Herramientas de abordaje ante la consulta de diversidad sexual en la infancia y adolescencia

La identidad de género se define como la autopercepción de género, que puede o no corresponder con el sexo asignado al nacer. Aquellos niños que poseen una identidad de género que no coincide con el sexo biológico, son denominados "no conformes con su género", con "variante de género" o "transgénero". Existen evidencias crecientes que el cuidado y contención adecuados de estos niños/as y adolescentes pueden disminuir el daño y mejorar significativamente su inserción social y su calidad de vida. El objetivo de este artículo es proporcionar definiciones y orientaciones prácticas para el tratamiento endocrinológico de niños/as y adolescentes con disconformidad de género. Éste surge en respuesta a una demanda creciente en los últimos años. Se efectuó revisión bibliográfica basada en el análisis de las guías y publicaciones nacionales e internacionales, evaluando la aplicabilidad en nuestro medio y reforzando el seguimiento inter y transdisciplinario. Existe en la Argentina un marco legal encuadrado en la Ley 26.743 de "Identidad de Género" y a nivel internacional los Principios de Yogyakarta. El acompañamiento temprano de estos niños/as y adolescentes, en caso de persistencia o intensificación de la disconformidad de género, podría derivar en tratamientos orientados a disminuir las posibles comorbilidades asociadas, así como lograr cambios antropométricos, físicos y metabólicos, que deben ser conocidos y manejados por equipos transdisciplinarios en centros de referencia.

Gender identity is defined as gender self- perception, which may or may not correspond to the sex assigned at birth. Those children whose gender identity is different to the biological sex, are called "gender nonconforming," "gender diverse, or "transgender ". There is growing evidence that with supportive, increasing visibility and social acceptance of gender diversity, their social integration and quality of life can be significantly improved. The objective of this article is to provide definitions and practical guidelines for the endocrinological treatment of children and adolescents with gender disconformity. It arises in response to a growing demand in recent years. A bibliographic review was carried out, based on the analysis of national and international guides and publications, evaluating inter and multidisciplinary follow up and applicability among us. There is a legal framework in Argentina, supported by the law 26.743, about "Gender identity", and an internationally one, expressed in the Yogyakarta Principles. In case of persistence or intensification of gender disconformity, with early support and treatment, harms could be meliorated and the possible associated comorbidities can be significantly improved. Anthropometric, physical and metabolic changes should be known and managed by multidisciplinary teams in reference centers

Commentary on 50 years of research at the NBRL, Boston, Massachusetts.

Research at the NBRL, Boston, MA over the past 50 years assessed the survival and function of RBC and platelets and the function of plasma clotting proteins. Liquid preserved RBC can be stored at 4 °C for only 2 weeks to maintain a 24-hour posttransfusion survival value of 75%, moderately impaired oxygen transport function after transfusion, exert a hemostatic effect, and increase the plasma volume. Liquid preserved platelets can be stored at room temperature with agitation for only 2 days to have acceptable in vivo survival 2 hours following transfusion, normal lifespan, and a hemostatic effect to reduce the bleeding time in thrombocytopenic patients. RBCs frozen with 40% W/V glycerol at -80 °C for at least 10 years, thawed, and deglycerolized in the Haemonetics ACP215 can be stored in Nutricel at 4 °C for 2 weeks with a 24-hour posttransfusion survival of 75%, moderately impaired oxygen transport function after transfusion, exert a hemostatic effect and increase the plasma volume. Leukoreduced single donor platelets treated with 6% DMSO, the supernatant DMSO removed prior to freezing at -80 °C for 2 years, thawed, and diluted with 0.9% NaCl or AB plasma have a bimodal population of platelets: one population has reduced in vivo survival, but increased hemostatic effect and the other has normal in vivo survival. AB plasma can be stored at -80 °C for at least 14 years, thawed, and stored at 4 °C for 24 hours with acceptable in vitro function of clotting proteins. The data reported by the NBRL, Boston, Mass. over the past 50 years and the 15-year experience by the Netherlands military now recommend that FDA, ARC, HHS and DOD should support the use of universal donor frozen group O Rh positive and group O Rh negative RBC, frozen group O platelets and frozen AB plasma from male donors. The frozen blood products will eliminate the severe adverse events of mortality and morbidity associated with the current FDA approved red blood cell products, platelet products, and plasma.

The unrecognized effects of the volume and composition of the resuscitation fluid used during the administration of blood products.

BACKGROUND: Recent publications have reported the severe adverse events associated with blood products but have not considered the effect of the volume and composition of the resuscitative fluids infused with the blood products. METHODS: Injury leads to cellular reaction characterized by insulin resistance during which glucose cannot enter muscle and fat cells. In all cells, mitochondrial pyruvate dehydrogenase activity is decreased during insulin deficiency leaving cells deficient in substrates needed to power the Krebs cycle and make ATP. RESULTS: d-ß-Hydroxybutyrate, a normal ketone body metabolite, enters cells on the monocarboxylate transport mimicking the action of insulin and bypassing the enzymatic block at PDH. Metabolism of ketone bodies increases efficiency of mitochondrial energy production and cellular ATP level. CONCLUSION: Infusion of 250 ml of 600 mM Na d-ß-hydroxybutyrate solution, with the same osmotic strength as the hypertonic NaCl solution currently being used, would correct insulin resistance, provide energy substrates for cells to produce ATP, correct the tendency of injured tissue to swell due to decreased energy of ionic gradients and correct acidosis observed in hemorrhage.

The mitochondrial permeability transition pore provides a key to the diagnosis and treatment of traumatic brain injury.

The pathological consequences of traumatic head injury result largely from the opening of the mitochondrial permeability transition pore (mPTP). The mPTP opens due to a decrease in brain phosphorylation energy resulting in a further decrease in brain ATP production and a measurable increase in brain heat generation and temperature. The increase in brain temperature can be measured transcranially by near infrared spectroscopy which can be used to diagnose traumatic brain injury (TBI) and to monitor treatment. Effective therapy of TBI can be achieved by closure of the mPTP by administration of cyclosporine A or by oral administration of ketone body esters. While ketosis has previously been known to prevent damage from TBI, the availability of oral ketone esters presents the first practical modality of achieving therapeutic levels of ketone bodies.

mRDH bandage for surgery and trauma: data summary and comparative review.

BACKGROUND: Bleeding often poses significant life-threatening situations to surgeons. After trauma, a one-third of civilian casualties and one-half of combat casualties die as a result of exsanguination. Recent advances have provided promising new hemostatic dressings that are applied directly to severely bleeding wounds in the pre-hospital period. METHODS: The modified Rapid Deployment Hemostat (mRDH) trauma/surgery bandage, containing fully acetylated, diatom-derived, poly-N-acetyl-glucosamine fibers, has a unique multifactorial hemostatic action that incorporates vasoconstriction, erythrocyte agglutination, and platelet and RBC activation. RESULTS: Animal studies have shown that the mRDH bandage quickly and completely stops both venous and arterial bleeding, even in the presence of a coagulopathy. A prospective study in humans is in accord with these findings. CONCLUSION: The mRDH trauma/surgery bandage was able to increase survival of patients after high-grade liver trauma with an associated coagulopathy. Additional clinical studies support this result.

Poly-N-acetyl glucosamine fibers accelerate hemostasis in patients treated with antiplatelet drugs.

BACKGROUND: Nanofibers consisting of poly-N-acetyl glucosamine (pGlcNAc), as the functional component of products for surface hemostasis, have been shown to activate platelets and thereby the clotting mechanism. The nanofiber-activated platelets provide a catalytic surface for acceleration of the intrinsic coagulation cascade, thrombin generation, and fibrin polymerization. METHODS: Thromboelastographic analysis was undertaken to study the role of the pGlcNAc nanofibers in platelet activation and acceleration of fibrin polymerization. Thromboelastographic studies were performed without added activators of coagulation. RESULTS: The pGlcNAc nanofibers were found to accelerate fibrin polymerization in whole blood and platelet-rich plasma. Treatment with eptifibatide (an inhibitor of the platelet GPIIbIIIa receptor) and corn trypsin inhibitor inhibited clotting of whole blood and platelet-rich plasma. The inhibition was reversed by treatment with pGlcNAc nanofibers. Inhibition was not observed after treatment with aspirin alone, MRS2359 (platelet ADP receptor inhibitor), or by a combination of aspirin and MRS2359. The pGlcNAc nanofibers accelerate clotting in normal blood treated with aspirin and MRS2359. Clopidogrel (Plavix) and aspirin did not affect the kinetics of pGlcNAc-mediated fibrin polymerization in blood from patients treated with antiplatelet drugs compared with nontreated blood. CONCLUSIONS: These results provide evidence that pGlcNAc nanofibers activate platelets and accelerate the clotting of blood, and on how best to achieve surface hemostasis when patients are coagulopathic because of shock and/or to treatment with antiplatelet drugs.

Poly-N-acetyl glucosamine fibers induce angiogenesis in ADP inhibitor-treated diabetic mice.

BACKGROUND: It has been previously demonstrated that short-fiber poly-N-acetyl-glucosamine (sNAG) nanofibers specifically interact with platelets, are hemostatic, and stimulate diabetic wound healing by activating angiogenesis, cell proliferation, and reepithelialization. Platelets play a significant physiologic role in wound healing. The influence of altered platelet function by treatment with the ADP inhibitor Clopidogrel (CL) on wound healing and the ability of sNAG to repair wounds in diabetic mice treated with CL were studied. METHODS: Dorsal 1 cm2 skin wounds were excised on genetically diabetic 8-week to 12-week-old, Lep/r-db/db male mice, and wound healing kinetics were determined. Microscopic analysis was performed for angiogenesis (PECAM-1) and cell proliferation (Ki67). Mice were either treated with CL (P2Y12 ADP receptor antagonist, CL) or saline solution (NT). CL wounds were also treated with either a single application of topical sNAG (CL-sNAG) or were left untreated (CL-NT). RESULTS: CL treatment did not alter wound healing kinetics, while sNAG induced faster wound closure in CL-treated mice compared with controls. CL treatment of diabetic mice caused an augmentation of cell proliferation and reduced angiogenesis compared with nontreated wounds. However, sNAG reversed the effects of CL on angiogenesis and partially reversed the effect on cell proliferation in the wound beds. The sNAG-treated wounds in CL-treated mice showed higher levels of cell proliferation and not did inhibit angiogenesis. CONCLUSIONS: CL treatment of diabetic mice decreased angiogenesis and increased cell proliferation in wounds but did not influence macroscopic wound healing kinetics. sNAG treatment did not inhibit angiogenesis in CL-treated mice and induced faster wound closure; sNAG technology is a promising strategy to facilitate the healing of complex bleeding wounds in CL-treated diabetic patients.

Poly-N-acetyl glucosamine fibers are synergistic with vacuum-assisted closure in augmenting the healing response of diabetic mice.

BACKGROUND: Vacuum-assisted closure (VAC) has become the preferred modality to treat many complex wounds but could be further improved by methods that minimize bleeding and facilitate wound epithelialization. Short fiber poly-N-acetyl glucosamine nanofibers (sNAG) are effective hemostatic agents that activate platelets and facilitate wound epithelialization. We hypothesized that sNAG used in combination with the VAC device could be synergistic in promoting wound healing while minimizing the risk of bleeding. METHODS: Membranes consisting entirely of sNAG nanofibers were applied immediately to dorsal excisional wounds of db/db mice followed by application of the VAC device. Wound healing kinetics, angiogenesis, and wound-related growth factor expression were measured. RESULTS: The application of sNAG membranes to wounds 24 hours before application of the VAC device was associated with a significant activation of wounds (expression of PDGF, TGFß, EGF), superior granulation tissue formation rich in Collagen I as well as superior wound epithelialization (8.6% ± 0.3% vs. 1.8% ± 1.1% of initial wound size) and wound contraction. CONCLUSIONS: The application of sNAG fiber-containing membranes before the application of the polyurethane foam interface of VAC devices leads to superior healing in db/db mice and represents a promising wound healing adjunct that can also reduce the risk of bleeding complications.

An approach to prevent the severe adverse events associated with transfusion of FDA-approved blood products.

There have been several retrospective studies reporting severe adverse events of mortality and morbidity associated with blood transfusions. Mortality and morbidity associated with posttransfusion infection, transfusion related acute lung injury (TRALI), and systemic inflammatory response syndrome (SIRS) have been reported in patients undergoing cardiac surgery, after massive transfusions for severe traumatic injuries, and after transfusions for elective and emergency indications. After 35 days of storage at 4 degrees C in additive solutions, RBC have 24-h posttransfusion survival values of 75% but do not function satisfactorily. For RBC to function satisfactorily shortly after transfusion, they should be stored at 4 degrees C for no more than 2 weeks. Yet while the FDA requires a 24-h posttransfusion survival value of 75%, there is no requirement for the function of the transfused RBC. It has been shown that red blood cells that circulate and function immediately or shortly after transfusion exert a very important hemostatic effect to reduce the bleeding time and nonsurgical blood loss in anemic and thrombocytopenic patients. Greater restoration of hemostasis is seen with viable and functional RBC transfusions than with platelets or plasma even though the platelets and plasma proteins may have satisfactory viability and function. The length of storage of the blood products affects their survival and function and the transfusion of nonviable compatible RBC, antibodies to granulocytes and WBC HLA antigens and biologically active substances affects the patient's clinical outcome. One of the easiest ways to prevent the severe adverse events that have been observed is to ensure that the transfused blood products survive and function at an optimum level and that the levels of antibodies to granulocytes and WBC HLA antigens and biologically active substances are eliminated or reduced. The best way to ensure this is to store liquid-preserved leukoreduced human red blood cells at 4 degrees C in additive solutions for no more than 2 weeks and leukoreduced platelets at room temperature for no more than 2 days. These liquid-preserved blood products can be used in conjunction with frozen RBC, platelets, and plasma stored in -80 degrees C mechanical freezers and will avoid the need for fresh whole blood and prevent the severe adverse events associated with the transfusion of blood products.

Quiescent platelets stimulate angiogenesis and diabetic wound repair.

INTRODUCTION: Platelets partake in hemostasis, wound healing, and tumor growth. Although platelet-rich-plasma (PRP) has been used in surgery for several years, its mechanism of action and application methods are still poorly characterized. MATERIALS AND METHODS: A single unit of human platelets obtained by plateletpheresis was diluted in plasma and divided into three equal volumes. One volume was stored at room temperature as fresh platelets (RT), another volume was frozen by storage at -80 degrees C (FZ), and the third volume was frozen at -80 degrees C with 6% DMSO (FZ6). Plasma (PL) was used as control. Using flow cytometry, platelets were tested for platelet glycoprotein GPIb and annexin V binding, as survival and activation markers, respectively. Hemostatic function was assessed by thromboelastometry. In vivo, platelets were topically applied on 1 cm,(2) full-thickness wounds on db/db mice (n = 10/group) and healing was staged microscopically and macroscopically. RESULTS: All platelet preparations showed hemostatic ability. RT platelets were GPIb positive (nonactivated-quiescent platelets) and stimulated angiogenesis by threefold, and cell proliferation by fourfold in vivo. FZ platelets were positive for annexin V, indicating activated platelets and, in vivo, increased only wound granulation. FZ6 platelets contained 30% nonactivated-quiescent and 50% activated platelets and stimulated granulation, angiogenesis, cell proliferation, and promoted re-epithelialization in vivo. CONCLUSIONS: Platelets showed distinct mechanisms to induce hemostasis and wound healing. Quiescent platelets are required to induce angiogenesis in vivo. Platelets stored at room temperature and frozen with 6% DMSO and stored at -80 degrees C achieved optimal wound healing in diabetic mice.

Role of nitric oxide in the prevention of severe adverse events associated with blood products.

The reduction in vitro of nitric oxide binding to the globin portion of hemoglobin (SNOHb) in fresh and liquid preserved red blood cells has been reported to be responsible for the severe adverse events (SAEs) associated with red blood cell transfusion. No in vivo data were reported that the reduction in SNOHb in red blood cells following transfusion was irreversible. In addition, no clinical data were reported that the reduction in SNOHb in red blood cells produced severe adverse events (SAEs) in recipients.

Severe adverse events associated with hemoglobin based oxygen carriers: role of resuscitative fluids and liquid preserved RBC.

Severe adverse events have been observed following the infusion of hemoglobin based oxygen carriers in patients subjected to elective orthopedic procedures, cardiopulmonary bypass surgery, and vascular surgical procedures. Along with all three of the hemoglobin based oxygen carriers, the patients received Ringer's D,L-lactate as the resuscitative fluid, Ringer's d,l-lactate in the excipient medium for the stroma free hemoglobin, and liquid preserved red blood cells that had been stored at 4 degrees C for longer than 2 weeks. The Ringer's d,l-lactate solution has been shown to be toxic in both animals and patients. The current formulation of Ringer's lactate contains only the l-isomer which has been shown in animals to be less toxic than the d-isomer of lactate. In a recent publication morbidity and mortality have been reported associated with the length of storage of red blood cells at 4 degrees C in patients subjected to reoperative cardiac surgery. Current clinical studies to assess the safety and therapeutic effectiveness of a hemoglobin based oxygen carrier (HBOC) must consider the effects of the composition of the resuscitation solution (Ringer's L-lactate), the composition of the excipient medium (Ringer's L-lactate or 0.9% NaCl) for the hemoglobin based oxygen carrier, and the length of storage of the liquid preserved red blood cells infused with the hemoglobin based oxygen carrier.

Non-classical processes in surface hemostasis: mechanisms for the poly-N-acetyl glucosamine-induced alteration of red blood cell morphology and surface prothrombogenicity.

It is well established that platelets and the intrinsic plasma coagulation pathway can be activated when blood contacts artificial surfaces. Experiments were performed to assess the effect of hemostatic poly-N-acetyl glucosamine (pGlcNAc) nanofibers on red blood cells. The pGlcNAc nanofibers, isolated from a marine diatom, interact with red blood cells (RBCs) to produce stomatocytes. The stomatocytes could be converted to echinocytes by treatment with echinocytic reagents, as measured by electron microscopy. Electrophoretic and Western blot analysis of RBC surface proteins demonstrated that pGlcNAc fibers were bound to band 3 of the RBC. An important and unique result of the interaction of RBCs with pGlcNAc fibers was the activation of the intrinsic coagulation cascade. This prothrombotic effect was associated with the presentation of phosphatidylserine on the outer layer of the surface membrane of nanofiber bound RBCs. The results demonstrate that RBCs can play a direct and important role in achieving surface hemostasis by accelerating the generation of thrombin, and add to the growing body of evidence that RBCs can strongly interact with hemostatic systems.