un paciente con exposición de material de osteosíntesis en tercio distal de radio y trombosis de las anastomosis de revascularización tras sufrir aplastamiento severo de su miembro superior izquierdo; el examen con Doppler reveló ausencia de flujo reverso en la arteria interósea posterior. Se practicó un colgajo en hélice de perforanteinterósea posterior para cubrir el nuevo by-pass y la osteosíntesis. También otro paciente que tras un accidente de automóvil sufrió fracturas cerradas de cúbito y radio en su miembro superior izquierdo. La columna radial del carpo presentaba una severa lesión por aplastamiento. Tras las osteosíntesis, se practicó un colgajo en hélice de perforanteinterósea posterior para cobertura de la cara dorso-radial del carpo. En los casos clínicos presentados el colgajo en hélice de perforanteinterósea posterior proporcionó excelente cobertura del carpo y de la mano con escasa morbilidad de la zona donante. El colgajo en hélice de perforante interósea posterior se presenta como una opción versátil y segura para la cobertura del tercio distal de miembro superior, pudiendo ser elevado en ausencia de flujo reverso y sin sacrificio de la arteria interósea posterior (AU)

The distally-based posterior interosseous flap is a versatile and useful technique in upper limb reconstruction. This flap is based on the integrity of the dorsal carpal anastomosis between the anterior interosseous artery and the posterior interosseous artery. Hence, when the dorsal carpal anastomosisis not available, it is not possible to perform a distally-based posteriorinterosseous flap. We report a propeller perforator flap proximally based, available without the dorsal carpal supply, and useful for the coverage of the distal third of the forearm, wrist and hand. We report the surgical technique, its applications, advantages and disadvantages and review the use o this flap in different clinical cases. A patient suffered a severe crush injury of their left upper limb. He presented osteosynthesis plate exposure in the radius and thrombosis of there vascularization anastomosis. The absence of reverse flow in the posteriorinterosseous artery was proven with Doppler Ultrasounds. A propellerinterosseous posterior perforator flap was performed to cover a new by-pass and the osteosynthesis plate. Another patient suffered an automobile accident. He presented closed fractures of radius and ulna of their left upper limb. The radial column of carpus suffered a severe crush injury. After the osteosynthesis, a propellerinterosseous posterior perforator flap was performed. The flap provided appropriate coverage of the dorso-radial aspect of the wrist andhand. In our clinical cases the propeller interosseous posterior perforator flap provided excellent coverage of the carpus and hand with low donorsite morbidity. Propeller interosseous posterior perforator flap provide a versatile and reliable coverage option in upper limb reconstruction, available in absence of the dorsal carpal anastomosis and without sacrifice of the interosseous posterior artery (AU)

Association of malignant insulinoma and type 2 diabetes mellitus: a case report.

We report a case of recurrent hypoglycemia due to malignant insulinoma in a type 2 diabetic patient correctly controlled for years with the same doses of oral antidiabetic agents. A 79-year-old woman was admitted for recurrent severe hypoglycemia. She had a history of type 2 diabetes since 2000. HbA1c was 7.8% when she reported mild hypoglycemia and 5.8% when recurrent hypoglycemia appeared despite progressive diminution of glicazide. Severe hypoglycemia continued despite interrupting diabetes medications. At admission, results showed inappropriately elevated insulin, C-peptide and proinsulin levels despite significant hypoglycemia. CT scan showed "cystic" nodes in the pancreas and in the liver. Liver biopsy found a well-differentiated neuroendocrine carcinoma with positive staining for chromogranin A and negative staining for insulin. Hypoglycemia improved with diazoxide, lanreotide and dextrose infusion. Liver chemoembolization was planned. Severe edema, dyspnea, hyponatremia, and hypo-osmolarity occurred. The patient's clinical status deteriorated rapidly with severe cardiac, renal and hepatic failure. She died in a few days. Association of diabetes mellitus and insulinoma is extremely rare. Malignant insulinoma survival is less than two years, shorter when hepatic localizations are present at diagnosis. Association of diabetes with insulinoma delays the diagnosis, but does not alter prognosis or favor carcinoma frequency. Lanreotide was inefficient in our patient despite good responses described in the literature. Heart, respiratory and renal failures have been described with diazoxide independently of the doses; this may in part explain the rapid death. Insulinoma should be considered as a cause of unusual and recurrent hypoglycemia in a diabetic patient especially if it persists after interrupting antidiabetic agents.

Efficacy of pioglitazone in familial partial lipodystrophy of the Dunnigan type: a case report.

A 25 year old woman consulted for a severe acanthosis nigricans and central distribution of fat. Her masculine type morphology was associated with muscular appearance of the limbs and excess fat deposits in the face and neck. Biological testing confirmed glucose intolerance associated with a severe insulin resistance, hypertriglyceridemia and polycystic ovary syndrome. The detection of a heterozygous missense mutation in LAMIN A/C gene at position 482 confirmed the diagnosis of Familial Partial Lipodystrophy (FPLD2). Due to a deterioration of clinical and metabolic status, 15 and then 30 mg per day of pioglitazone were added to her previous treatment with metformin, bezafibrate and omega-3 fatty acids. Metabolic status improved rapidly after 3 months and continued thereafter. Weight remained stable, body mass composition and waist circumference improved. After 18 months of treatment, glycaemia and triglycerides levels normalized, hepatic enzymes and liver echographic features improved. Insulin sensitivity improved dramatically with a HOMA % S value of 73% with metformin and of 98.2% when pioglitazone was added. Leptin levels increased from 6.6 to 10.2 microg/ml. We report a very rapid and good efficacy of pioglitazone added to metformin without side effects in FPLD2. If confirmed on more patients, early use of pioglitazone in association with metformin could be proposed in FPLD2.

Efficacy of short term continuous subcutaneous insulin lispro versus continuous intravenous regular insulin in poorly controlled, hospitalized, type 2 diabetic patients.

UNLABELLED: Intravenous insulin infusion (IVII) is rapidly effective in improving glycaemia in uncontrolled hospitalized diabetic patients. This significantly improves their morbidity and mortality. Intravenous insulin infusion may lead to IV infusion complications and is a heavy burden for caregivers. AIM: The aim of our work was to compare the efficacy of IV regular insulin versus lispro Continuous Subcutaneous Insulin Infusion (CSII), in improving glycaemia in patients hospitalized for uncontrolled type 2 diabetes, the efficacy being assessed on the average blood glucose level observed. METHODS: The study was designed as a prospective randomized study. Thirty-three type 2 diabetic patients, hospitalized for uncontrolled diabetes by their usual practitioner were included. After acceptation, patients were randomly assigned to lispro CSII (group 1, n=20) or IVII regular insulin (group 2, n=13) for 5 days. Ten capillary blood glucose/day were performed. Pre-meal blood glucose targets were 4.4-6.6 mmol/l. Mann Whitney, Wilcoxon and Fischer exact tests were used. RESULTS: BG levels decreased significantly (-3.4+/-0.55 mmol/l in group 1 and -3.60+/-0.55 mmol/l in group 2, P<0.01) during the first 12 hours. Mean daily blood glucose at day 5 was statistically improved in both groups compared to day 1 (P<0.05 Wilcoxon) and comparable between the 2 groups. No severe hypoglycaemia was reported. No catheter complications occurred in group 1, 7 occurred in group 2. CONCLUSION: CSII and IVII infusion were comparable in rapidly improving hyperglycaemia in uncontrolled type 2 diabetic patients. CSII, being more convenient, could be preferred in medical and surgical settings.

[Hyperglycemia and acute illness]. / Hyperglycémie et pathologies aiguës.

Hyperglycemia due to acute illness is frequently observed in non-diabetic patients. Considered as a physiological response to inflammation, it has now been shown to be an independent factor of morbid-mortality in critically ill patients. Hyperglycemia reduces the immune system response to aggression by decreasing the efficacy of some complement factors and polynuclear cells chemotactism and phagocytosis and by increasing the inflammatory response (cytokines, NF-kB and CRP). Glycemia near normalization using intensive insulin therapy significantly improves mortality and morbidity in several critical illnesses such as cardiac or infectious diseases. This improvement is probably due to the neutralization of deleterious effects caused by hyperglycemia and to the specific actions of insulin on the inflammatory response. Except for ICU patients, precise management protocols of hyperglycemia due to acute illness remain to be proposed and evaluated in clinical practice.

Cocaine-induced locomotor activity is enhanced by exogenous testosterone.

Anabolic-androgenic steroids are synthetic derivatives of testosterone, which are increasingly abused by adolescent populations who also abuse psychoactive substances. All these compounds lead to complex behavioral syndromes and the effects of their interactions remain unclear. The main aim of the present study was to determine the influence of testosterone on the locomotor activity-promoting effect of cocaine on male mice in an open field. In the three experiments, animals received two injections: firstly, testosterone or peanut oil, and secondly, cocaine or saline solution. In Experiments 1 and 2, testosterone (or oil) and cocaine (or saline) were injected 45 and 10 min, respectively, prior to activity recording. In the first experiment, we studied the effects of testosterone (2 mg/kg) on locomotor activity induced by different doses of cocaine (2, 4, 8, 10 or 12 mg/kg). In Experiment 2, we explored the effects of supraphysiological doses of testosterone (2, 6, 10 or 14 mg/kg) on animals treated with 10 mg/kg cocaine. Finally, in the third experiment, 14 mg/kg testosterone or vehicle was administered 15, 30, 45 or 75 min before activity data collection to animals that received 10 mg/kg cocaine or saline. Testosterone itself had no effects on spontaneous locomotor activity and, as was expected, cocaine increased locomotor activity dose-dependently. Given together, testosterone enhanced the cocaine-induced hyperactivity although not dose-dependently, the highest effects being found 45 min after testosterone injection. The present study confirmed the existence of an interaction between testosterone and cocaine at the central nervous system.

[Physiological basis of insulin secretion abnormalities]. / Les bases physiologiques des troubles de l'insulinosécrétion.

The pathogenesis of type 2 diabetes is complex, with two distinct mechanisms: insulin resistance (decrease of insulin action on peripheral tissues) and insulin deficiency (impaired insulin secretion by pancreatic beta-cells). These abnormalities are due to genetic and environmental factors. Type 2 diabetes is a heterogeneous disease: besides the common form with obesity, monogenic forms (such as MODY) exist. Knowledge of these forms has permit a better understanding of the genetic factors involved in diabetes, and of their relationship with insulin resistance. In this review, we discuss the main data available on genetics of type 2 diabetes, as well as the various research approaches. Today, the genetic determinism of functional abnormalities of pancreatic beta-cell is no longer discussed. However, it is also clearly established that acquired metabolic factors may contribute to pancreatic beta-cell failure. Hyperglycaemia, even moderate, induces a reduced insulin biosynthesis potential (glucotoxicity), and the increased free fatty acid flux accelerates pancreatic beta-cell apoptosis (lipotoxicity). The role of these metabolic abnormalities in the development of type 2 diabetes is briefly described.

Ética del tratamiento hormonal sustitutivo de la menopausia con estrógenos y gestágenos / Ethics of hormone replacement therapy with estrogens and gestagens in menopause

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