Breast Vascularization and Its Implication in Breast Reduction and Mastopexy Surgery: Anatomical Study.

(1) Background: Breast reduction is one of the most frequently performed plastic surgeries in women worldwide. The Wise pattern breast reduction is one of the most frequent skin designs for this surgery. One key point of the surgery is to preserve a well-vascularized NAC by using different surgical pedicles. This study aims to test and update the anatomical knowledge of breast vascularization, the topographic and anatomical basis of the different surgical vascular pedicles, and the differences between the right and left sides. (2) Methods: A descriptive observational anatomical study was carried out on 15 breasts from 10 cryopreserved body donors. A dissection was performed by quadrants to know the affected arteries' origin in the different patterns. (3) Results: The largest and most frequently dissected internal mammary perforator artery was in the second intercostal space. A total of 44.9% of the dissected perforators are located in the upper inner quadrant, compared to 53.5% in the lower quadrants. (4) Conclusions: The upper inner quadrant alone has the most arterial perforators. In contrast, the sum of the two lower quadrants represents the greatest vascularization of the breast, with a small difference between both.

Evaluating restriction enzyme selection for reduced representation sequencing in conservation genomics.

Conservation genomic studies in non-model organisms generally rely on reduced representation sequencing techniques based on restriction enzymes to identify population structure as well as candidate loci for local adaptation. While the expectation is that the reduced representation of the genome is randomly distributed, the proportion of the genome sampled might depend on the GC content of the recognition site of the restriction enzyme used. Here, we evaluated the distribution and functional composition of loci obtained after a reduced representation approach using Genotyping-by-Sequencing (GBS). To do so, we compared experimental data from two endemic fish species (Symphodus ocellatus and Symphodus tinca, EcoT22I enzyme) and two ecosystem engineer sea urchins (Paracentrotus lividus and Arbacia lixula, ApeKI enzyme). In brief, we mapped the sequenced loci to the phylogenetically closest reference genome available (Labrus bergylta in the fish and Strongylocentrotus purpuratus in the sea urchin datasets), classified them as exonic, intronic and intergenic, and studied their function by using Gene Ontology (GO) terms. We also simulated the effect of using both enzymes in the two reference genomes. In both simulated and experimental data, we detected an enrichment towards exonic or intergenic regions depending on the restriction enzyme used and failed to detect differences between total loci and candidate loci for adaptation in the empirical dataset. Most of the functions assigned to the mapped loci were shared between the four species and involved a myriad of general functions. Our results highlight the importance of restriction enzyme selection and the need for high-quality annotated genomes in conservation genomic studies.

Possible EU futures for CRISPR-edited plants: Little margin for optimism?

This article addresses the scenarios that may be encountered by the first application for pre-market approval of a CRISPR-edited plant in the EU. Two alternative scenarios are considered in the short and medium term. One of these possible EU futures depends on the final drafting and approval of EU legislation on certain New Genomic Techniques, which was started in 2021 and is due to be quite advanced before the next European Parliament elections in 2024. Since the proposed legislation excludes plants with foreign DNA, two different approval processes for CRISPR-edited plants will coexist if the legislation enters into force: one for plants whose genome has been altered, resulting in mutagenesis, cisgenesis and intragenesis; and the second for plants whose alterations result in transgenesis in general. In the event that this legislative process does not succeed, CRISPR-edited plants in the EU could face a regulatory scenario whose foundations were laid in the 1990s: the regulatory framework that applies to GM crops, food and feed. In this review, an ad hoc analytical framework has been built that considers in depth the two possible futures for CRISPR-edited plants in the EU. This framework emphasises the way in which the European Union and the Member States (MS), with their respective national interests, have historically shaped the regulatory framework for plant breeding in the EU. On the basis of the analyses carried out on the two possible futures for CRISPR-edited plants and of their potential with respect to plant breeding, the main conclusions are the following. Firstly, that the regulatory review that started in 2021 is not in itself "good enough" for plant breeding and CRISPR-edited plants. Secondly, that compared to its alternative, the regulatory review currently underway contains at least some promising improvements in the short term. Hence, thirdly, in addition to adopting the current regulation, the MS need to continue to work towards a substantial improvement in the legal status of plant breeding in the EU in the medium term.

Abacavir causes leukocyte/platelet crosstalk by activating neutrophil P2X7 receptors thus releasing soluble lectin-like oxidized low-density lipoprotein receptor-1.

BACKGROUND AND PURPOSE: Abacavir, an antiretroviral drug used in HIV therapy associated with myocardial infarction, promotes thrombosis through P2X7 receptors. The role of platelets as pro-thrombotic cells is acknowledged whereas that of neutrophils-due to their secretory capacity-is gaining recognition. This study analyses the role of neutrophils-specifically the secretome of abacavir-treated neutrophils (SNABC )-in platelet activation that precedes thrombosis. EXPERIMENTAL APPROACH: Effects of abacavir or SNABC on platelet activation and platelet-leukocyte interactions and expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were analysed by flow cytometry. The secretome was analysed by proteomics. The role of leukocytes in the actions of abacavir was evaluated in a mouse model of thrombosis. KEY RESULTS: Abacavir induced platelet-leukocyte interactions, not directly via effects of abacavir on platelets, but via activation of neutrophils, which triggered interactions between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1 (PSGL-1). SNABC stimulated platelet activation and platelet-leukocyte interactions through a process that was dependent on LOX-1, neutrophil P2X7 and platelet P2Y1, P2Y12 and P2X1 receptors. Abacavir induced the expression of LOX-1 on neutrophils and of the soluble form of LOX-1 (sLOX-1) in SNABC . Neutrophils, LOX-1, P2X7, P2Y1, P2Y12 and P2X1 receptors were required for the pro-thrombotic actions of abacavir in vivo. CONCLUSION AND IMPLICATIONS: Neutrophils are target cells in abacavir-induced thrombosis. Abacavir released sLOX-1 from neutrophils via activation of their P2X7 receptors, which in turn activated platelets. Hence, sLOX-1 could be the missing link in the cardiovascular risk associated with abacavir.

The Chemistry of Zirconium/Carboxylate Clustering Process: Acidic Conditions to Promote Carboxylate-Unsaturated Octahedral Hexamers and Pentanuclear Species.

Clustering chemistry is a key point in the design and synthesis of the secondary building units that comprise metal-organic frameworks (MOFs) based on group IV metals. In this work, the first stages of the zirconium-carboxylate clustering process in alcohol/water mixtures are studied in detail using the monocarboxylic benzoic and hydroxybenzoic acids to avoid the polymerization. Mass spectroscopy measurements performed on the reactions revealed the presence of hexa- and pentanuclear species even at low pH values and also evidenced the acid-base nature and pH dependence of the transformation between both species. The control on the chemistry governing the equilibria between these species has allowed us to isolate six new compounds in the solid state. The single-crystal X-ray diffraction analysis revealed that they are closely related to the well-known [Zr6(O)4(OH)4(OOC)12] secondary building unit found in many MOFs by removing carboxylic ligands in the case of the hexameric species ([Zr6(O)4(OH)4(OOC)8(H2O)8]4+) or by additionally removing one of the metal centers in the case of the pentameric entities ([Zr5(O)2(OH)6(OOC)4(H2O)11(alcohol)]6+). Going in detail, the unsaturated hexameric clusters exhibit different dispositions of their eight carboxylate ligands in such a way that the remaining four carboxylate-free positions are arranged according to a square planar or tetrahedral symmetry. It should be highlighted that the pentameric complexes imply an unprecedented core nuclearity in zirconium clusters and thus their isolation provides a novel building block for the design of metal-organic materials.

Abacavir Increases Purinergic P2X7 Receptor Activation by ATP: Does a Pro-inflammatory Synergism Underlie Its Cardiovascular Toxicity?

The cardiovascular toxicity of Abacavir is related to its purinergic structure. Purinergic P2X7-receptors (P2X7R), characterized by activation by high concentrations of ATP and with high plasticity, seem implicated. We appraise the nature of the interplay between Abacavir and P2X7R in generating vascular inflammation. The effects of Abacavir on leukocyte-endothelium interactions were compared with those of its metabolite carbovir triphosphate (CBV-TP) or ATP in the presence of apyrase (ATP-ase) or A804598 (P2X7R-antagonist). CBV-TP and ATP levels were evaluated by HPLC, while binding of Abacavir, CBV-TP and ATP to P2X7R was assessed by radioligand and docking studies. Hypersensitivity studies explored a potential allosteric action of Abacavir. Clinical concentrations of Abacavir (20 µmol/L) induced leukocyte-endothelial cell interactions by specifically activating P2X7R, but the drug did not show affinity for the P2X7R ATP-binding site (site 1). CBV-TP levels were undetectable in Abacavir-treated cells, while those of ATP were unaltered. The effects of Abacavir were Apyrase-dependent, implying dependence on endogenous ATP. Exogenous ATP induced a profile of proinflammatory actions similar to Abacavir, but was not entirely P2X7R-dependent. Docking calculations suggested ATP-binding to sites 1 and 2, and Abacavir-binding only to allosteric site 2. A combination of concentrations of Abacavir (1 µmol/L) and ATP (0.1 µmol/L) that had no effect when administered separately induced leukocyte-endothelium interactions mediated by P2X7R and involving Connexin43 channels. Therefore, Abacavir acts as a positive allosteric modulator of P2X7R, turning low concentrations of endogenous ATP themselves incapable of stimulating P2X7R into a functional proinflammatory agonist of the receptor.

Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor.

The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels-inexistent in physiological conditions-are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-gated P2X7R is a homo-trimeric receptor channel that is occasionally hetero-trimeric and highly polymorphic, with at least nine human splice variants. It is localized predominantly in the cellular membrane and has a characteristic plasticity due to an extended C-termini, which confers it the capacity of interacting with membrane structural compounds and/or intracellular signaling messengers to mediate flexible transduction pathways. Diverse drugs and a few endogenous molecules have been highlighted as extracellular allosteric modulators of P2X7R. Therefore, studies in human cells that constitutively express P2X7R need to investigate the precise endogenous mediator located nearby the activation/modulation domains of the receptor. Such research could help us understand the possible physiological ATP-mediated P2X7R homeostasis signaling.

Environmental factors are associated with hospital admissions for sepsis-related pneumonia: A bidirectional case-crossover design.

OBJECTIVE: Pneumonia is a common cause of morbidity and sepsis worldwide, mainly in the elderly. We evaluated the impact of short-term exposure to environmental factors on hospital admissions for sepsis-related pneumonia in a nationwide study in Spain. METHODS: We conducted a bidirectional case-crossover study in patients who had sepsis-related pneumonia in 2013. Data were obtained from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. Conditional logistic regressions were used to evaluate the association between environmental factors (temperature, relative humidity, NO2, SO2, O3, PM10, and CO) and hospital admissions with sepsis-related pneumonia. RESULTS: A total of 3,262,758 hospital admissions were recorded in the MBDS, of which, 253,467 were patients with sepsis. Among those, 67,443 had sepsis-related pneumonia and zip code information. We found inverse associations [adjusted odds ratio (aOR) values < 1] between short-term exposure to temperature and hospital admissions for sepsis-related pneumonia. Moreover, short-term exposure to higher levels of relative humidity, NO2, SO2, O3, PM10, and CO were directly associated (aOR values > 1) with a higher risk of hospital admissions for sepsis-related pneumonia. Overall, the impact of environmental factors was more prominent with increasing age, mainly among the elderly aged 65 or over. CONCLUSION: Short-term exposure to environmental factors (temperature, relative humidity, NO2, SO2, O3, CO, and PM10) was associated with a higher risk of hospital admissions for sepsis-related pneumonia. Our findings support the role of environmental factors in monitoring the risk of hospital admissions for sepsis-related pneumonia and can help plan and prepare public health resources.

Phenotype and resistance patterns of 10 resistant prolactinomas / Fenotipo y patrones de resistencia de 10 prolactinomas resistentes

Background: Dopamine agonists (DA) are the first-line therapy in prolactinomas, but they fail to decrease prolactin (PRL) levels and/or tumor size in some of these tumors, which are labeled as resistant prolactinomas (RP). To date, risk factors for DA resistance are not fully understood and management of DA-RP is not well established. Methods: We retrospectively recorded clinical, biochemical and radiological features, as well as management and outcome, of all cabergoline (CAB)-RP attended at the Endocrinology department of a tertiary hospital between 1995 and 2016. CAB resistance was defined as the failure to normalize PRL (biochemical resistance, BR) or reduce tumor size by at least 50% (morphological resistance, MR) with a CAB dose up to 2 mg/week (or 3 mg/week in cases where lower doses were not tested) for at least 3 months. Results: Ten CAB-RP were found. The mean age of the cohort was 30.6 years and 50% of subjects were male. The average tumor size was 1.78 cm (80% macroadenomas). The mean maximal dose of CAB was 3.8 mg/week. Five patients showed isolated MR, four combined MR + BR and only one isolated BR. MR patients were more often males and older than MR + BR patients. Transsphenoidal surgery achieved normalization of PRL and/or disappearance of tumor in three of seven patients. At the end of follow up all patients had controlled PRL levels (with or without CAB) and most of them bore a visible although stable tumor. Conclusions: Isolated MR and combined MR + BR are the most frequent patterns of DA resistance whereas isolated BR seems to be uncommon. Our data support a high tumor size but not male gender as a risk factor for DA resistance

Contexto: Los agonistas dopaminérgicos (AD) son el tratamiento de elección de los prolactinomas, pero en algunos casos no logran normalizar los niveles de prolactina (PRL) o disminuir el tamaño del tumor, y estos casos se etiquetan como prolactinomas resistentes (PR). Los factores de riesgo de resistencia a los AD y el manejo de los PR no están bien establecidos. Métodos: Analizamos retrospectivamente las características clínicas, bioquímicas y radiológicas, así como el manejo y evolución de los PR a cabergolina (CAB) atendidos en el departamento de Endocrinología de un hospital terciario entre 1995 y 2016. La resistencia a CAB se definió como persistencia de PRL elevada (resistencia bioquímica, RB) o reducción tumoral inferior al 50% (resistencia morfológica, RM) tras al menos 3 meses de tratamiento con una dosis de CAB de hasta 2 mg/semana (o 3 mg/semana en los casos que no recibieron dosis inferiores) Resultados: Se incluyeron 10 pacientes, edad media 30.6 años, 50% varones. El tamaño medio del tumor fue 1.78 cm (80% macroadenomas) y la dosis máxima media de CAB 3.8 mg/semana. Cinco pacientes presentaron RM aislada, cuatro RM + RB y uno RB aislada. La prevalencia de sexo masculino y la edad fueron superiores en el grupo RM comparado con el grupo RM + RB. La cirugía transesfenoidal logró normalización de PRL y/o desaparición del tumor en tres de siete pacientes. Al final del seguimiento la PRL era normal (con o sin CAB) en todos los casos y la mayoría presentaba un tumor visible de tamaño estable. Conclusiones: la RM aislada y la RM+RB combinadas son los patrones más frecuentes de resistencia a los AD. Nuestros datos apoyan la asociación del tamaño tumoral pero no del sexo masculino con la resistencia a los AD

Phenotype and resistance patterns of 10 resistant prolactinomas.

BACKGROUND: Dopamine agonists (DA) are the first-line therapy in prolactinomas, but they fail to decrease prolactin (PRL) levels and/or tumor size in some of these tumors, which are labeled as resistant prolactinomas (RP). To date, risk factors for DA resistance are not fully understood and management of DA-RP is not well established. METHODS: We retrospectively recorded clinical, biochemical and radiological features, as well as management and outcome, of all cabergoline (CAB)-RP attended at the Endocrinology department of a tertiary hospital between 1995 and 2016. CAB resistance was defined as the failure to normalize PRL (biochemical resistance, BR) or reduce tumor size by at least 50% (morphological resistance, MR) with a CAB dose up to 2mg/week (or 3mg/week in cases where lower doses were not tested) for at least 3 months. RESULTS: Ten CAB-RP were found. The mean age of the cohort was 30.6 years and 50% of subjects were male. The average tumor size was 1.78cm (80% macroadenomas). The mean maximal dose of CAB was 3.8mg/week. Five patients showed isolated MR, four combined MR+BR and only one isolated BR. MR patients were more often males and older than MR+BR patients. Transsphenoidal surgery achieved normalization of PRL and/or disappearance of tumor in three of seven patients. At the end of follow up all patients had controlled PRL levels (with or without CAB) and most of them bore a visible although stable tumor. CONCLUSIONS: Isolated MR and combined MR+BR are the most frequent patterns of DA resistance whereas isolated BR seems to be uncommon. Our data support a high tumor size but not male gender as a risk factor for DA resistance.

Diabetes mellitus tipo 1 y nocturnidad: a propósito de un caso / Type 1 diabetes mellitus and night work: a case report

Se describe el caso de una mujer de 24 años, médico interno residente de un hospital de tercer nivel, diagnosticada de Diabetes Mellitus tipo I en tratamiento con la terapia de infusión subcutánea de insulina, con una hemoglobina glicosilada de 7,5%. Desde el servicio de Prevención de Riesgos Laborales se solicita valoración por el servicio de Endocrinología, que informa que desde el punto de vista médico no existe contraindicación para la realización de nocturnidad (guardias médicas de 24 horas) debido al buen control de la enfermedad, la ausencia de complicaciones y el excelente conocimiento por parte de la paciente de su enfermedad y del autocontrol de la misma. Por tanto, se emite aptitud de la trabajadora con controles periódicas. Revisando la bibliografía, hay que destacar que la diabetes y el trabajo nocturno no son siempre incompatibles y que debe imperar siempre el buen criterio y la individualización de cada caso

We describe the case of a 24-year-old woman, an resident medical intern in an accredited hospital, diagnosed with Type I Diabetes Mellitus under treatment with subcutaneous insulin infusion therapy, with a glycosylated hemoglobin of 7.5%. From the Occupational Health service, a valuation was requested by the Endocrinology service, which informs that from the medical point of view there is no contraindication for the performance of night shifts (24-hour medical guards) due to good control of the disease, absence of complications and the excellent knowledge on the part of the patient of her illness and the self-control of it. Therefore, the worker’s aptitude is issued with periodic checks. Reviewing the bibliography, it should be noted that diabetes and night work are not always incompatible and that good judgment and individualization of each case should always prevail

Dimensional changes of the carpal tunnel and median nerve during manual mobilization of the carpal bones - Anatomical study.

STUDY DESIGN: Cross-sectional study. BACKGROUND: The carpal tunnel is a clinically important fibro-osseous conduit for the median nerve and associated tendons. It is mechanically dynamic and therapeutic manual techniques that appear to move and change tunnel shape is part of clinical practice. OBJECTIVES: To measure changes in dimensions of the carpal tunnel and median nerve with manual mobilization of the carpal bones in cadavers. METHODS: A total of 20 cryopreserved upper extremities from cadaveric specimens were used in the study. The wrist was cut using an anatomical saw at the level of the pisiform. Measurements of the cross-sectional area (CSA), anteroposterior diameter (APD), transverse diameter (TD), perimeter, flattening ratio and circularity of the carpal tunnel and of the median nerve, were taken, both in the anatomical position of the wrist and during the mobilization technique of the carpal bones. RESULTS: During the mobilization technique, the tunnel CSA (p < 0.011), APD (p < 0.001) and circularity (p < 0.001) significantly increased, while TD (p < 0.001), perimeter (p < 0.004) and flattening ratio (p < 0.001), decreased. The median nerve showed similar behavioral tendencies to the tunnel but only the CSA (p < 0.005), APD (p < 0.005) and flattening ratio (p < 0.004) of the nerve showed significant differences. CONCLUSION: Application of external manually applied compressive force across the wrist can increase the CSA of the carpal tunnel and the median nerve in cadavers. These results are consistent with other studies in which similar results were found non-invasively using ultrasound.

Epidemiological trends of sepsis in the twenty-first century (2000-2013): an analysis of incidence, mortality, and associated costs in Spain.

BACKGROUND: Sepsis has represented a substantial health care and economic burden worldwide during the previous several decades. Our aim was to analyze the epidemiological trends of hospital admissions, deaths, hospital resource expenditures, and associated costs related to sepsis during the twenty-first century in Spain. METHODS: We performed a retrospective study of all sepsis-related hospitalizations in Spanish public hospitals from 2000 to 2013. Data were obtained from records in the Minimum Basic Data Set. The outcome variables were sepsis, death, length of hospital stay (LOHS), and sepsis-associated costs. The study period was divided into three calendar periods (2000-2004, 2005-2009, and 2010-2013). RESULTS: Overall, 2,646,445 patients with sepsis were included, 485,685 of whom had died (18.4%). The incidence of sepsis (events per 1000 population) increased from 3.30 (2000-2004) to 4.28 (2005-2009) to 4.45 (2010-2013) (p < 0.001). The mortality rates from sepsis (deaths per 10,000 population) increased from 6.34 (2000-2004) to 7.88 (2005-2009) to 7.89 (2010-2013) (p < 0.001). The case fatality rate (CFR) or proportion of patients with sepsis who died decreased from 19.1% (2000-2004) to 18.4% (2005-2009) to 17.9% (2010-2013) (p < 0.001). The LOHS (days) decreased from 15.9 (2000-2004) to 15.7 (2005-2009) to 14.5 (2010-2013) (p < 0.001). Total and per patient hospital costs increased from 2000 to 2011, and then decreased by the impact of the economic crisis. CONCLUSIONS: Sepsis has caused an increasing burden in terms of hospital admission, deaths, and costs in the Spanish public health system during the twenty-first century, but the incidence and mortality seemed to stabilize in 2010-2013. Moreover, there was a significant decrease in LOHS in 2010-2013 and a decline in hospital costs after 2011.

Abacavir Induces Arterial Thrombosis in a Murine Model.

Background: The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods: The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results: Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was nonexistent in P2X7 knockout mice. The effects of abacavir were similar to those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects. Conclusion: Abacavir promotes arterial thrombosis through interference with purinergic signaling, suggesting a possible biological mechanism for the clinical association of abacavir with cardiovascular diseases.

Giant parathyroid adenoma: differential aspects compared to parathyroid carcinoma.

The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually exceeds these dimensions and are associated with a severe PHPT. However, giant PA (GPA), which is defined as those larger than 3 g, has been documented. Those may be associated with very high levels of PTH and calcium. In these cases, their differentiation before and after surgery with PC is very difficult. We present a case of severe PHPT associated with a large parathyroid lesion, and we discuss the differential aspects between the GPA and PC. LEARNING POINTS: In parathyroid lesions larger than 2 cm, the differential diagnosis between GPA and PC should be considered.Pre and postsurgical differentiation between GPA and PC is difficult; however, there are clinical, analytical and radiographic characteristics that may be useful.The depth/width ratio larger or smaller than 1 seems to be the most discriminatory ultrasound parameter for the differential diagnosis.Loss of staining for parafibromin has a specificity of 99% for the diagnosis of PC.The simultaneous presence of several histological characteristics, according to the classification of Schantz and Castleman, is frequent in PC and rare in GPA.

SIADH secundario a adenocarcinoma seroso de ovario tratado con tolvaptán / SIADH secondary to serous ovarian adenocarcinoma treated with tolvaptan

La hiponatremia es la alteración electrolítica más frecuente en el medio hospitalario, y en un 30% de los casos se debe a un síndrome de secreción inapropiada de vasopresina (SIADH). El SIADH está descrito como cuadro paraneoplásico endocrinológico en múltiples tumores, entre los que excepcionalmente se encuentra el de ovario y las neoplasias ginecológicas en general. Presentamos un caso de SIADH paraneoplásico por un citoadenocarcinoma seroso de ovario de alto grado, estadio IV. Se trata del primer caso de SIADH crónico por cáncer de ovario tratado con Tolvaptán. En el presente caso el objetivo de eunatremia se alcanzó con una dosis baja de acuarético, lo que apoya la elevada sensibilidad, ya previamente documentada, de los SIADH tumorales al tratamiento con Tolvaptán.

Hyponatremia is the most common electrolyte disturbance in hospitals, and 30% of cases are due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). SIADH is described as an endocrine paraneoplastic syndrome in multiple tumors including, ovary and gynecological malignancies in general, although these are exceptional. We report a case of paraneoplastic SIADH for high-grade serous ovarian cystoadenocarcinoma stage IV. This is the first case of chronic SIADH for ovarian cancer treated with Tolvaptan. In this case the target of eunatremia was reached with a low dose of aquaretic, which supports the high sensitivity, as previously documented, of paraneoplasic SIADH to Tolvaptan.

Programa de optimización del uso de antimicrobianos (PROA). Experiencia en un hospital secundario / A program for optimizing the use of antimicrobials (PROA): experience in a regional hospital

Introducción. Los programas de optimización del uso de antimicrobianos (PROA) son programas multidisciplinares que surgen ante el aumento de los microorganismos resistentes a los antimicrobianos, con el objetivo de mejorar los resultados clínicos, minimizar efectos adversos y reducir el gasto derivado de su uso. Se describe la implantación de este programa en un hospital general de 128 camas y sus resultados tras 6 meses. Material y métodos. Estudio prospectivo de intervención cuasi-experimental con grupo de control histórico con el objetivo de evaluar el impacto de un programa PROA consistente en un modelo de intervención no restrictivo, de ayuda a la prescripción con intervención directa y bidireccional. La base es una auditoría de optimización del uso de antimicrobianos con recomendaciones personalizadas no impositivas y el uso de tecnologías de información aplicadas a este entorno. Describimos el impacto en el consumo y gasto farmacéutico, coste por proceso, estancia media y porcentaje de reingresos. Resultados. Se han realizado 307 auditorías. En el 65,8% de los tratamientos se suspendieron entre el séptimo y décimo día. Los principales motivos de interrupción son tratamiento completado (43,6%) y ausencia de indicación (14,7 %). La reducción del gasto farmacéutico fue del 8,59% (P=0,049) y del 5,61% del consumo en DDD/100 estancias (P=0,180). Los costes por proceso en cirugía general se han reducido un 3,14% (p=0,000). Conclusión. Los resultados obtenidos avalan la eficiencia de estos programas en hospitales de pequeño tamaño con recursos limitados (AU)

Introduction. Programs for optimizing the use of antibiotics (PROA) or antimicrobial stewardship programs are multidisciplinary programs developed in response to the increase of antibiotic resistant bacteria, the objective of which are to improve clinical results, to minimize adverse events and to reduce costs associated with the use of antimicrobials. The implementation of a PROA program in a 128-bed general hospital and the results obtained at 6 months are here reported. Methods. An intervention quasi-experimental study with historical control group was designed with the objective of assessing the impact of a PROA program with a non-restrictive intervention model to help prescription, with a direct and bidirectional intervention. The basis of the program is an optimization audit of the use of antimicrobials with not imposed personalized recommendations and the use of information technologies applied to this setting. The impact on the pharmaceutical consumption and costs, cost per process, mean hospital stay, percentage of readmissions to the hospital are described. Results. A total of 307 audits were performed. In 65.8% of cases, treatment was discontinued between the 7th and the 10th day. The main reasons of treatment discontinuation were completeness of treatment (43.6%) and lack of indication (14.7%). The reduction of pharmaceutical expenditure was 8.59% (P = 0.049) and 5.61% of the consumption in DDD/100 stays (P=0.180). The costs by processes in general surgery showed a 3.14% decrease (p=0.000). Conclusion. The results obtained support the efficiency of these programs in small size hospitals with limited resources (AU)

Rhabdomyolysis secondary to quetiapine.

Quetiapine is one of the drugs used most in current Psychiatry due to its therapeutic efficiency and clinical safety. We report the case of a 26-year-old male patient with severe mental retardation due to Y-chromosome partial deletion who initiated treatment with quetiapine for the control of his aggressiveness, and who developed severe rhabdomyolysis two weeks later. In spite of the confirmed clinical safety of quetiapine, doctors must monitor the appearance of rare but serious adverse effects as that presented in this clinical case.

Rabdomiólisis secundaria a tratamiento con quetiapina / Rhabdomyolysis secondary to quetiapine

La quetiapina es uno de los fármacos más empleados en la Psiquiatría actual, debido a su eficacia terapéutica y seguridad clínica. Presentamos el caso de un paciente de 26años, con retraso mental grave debido a deleción parcial del cromosoma Y, que inicia tratamiento con quetiapina parael control de su agresividad, y que desarrolla a las 2 semanas una rabdomiólisis severa. A pesar de la seguridad clínica contrastada de la quetiapina, los médicos deben vigilar laaparición de raros pero graves efectos adversos como el presentado en este caso clínico (AU)

Quetiapine is one of the most used drugs in current Psychiatry, due to its therapeutic efficiency and clinical safety. We report the case of a 26-year-old patient, serious mental retardation due to Y-chromosome partial deletion, that initiates treatment with quetiapine for the control of his aggressiveness, and that develops severe rhabdomyolysis two weeks later. In spite of the clinical safety confirmed of quetiapine, doctors must monitor the appearance of rare but serious adverse effects as the presented one in this clinical case (AU)