Animal models for neurotoxicity assessment in cardiac arrest / Modelos animales para evaluar la neurotoxicidad en el paro cardíaco

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Principales modelos experimentales de traumatismo craneoencefálico: de la preclínica a los modelos in vitro / Experimental models in traumatic brain injury: from animal models to in vitro assays

El traumatismo craneoencefálico (TCE) es una de las patologías más importantes en la actualidad, ya que afecta a un alto porcentaje de individuos de todas las edades. A pesar de los avances en el campo del diagnóstico, la monitorización y el tratamiento del TCE, quedan importantes cuestiones sin resolver alrededor de la fisiopatología de este tipo de traumatismo. Con el fin de profundizar en dicho conocimiento y poder evaluar y aplicar un posible tratamiento que resulte eficaz para estos pacientes, se han desarrollado diferentes modelos experimentales que simulan los mecanismos de acción y el cuadro clínico del TCE. A su vez, cada modelo representa un determinado tipo de traumatismo y evalúa un aspecto concreto de la cascada fisiopatológica desencadenada tras el TCE. El objetivo de este trabajo es detallar los principales modelos experimentales que abordan la lesión cerebral tras un TCE, así como su potencial traslación a la práctica clínica diaria

Traumatic brain Injury (TBI) is a major public healthcare concern, affecting people of all ages. Despite advances in the diagnosis, monitoring and clinical management of TBI, many unresolved questions remain regarding its physiopathology. In an attempt to understand the pathological features of TBI and to evaluate single potential therapeutic strategies, various animal models have been developed to simulate the mechanisms of action and the clinical manifestations of TBI patients. In turn, each model represents a specific type of trauma and evaluates a specific physiopathological aspect of the cascade triggered as a result of TBI. This review describes the main experimental models currently available referred to TBI and their possible application to the clinical setting

Experimental models in traumatic brain injury: from animal models to in vitro assays. / Principales modelos experimentales de traumatismo craneoencefálico: de la preclínica a los modelos in vitro.

Traumatic brain Injury (TBI) is a major public healthcare concern, affecting people of all ages. Despite advances in the diagnosis, monitoring and clinical management of TBI, many unresolved questions remain regarding its physiopathology. In an attempt to understand the pathological features of TBI and to evaluate single potential therapeutic strategies, various animal models have been developed to simulate the mechanisms of action and the clinical manifestations of TBI patients. In turn, each model represents a specific type of trauma and evaluates a specific physiopathological aspect of the cascade triggered as a result of TBI. This review describes the main experimental models currently available referred to TBI and their possible application to the clinical setting.

Standardization of the homogeneous mobility shift assay protocol for evaluation of anti-infliximab antibodies. Application of the method to Crohn's disease patients treated with infliximab.

BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug.

Breast sharing: New perspectives on an old method.

BACKGROUND: Many techniques have been described for breast reconstruction after mastectomy throughout the decades. In many cases, with excess tissue being discarded, a significant reduction of the contralateral breast was needed for symmetry. Described by Marshall as a one-staged, autologous, non-microsurgical breast reconstruction technique, this method was used in perforator flaps as a breast-sharing technique. METHODS: Between June 2011 and January 2014, the breast-sharing technique was performed in seven patients with simple mastectomy, delayed breast reconstruction, and willingness for autologous non-microsurgical breast reconstruction. All the participants in this study received preoperative oncological screening with ultrasound, magnetic resonance imaging, or mammography, which revealed the absence of pathologic imaging in the donor breast. RESULTS: The experiences of seven patients who underwent breast reconstruction surgery through breast-sharing technique are presented. Due to venous congestion, one of the patients (14%) suffered major complications with total loss of the flap. A total of four patients (57%) incurred minor complications with little to no repercussions on the final outcome. The functional and aesthetic outcomes were very satisfactory, and only one patient required a second touch-up surgery for lipofilling due to unsatisfactory breast volume. Regular follow-ups were done by the oncologist with no recurrences found up to the present. CONCLUSIONS: Using contralateral breast as the donor site, this article presents the first case series for one-stage mammarian reconstruction. With some complications but good aesthetic outcomes, this method has been shown as another available method for breast reconstruction in patients with hypertrophic and ptotic breast.

Update of the Atlanta Classification of severity of acute pancreatitis: should a moderate category be included?

BACKGROUND: Persistent and multiple organ failure (POF and MOF) are predictive of death in acute pancreatitis (AP). Local complications without organ failure are associated with morbidity but a low risk of mortality. AIM: To design a three-category classification of AP severity and to compare it with the Atlanta Classification (AC) in terms of morbidity and mortality. METHOD: Severe AP was defined as death, POF (>48 h) or MOF. Moderate AP was defined as the presence of acute collections and/or pancreatic necrosis. Mild AP was defined by exclusion. We compared this classification with AC in 144 episodes of AP. RESULTS: In the three-category classification, severe AP was associated with significantly more frequent intensive care unit admission, invasive treatment and mortality than moderate and mild AP (p < 0.01). Severe AP patients required longer hospital stay and more nutritional support than mild AP patients (p < 0.01). Patients with moderate AP had significantly longer hospital stay and more need for nutritional support than patients with mild AP (p < 0.01). Five patients died, all of them with MOF and/or POF. CONCLUSIONS: A three-category classification distinguishes three homogeneous groups of severity.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

OBJECTIVE: to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. MATERIAL AND METHODS: prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. RESULTS: median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). CONCLUSION: MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

Valoración del pronóstico a corto y largo plazo de pacientes con cirrosis y hemorragia digestiva por hipertensión portal / Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding

Objetivo: evaluar la eficacia de los diferentes indicadores pronósticosde supervivencia a corto y largo plazo en pacientes concirrosis y hemorragia digestiva alta por hipertensión portal (HTP).Material y métodos: calculamos los indicadores pronósticosen una cohorte de 201 pacientes con cirrosis y hemorragia digestivapor HTP ingresados en el Hospital General Universitario deAlicante. Las variables a estudio fueron: edad, sexo, etiología de lacirrosis, hallazgos endoscópicos, episodios previos de hemorragiadigestiva por HTP. Infección por el virus de la inmunodeficienciahumana (VIH), hepatocarcinoma (HCC), infección bacteriana duranteel episodio de hemorragia digestiva y clasificación de Child-Turcotte-Pugh (CTP) y el modelo para enfermedades terminalesdel hígado (MELD score) calculados dentro de las primeras 24 horasdel inicio de la hemorragia. Los pacientes fueron seguidos almenos 6 meses hasta su muerte, trasplante hepático o final del seguimiento.Resultados: la mediana de seguimiento fue de 66,85 semanas(rango 0-432,4). La mortalidad a las 6 semanas, 3 meses, 12meses y 36 meses fue de 22,9, 24,9, 34,3 39,8%, respectivamente.La edad ≥ 65 años, la presencia de HCC, una clasificaciónde CTP ≥ 10 y un MELD score ≥ 18 fueron las variables asociadasa la mortalidad en el estudio multivariante. La precisión delMELD score como predictor de mortalidad a las 6 semanas, 3meses, 12 meses y 36 meses fue superior a la de la clasificaciónde CTP (valor c-estadístico: 6 semanas MELD 0,804, CTP 0,762;3 meses MELD 0,794, CTP 0,760; 12 meses MELD 0,766, CTP0,741; 36 meses MELD 0,737, CTP 0,717).Conclusión: el MELD score y la clasificación de CTP, juntocon la edad y la presencia de HCC, son marcadores útiles en lavaloración pronóstica de supervivencia a corto y largo plazo de lospaciente con cirrosis y hemorragia digestiva por HTP(AU)

Objective: to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. Material and methods: prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. Results: median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age ≥ 65 years, presence of HCC, CTP score ≥ 10, and MELD score ≥ 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). Conclusion: MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding(AU)

Optical properties of photonic crystal fiber with integral micron-sized Ge wire.

Using a selective hole closure technique, individual hollow channels in silica-air photonic crystal fibers are filled with pure Ge by pumping in molten material at high pressure. The smallest channels filled so far are 600 nm in diameter, which is 10x smaller than in previous work. Electrical conductivity and micro-Raman measurements indicate that the resulting cm-long wires have a high degree of crystallinity. Optical transmission spectra are measured in a sample with a single wire placed adjacent to the core of an endlessly single-mode photonic crystal fiber. This renders the fiber birefringent, as well as causing strongly polarization-dependent transmission losses, with extinction ratios as high as 30 dB in the visible. In the IR, anti-crossings between the glass-core mode and resonances on the high index Ge wire create a series of clear dips in the spectrum transmitted through the fiber. The measurements agree closely with the results of finite-element simulations in which the wavelength dependence of the dielectric constants is taken fully into account. A toy model based on a multilayer structure is used to help interpret the results. Finally, the temperature dependence of the anti-crossing wavelengths is measured, the preliminary results suggesting that the structure might form the basis of a compact optical thermometer. Since Ge provides electrical conductance together with low-loss guidance in the mid-IR, Ge-filled PCF seems likely to lead to new kinds of in-fiber detector and sensor, as well as having potential uses in ultra-low-threshold nonlinear optical devices.

Supraclavicular bilobed fasciocutaneous flap for postburn cervical contractures.

Anterior cervical contractures after burn are a common problem in the treatment of sequelae in burnt patients. The contracture itself and the hypertrophic scarring can cause functional limitation and aesthetic disfigurement. As a consequence, the reconstruction of this area is a challenge to surgeons that must choose a procedure, which improves functionality and aesthetic appearance in addition to reversing the contracture, the surgical goal of avoiding a new scar band over time is added. We present three patients with moderate (grade II) cervical contractures caused by suicide attempt and reconstructed by means of a bilobed flap based on the supraclavicular axis with the purpose of avoiding grafts in the donor area and performing it in a single procedure. This flap is useful and reliable for reconstruction of defects caused by cervical scars in non-collaborative and psychologically unstable patients. The anatomy, surgical procedure and results in our series are presented in this article.

Versatility of the pedicled thoracodorsal artery perforator (TDAP) flap in soft tissue reconstruction.

For the last decades, the latissimus dorsi skin-muscle flap has contributed to the efficient reconstruction of the loss of skin cover (especially in breast surgery) and in long-distance tissue defects. Unfortunately, the nonuse of such an important muscle as the latissimus dorsi for the patient, as well as the resulting thickness of the flap after reconstruction, has turned it into a second choice flap. However, this flap is still indicated in the reconstruction of areas which need a great amount of cutaneous and muscular tissue. The appearance of the perforator flaps and, specifically, thoracodorsal artery perforator (TDAP) flap, has meant a radical change in relation to lower morbidity of the donor site, thus highly ranking the use of these flaps in the reconstruction for similar defects. The aim of this publication is to present our experience with the pedicled TDAP flap in a series of 17 different cases. Of those, there were 14 cases of mammary reconstruction after sparing surgery, 2 cases of axillary reconstruction following severe recurrent hidradenitis, and a case of extensive substance loss in a patient's upper limb following a severe crush injury.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in patients with cirrhosis and variceal bleeding significantly improves the control of the bleeding episode, and hemodynamic data have shown that a dosage of 500 mg/h allows a more marked reduction of portal pressure versus the usual dosage of 250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved outcome. METHODS: sixty-two patients with variceal bleeding were included in the study. Patients were randomized to receive the usual dosage of SMT (group I: 250 mg/h), or a double dosage (group II: 500 mg/h), together with emergency endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was similar in both groups of patients. Early rebleeding was less frequent in patients receiving double vs. single dosage of SMT (p = 0.06). When considering patients with advanced liver disease (Child-Pugh B or C) early rebleeding was significantly less frequent in patients receiving the 500 mg/h dose of SMT (39 vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h) in association with emergency sclerotherapy in patients with cirrhosis and esophageal hemorrhage significantly decreases the rate of early rebleeding in patients with more advanced stages of liver disease.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial

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Background: the association of somatostatin (SMT) with endoscopictherapy in patients with cirrhosis and variceal bleedingsignificantly improves the control of the bleeding episode, and hemodynamicdata have shown that a dosage of 500 µg/h allows amore marked reduction of portal pressure versus the usual dosageof 250 µg/h.Aim: to assess if the 500 µg/h dosage is associated with animproved outcome.Methods: sixty-two patients with variceal bleeding were includedin the study. Patients were randomized to receive the usualdosage of SMT (group I: 250 µg/h), or a double dosage (group II:500 µg/h), together with emergency endoscopic sclerotherapy.Results: the control of the bleeding episode was similar inboth groups of patients. Early rebleeding was less frequent in patientsreceiving double vs. single dosage of SMT (p = 0.06). Whenconsidering patients with advanced liver disease (Child-Pugh B orC) early rebleeding was significantly less frequent in patients receivingthe 500 µg/h dose of SMT (39 vs. 13%, p = 0.03).Conclusions: the perfusion of higher doses of SMT (500µg/h) in association with emergency sclerotherapy in patientswith cirrhosis and esophageal hemorrhage significantly decreasesthe rate of early rebleeding in patients with more advanced stagesof liver disease

Detection and identification of bacterial DNA in serum from patients with acute pancreatitis.

BACKGROUND AND AIMS: Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of bacterial DNA in biological fluids, and we aimed to detect bacterial DNA in patients with acute pancreatitis, as molecular evidences of bacterial translocation. METHODS: Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species. RESULTS: Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of bacterial DNA. CONCLUSION: Detection of gram negative bacteria derived bacterial DNA in our series supports the contention that bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of infection.

[Primary linitis plastica of the rectum]. / Linitis plástica de recto primaria.

Linitis plastica of the rectum is an uncommon entity that is difficult to diagnose due to the lack of mucosal lesions on endoscopy, the low diagnostic yield of biopsy and non-specific findings of barium radiology and computerized tomography. Rectal endoscopic ultrasonography has had a radical impact on the differential diagnosis of stenosing lesions of the rectum, among them linitis plastica, allowing diagnosis of this lesion even in patients with negative results of biopsy.

Linitis plástica de recto primaria / Primary linitis plastica of the rectum

La linitis plástica rectal es una entidad poco frecuente con gran dificultad en su diagnóstico, debido a la falta de lesión mucosa en la endoscopia, la baja rentabilidad de las biopsias y los hallazgos inespecíficos en la radiología baritada y la tomografía computarizada. La ultrasonografía endoscópica rectal ha supuesto una revelación en el diagnóstico diferencial de las lesiones estenosantes de recto, entre ellas la linitis plástica, y ha permitido el diagnóstico de esta entidad incluso en pacientes con biopsias negativas

Linitis plastica of the rectum is an uncommon entity that is difficult to diagnose due to the lack of mucosal lesions on endoscopy, the low diagnostic yield of biopsy and non-specific findings of barium radiology and computerized tomography. Rectal endoscopic ultrasonography has had a radical impact on the differential diagnosis of stenosing lesions of the rectum, among them linitis plastica, allowing diagnosis of this lesion even in patients with negative results of biopsy