Phagoptosis - Cell Death By Phagocytosis - Plays Central Roles in Physiology, Host Defense and Pathology.

Cell death by phagocytosis - termed 'phagoptosis' for short - is a form of cell death caused by the cell being phagocytosed i.e. recognised, engulfed and digested by another cell. Phagocytes eat cells that: i) expose 'eat-me' signals, ii) lose 'don't-eat-me' signals, and/or iii) bind opsonins. Live cells may express such signals as a result of cell stress, damage, activation or senescence, which can result in phagoptosis. Phagoptosis may be the most abundant form of cell death physiologically as it mediates erythrocyte turnover. It also regulates: reproduction by phagocytosis of sperm, development by removal stem cells and excess cells, and immunity by removal of activated neutrophils and T cells. Phagoptosis mediates the recognition of non-self and host defence against pathogens and cancer cells. However, in inflammatory conditions, excessive phagoptosis may kill our cells, leading to conditions such as hemophagy and neuronal loss.

Electroquimioterapia en metástasis cutáneas de melanoma: experiencia en 31 casos / Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases

INTRODUCCIÓN Y OBJETIVOS: la electroquimioterapia (EQT) es una técnica terapéutica indicada en tumores cutáneos y subcutáneos no resecables quirúrgicamente. La EQT se fundamenta en la acción sinérgica de un fármaco antineoplásico junto con la electroporación de las membranas celulares para aumentar su citotoxicidad. El objetivo del presente estudio es objetivar la eficacia clínica, así como el perfil de seguridad de la EQT como tratamiento en pacientes con recidivas o metástasis cutáneas locorregionales de melanoma no abordables quirúrgicamente. MATERIAL Y MÉTODOS: Entre enero de 2007 y diciembre de 2012 se incluyeron 31 pacientes. Todos los tratamientos se realizaron siguiendo las guías de consenso European Standard Operating Procedures of Electrochemotherapy (ESOPE). La respuesta se calculó por paciente, obteniendo la media del conjunto de las lesiones. RESULTADOS: En el 49% de los casos se demostró una respuesta parcial y en el 23% se obtuvo una respuesta completa. Diecisiete pacientes mantuvieron la respuesta al año de seguimiento. En el 28% existió progresión de la enfermedad. Las complicaciones locales inmediatas (dolor, edema, eritema) fueron leves, y se resolvieron en las primeras 48 h en la mayoría de los casos. Ocho pacientes presentaron complicaciones locales posteriores, como ulceración y sobreinfección, secundarias a la necrosis de las lesiones y fueron controladas con tratamientos tópicos. CONCLUSIONES: La EQT presenta un excelente perfil de eficacia, eficiencia y seguridad, siendo de gran utilidad en el control de la enfermedad locorregional avanzada en el melanoma en lesiones no resecables quirúrgicamente

INTRODUCTION AND OBJECTIVES: electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48 hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions

Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases.

INTRODUCTION AND OBJECTIVES: Electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions.

Dermoscopy structures as predictors of sentinel lymph node positivity in cutaneous melanoma.

BACKGROUND: Histological features such as Breslow thickness, ulceration and mitosis are the main criteria to guide sentinel lymph node biopsy (SLNB) in melanoma. Dermoscopy may add complementary information to these criteria. OBJECTIVES: To evaluate the correlation between dermoscopy structures and SLNB positivity. METHODS: Retrospective analysis of 123 consecutive melanomas with Breslow thickness > 0·75 mm, SLNB performed during follow-up and dermoscopic images. RESULTS: Men were more likely to have a positive SLNB. The presence of ulceration and blotch and the absence of a pigmented network in dermoscopy correlated with positive SLNB. Histological ulceration also correlated with positive SLNB. A dermoscopy SCORE predicted SLN status with a sensitivity of 96·3% and a specificity of 30·2%. When sex and Breslow thickness were added (SCOREBRESEX), the sensitivity remained at 96·3% but the specificity increased to 52·1%. This study is limited by the number of patients and was performed in only one institution. CONCLUSIONS: Dermoscopy allowed a more precise prediction of SLN status. If a combined SCOREBRESEX was used to select patients for SLNB, 41·5% of procedures might be avoided.

Drenaje linfático aberrante en un caso de melanoma en zona epigástrica / Aberrant lymphatic drainage from a melanoma located in epigastric area

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Desmoplastic melanoma on the nose: electrochemotherapy as an alternative treatment to local advanced disease.

BACKGROUND: Desmoplastic malignant melanoma (DMM) is a rare and usually misdiagnosed type of melanoma. Delayed detection at complicated anatomical locations can lead to the necessity of alternative therapies. OBJECTIVE: Characterization of DMM on the nose, which is the second more frequent type of MM. METHODS: Review of case series of eight pathologically proven DMM on the nose from two referral centres with a mean follow-up of 69 ± 40.5 months. RESULTS: According to a single centre experience, there is a more than 70-fold increased risk of having a DMM on the nose compared with a non-DMM (P < 0.0005, CI99% 16.3-317.3). Clinical and pathological misdiagnoses were frequent, only three of the eight cases were properly diagnosed and treated and indeed they did not experience relapses. Due to non-clinical suspicion and superficial biopsies, three cases were initially pathologically misdiagnosed as basal cell carcinomas and a nevus respectively. Atypical vessels and remnants of pigment on dermoscopy are indicative findings even in non-pigmented cases. Although not significant, the mean disease-free survival differed between cases with a correct initial management (four cases, 66.7 ± 57.3 months) in contrast to improper (four cases, 16.25 ± 18.9 months). Electrochemotherapy achieved a complete local control of disease in two cases unsuitable for surgery. CONCLUSIONS: Use of dermoscopy and correctly selected biopsy of lesions on the face is mandatory to improve early diagnosis of DMM. Improper management of challenging cases implies a more complicated therapy and loco-regional invasion risk. Electrochemotherapy could be a promising therapy in local advanced tumours.

Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma

INTRODUCTION: The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT. AIM AND METHODS: The purpose of the present retrospective study was to review the results of loco-regional control after postoperative RT in patients with nodal metastases of melanoma. Seventy-seven patients with high-risk disease (lymph nodes > or =3 cm, more than three lymph nodes involved, extracapsular extension and recurrent disease) were treated with adjuvant RT. Hypofractionation was used in 65 patients and conventional fractionation in 12 patients. RESULTS: Seventy-seven patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. The median age was 56 years old (range: 21-83). There were 47 males (61%) and 30 females (39%). Loco-regional control was observed in 95% of patients (73/77). The actuarial 5-year in-field loco-regional control rate was 90% (mean: 105 months; CI95%: 96-115 months). Median metastasis disease- free survival (MDFS) was 16 months (CI95%: 13-18 months). Median survival time (MST) for the entire group was 26 months (CI95%: 18-34 months). MST according to the localisation of node metastases (groin, axilla and cervical) was also analysed, without statistically significant differences (p=0.08). Concerning the number of risk factors score, analysis of survival did not show statistically significant differences (p=0.055). CONCLUSIONS: Despite the high incidence of distant metastases, loco-regional control remains an important goal in the management of melanoma. Surgery and adjuvant RT provides excellent loco-regional control, although distant metastases remain the major cause of mortality (AU)

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Prognostic value of tyrosinase reverse transcriptase PCR analysis in melanoma sentinel lymph nodes: long-term follow-up analysis.

OBJECTIVE: To determine the prognostic value of detecting tyrosinase transcripts in melanoma sentinel lymph nodes (SLNs). METHODS: Reverse transcription (RT) PCR for tyrosinase mRNA was performed on negative SLNs of 76 patients with melanoma. RESULTS: Tyrosinase mRNA was found in 39 patients (51.3%). After a median follow-up period of 51 months, significant differences were found in overall survival (OS) but not in disease-free survival (DFS). The 5-year OS and DFS rates were 97.2% and 80%, respectively, for RT-PCR tyrosinase-negative (TN) patients vs. 78.67% and 66.24% for RT-PCR tyrosinase-positive (TP) patients (P = 0.019 and P = 0.38, respectively). Of four progressing patients in the TN group, three relapsed with subcutaneous, soft-tissue or lymph-node metastases, while seven out of nine progressing patients in the TP group relapsed at visceral sites. CONCLUSIONS: No significant differences in DFS were found by RT-PCR tyrosinase expression analysis at melanoma SLNs. Significant differences in OS could be related to a different pattern of relapse and must be confirmed after a longer follow-up time.

[Detection of episodes of ischemic tissue hypoxia by means of the combined intraoperative neurophysiologic monitoring with the tissue oxygenation monitoring in aneurysm surgery]. / Detección de episodios de hipoxia tisular isquémica mediante la monitorizaciónneurofisiológica intraoperatoria combinada con la monitorización de la oxigenacióntisular en la cirugía aneurismática.

INTRODUCTION: Intraoperative neuromonitoring in aneurysm surgery can be very useful to determine inadequate positions of the vascular clip that cause partial or complete compromise of the cerebral sanguineous flow in the vascular territories irrigated by the arteries related to aneurysm. The direct visualization of these arteries after the application of the surgical clip can be insufficient in detecting this potentially detrimental situation. Knowing this circumstance on the onset would allow the neurosurgeon to correct it and to avoid, therefore, cerebral ischemic tissue hypoxia. We show the utility of the intraoperative monitoring of the oxygen tissue pressure (PtiO2) and the somatosensorial evoked potential (SSEP) for the detection of these situations with the example of a clinical case. CLINICAL CASE: We present the case of a 62 year-old woman, that presented with subarachnoid hemorrhage of aneurysmal origin. The cerebral arteriography demonstrated the existence of an aneurysm of the posterior communicating artery that was treated initially by endovascular procedure with partial exclusion of the aneurysm. For this reason it was decided to complete the treatment with a programmed surgery. The patient was put on an intraoperative monitoring system with a PtiO2 sensor located in the risk area and with SSEP. After positioning the surgical clip the partial oxygen pressure decreased rapidly, as well as the amplitude of the cortical potential of the left posterior tibial nerve. The knowledge of this situation allowed the detection of a trapped posterior communicating artery. After correcting this situation by replacing the surgical clip, both variables recovered to their basal values. CONCLUSIONS: The intraoperative PtiO2 monitoring, combined with neurophysiologic monitoring during aneurysm surgery offers a fast and trustworthy form of early detection of ischemic phenomena caused by bad positioning of the surgical clip.

Detección de episodios de hipoxia tisular isquémica mediante la monitorización neurofisiológica intraoperatoria combinada con la monitorización de la oxigenación tisular en la cirugía aneurismática / Detection of episodes of ischemic tissue hypoxia by means of the combined intraoperative neurophysiologic monitoring with the tissue oxygenation monitoring in aneurysm surgery

Introducción. La neuromonitorización intraoperatoria en la cirugía aneurismática puede ser de gran utilidad para determinar posiciones inadecuadas del clip que ocasionen un compromiso parcial o completo del flujo sanguíneo cerebral en los territorios vasculares irrigados por las arterias relacionadas con el aneurisma. La visualización directa de estas arterias tras la aplicación del clip quirúrgico puede ser insuficiente para detectar esta situación potencialmente deletérea. El conocimiento precoz de esta circunstancia permitiría al neurocirujano corregirla y evitar así la hipoxia tisular cerebral isquémica. Mostramos, con el ejemplo de un caso clínico, la utilidad de la monitorización intraoperatoria de la presión tisular de oxígeno (PtiO2) y de los potenciales evocados somato sensoriales (PESS) para la detección de estas situaciones. Caso clínico. Presentamos el caso de una mujer de 62 años de edad, que debutó con una hemorragia subaracnoidea de origen aneurismático. La arteriografía cerebral demostró la existencia de un aneurisma de la arteria comunicante posterior izquierda que fue tratado inicialmente por vía endovascular con exclusión parcial del aneurisma. Por este motivo se decidió completar el tratamiento mediante cirugía programada. La paciente fue monitorizada intraoperatoriamente con un sensor de PtiO2 situado en el área de riesgo y con PESS. Tras la colocación del clip se produjo una rápida caída de la presión parcial de oxígeno, así como disminución de la amplitud del potencial cortical del nervio tibial posterior izquierdo. El conocimiento de esta situación, permitió detectar un atrapamiento de la arteria comunicante posterior. Tras corregir esta situación reposicionando el clip quirúrgico, ambas variables recuperaron sus valores basales. Conclusiones. La monitorización intraoperatoria dela PtiO2 combinada con la monitorización neurofisiológica durante la cirugía aneurismática ofrece, de una forma rápida y fiable, la detección precoz de fenómenos isquémicos ocasionados por mal posicionamiento del clip quirúrgico

Introduction. Intraoperative neuromonitoring in aneurysm surgery can be very useful to determine inadequate positions of the vascular clip that cause partial or complete compromise of the cerebral sanguineous flow in the vascular territories irrigated by the arteries related to aneurysm. The direct visualization of these arteries after the application of the surgical clip can be insufficient in detecting this potentially detrimental situation. Knowing this circumstance on the onset would allow the neurosurgeon to correct it and to avoid, therefore, cerebral ischemic tissue hypoxia. We show the utility of the intraoperative monitoring of the oxygen tissue pressure (PtiO2) and the somato sensorial evoked potential (SSEP) for the detection of these situations with the example of a clinical case. Clinical case. We present the case of a 62 year-old woman, that presented with subarachnoid hemorrhage of aneurysmal origin. The cerebral arteriography demonstrated the existence of an aneurysm of the posterior communicating artery that was treated initially by endovascular procedure with partial exclusion of the aneurysm. For this reason it was decided to complete the treatment with a programmed surgery. The patient was put on an intraoperative monitoring system with a PtiO2 sensor located in the risk area and with SSEP. After positioning the surgical clip the partial oxygen pressure decreased rapidly, as well as the amplitude of the cortical potential of the left posterior tibial nerve. The knowledge of this situation allowed the detection of a trapped posterior communicating artery. After correcting this situation by replacing the surgical clip, both variables recovered to their basal values. Conclusions. The intraoperative PtiO2 monitoring, combined with neurophysiologic monitoring during aneurysm surgery offers a fast and trustworthy form ofearly detection of ischemic phenomena caused by bad positioning of the surgical clip

Brain contusions induce a strong local overexpression of MMP-9. Results of a pilot study.

BACKGROUND: Brain contusions are inflammatory evolutive lesions that induce intracranial pressure increase and edema, contributing to neurological outcome. Matrix metalloproteinases (MMPs) 2 and 9 can degrade the majority of the extracellular matrix components, and are implicated in blood-brain barrier disruption and edema formation. The aim of this study was to investigate MMP-2 and MMP-9 profiles in human brain contusions using zymography. METHODS: A prospective study was conducted in 20 traumatic brain injury patients where contusion brain tissue was resected. Brain tissues from lobectomies were used as controls. Brain homogenates were analysed by gelatin zymography and in situ zimography was performed to confirm results, on one control and one brain contusion tissue sample. FINDINGS: MMP-2 and MMP-9 levels were higher in brain contusions when compared to controls. MMP-9 was high during the first 24 hours and at 48 to 96 hours, whereas MMP-2 was slightly high at 24 to 96 hours. In situ zymography confirmed gelatin zymography results. A relation between outcome and MMP-9 levels was found; MMP-9 levels were higher in patients with worst outcome. CONCLUSIONS: Our results indicate strong time-dependent gelatinase expression primarily from MMP-9, suggesting that the inflammatory response induced by focal lesions should be considered as a new therapeutic target.

Aumento de los niveles plasmáticos de metaloproteasas de matriz en la fase aguda del traumatismo craneoencefálico / Increased plasma levels of matrix metalloproteases in the early phase after traumatic brain injury

Las metaloproteasas de matriz (MMPs) son enzimas proteolíticos que remodelan y mantienen la matriz extracelular, pero que participan en distintos tipos de lesión cerebral. El objetivo del estudio fue determinar el patrón temporal de los niveles de MMP-2 y MMP-9 plasmáticos en pacientes que presentaron un traumatismo craneoencefálico (TCE). Se incluyeron 20 pacientes con un TCE grave o moderado y se utilizaron tres grupos control (TCE leves con TC normal, pacientes politraumáticos sin TCE y voluntarios sanos). Losniveles de MMP-2 y MMP-9 en plasma se determinaronmediante la técnica de zimografía. Se observó un incremento significativo de los niveles plasmáticos basales de MMP-2 y MMP-9 comparados con los controles sanos (P<0,001 y P=0,001 respectivamente), seguidos de una disminución significativa de ambas proteasas a las 24 horas post-TCE (P<0,001 y P=0,018 respectivamente). Los resultados sugieren una implicación de dichas MMPs en la respuesta inflamatoria desencadenada tras el TCE

Matrix metalloproteases (MMPs) are a family of zinc-binding proteolytic enzymes that remodel and maintain the extracellular matrix but can act pathologically in various types of brain injury. The purpose of this study was to determine the temporal profile of matrix metalloprotease levels (MMP-2 and MMP-9) in patients with traumatic brain injury (TBI). Twenty patients with a moderate or severe TBI were included. Three groups (healthy people, polytraumatic patients without TBI and mild TBI patients with normal CT scan) were used as controls. A zymography technique was used to determinelevels of MMP-2 and MMP-9 in plasma. A significantincrease in plasmatic MMP-9 and MMP-2 levels wasobserved at baseline determination when compared withhealthy volunteers (P<0.001 and P=0.001 respectively),followed by a significant decrease at 24 hours post-TBI(P<0.001 and P=0.018 respectively). The results suggestan implication of MMP-9 and MMP-2 in early systemic andnon-systemic inflammatory response following TBIUnivers

Lymphatic mapping and sentinel node biopsy in Merkel's cell carcinoma.

AIM: The purpose of this study was to determine the predictive value of lymphatic mapping with selective lymphadenectomy in patients with Merkel's cell carcinoma. METHODS: Eight patients with biopsy proven Merkel's cell carcinoma underwent sentinel node biopsy. Lymphoscintigraphy was performed the day before surgery following intradermal injection of 74-111MBq of 99mTc-nanocolloid divided into four doses around the biopsy scar. Dynamic and static images were obtained. RESULTS: At least one sentinel node was visualized in all patients. The sentinel node was intra-operatively identified with the aid of a hand-held gamma probe in all cases and patent blue dye in six out of eight cases. During surgery, all sentinel nodes were successfully harvested. Metastatic cell deposits were subsequently identified in three patients (37.5%) and they underwent regional lymphadenectomy. No additional involved lymph nodes were identified. No recurrence has been reported in a median follow-up of 4.6 years (range: 8 months-10 years). CONCLUSIONS: In conclusion, sentinel node biopsy in patients with Merkel's cell carcinoma appears to be a reliable staging technique.

[Recent advances in regional cerebral monitoring in the neurocritical patient: brain tissue oxygen pressure monitoring, cerebral microdialysis and near-infrared spectroscopy]. / Actualizaciones en los métados de monitorización cerebral regional en los pacientes neurocríticos: presión tisular de oxígeno, microdiálisis cerebral y técnicas de espectroscopía por infrarrojos.

The long term outcome of head-injured patients depends not only on the primary brain lesions but also to a large extent on the secondary lesions. The diagnosis of many secondary lesions, and specially that of brain ischemia, is based on simultaneous monitoring of several intracranial and systemic variables. Continuous intracranial pressure (ICP) monitoring is currently considered indispensable in the management of all patients with a severe head injury and intracranial lesions. However, the information provided by this technique is insufficient to diagnose some of the complex physiopathological processes that characterize traumatic brain lesions. Consequently, the use of methods to estimate cerebral blood flow such as transcranial Doppler and jugular oximetry to complement ICP monitoring is becoming increasingly widespread. Nevertheless, determining the effect of tissue lesions and therapeutic measures on cerebral metabolism currently requires direct access to the brain parenchyma at the bedside. In this review we focus on three methods of regional cerebral monitoring: oxygen tissue pressure (PtiO(2)) monitoring, microdialysis and near-infrared spectroscopy. The bases of each method and reference values for the variables analyzed will be discussed. We also make a series of recommendations on how results should be interpreted in light of current knowledge.

[Global systems for monitoring cerebral hemodynamics in the neurocritical patient: basic concepts, controversies and recent advances in measuring jugular bulb oxygenation]. / Métodos globales de monitorización de la hemodinámica cerebral en el paciente neuricrítico: fundamentos, controversias y actualizaciones en las técnicas de oximetría yugular

Because of the importance of hypoxic/ischemic phenomena in head-injured patients, brain monitoring in these patients should be complemented by systems providing information on cerebral blood flow and metabolism. Indirect estimations of cerebral blood flow have been obtained from blood extracted from the jugular bulb, as a special bedside application of the Fick's principle to the brain. In the last few years, the use of jugular oximetry techniques has become routine in centers treating head-injured and other neurocritical patients such as those presenting subarachnoid hemorrhage or malignant middle cerebral artery infarction. The experience acquired in the use of these techniques, as well as the introduction of new neuromonitoring systems, have deepened our understanding of the information gained and have enabled more precise definition of their indications and limitations. This review describes the basic concepts underlying the use of jugular oximetry techniques in the neurocritical patient. We also explain the reasons why several variables derived from jugular blood such as arterio-jugular differences of lactate (AVDL) or the lactate-oxygen index (LOI) do not provide accurate information on brain metabolism.

Métodos globales de monitorización de la hemodinámica cerebral en el paciente neurocrítico: fundamentos, controversias y actualizaciones en las técnicas de oximetría yugular / Global systems for monitoring cerebral hemodynamics in the neurocritical patient: basic concepts, controversies and recent advances in measuring jugular bulb oxygenation

El papel relevante que la hipoxia tisular cerebral juega en la fisiopatología de los pacientes con un traumatismo craneoencefálico (TCE) justifica la necesidad de complementar la monitorización de estos pacientes con sistemas que aporten información sobre el flujo sanguíneo y el metabolismo cerebral. En la búsqueda de sistemas útiles en la cabecera del paciente, se han utilizado extrapolaciones del principio de Fick al encéfalo, utilizando métodos que estiman el flujo sanguíneo cerebral (FSC) a partir de la obtención de muestras de sangre del bulbo de la yugular. En los últimos años, las técnicas de oximetría yugular se han convertido en elementos de uso frecuente en las unidades que tratan pacientes con un TCE u otros pacientes neurocríticos, como los pacientes con una hemorragia subaracnoidea o con infartos masivos de la arteria cerebral media. El uso frecuente de estas técnicas en las últimas dos décadas, junto a la incorporación de otros sistemas de neuromonitorización, permiten en la actualidad matizar la información que estos métodos globales proporcionan y definir mejor tanto sus indicaciones como sus limitaciones. El objetivo de esta revisión es presentar los fundamentos y los conceptos básicos relacionados con la utilización clínica de las técnicas de oximetría yugular en el paciente neurocrítico. También presentamos y discutimos la evidencia más reciente que indica que determinadas variables, obtenidas de muestras de sangre del bulbo de la yugular, tales como las diferencias arterio-yugulares de lactatos (AVDL) y el índice lactato-oxígeno (LOI), a pesar de su amplia utilización en la práctica clínica diaria, no ofrecen una información fiable sobre el metabolismo cerebral que permita la toma de decisiones terapéuticas

Because of the importance of hypoxic/ischemic phenomena in head-injured patients, brain monitoring in these patients should be complemented by systems providing information on cerebral blood flow and metabolism.Indirect estimations of cerebral blood flow have been obtained from blood extracted from the jugular bulb, as a special bedside application of the Fick’s principle to the brain. In the last few years, the use of jugular oximetry techniques has become routine in centers treating head-injured and other neurocritical patients such as those presenting subarachnoid hemorrhage or malignant middle cerebral artery infarction. The experience acquired in the use of these techniques, as well as the introduction of new neuromonitoring systems, have deepened our understanding of the information gained and have enabled more precise definition of their indications and limitations. This review describes the basic concepts underlying the use of jugular oximetry techniques in the neurocritical patient. We also explain the reasons why several variables derived from jugular blood such as arterio-jugular differences of lactate (AVDL) or the lactate-oxygen index (LOI) do not provide accurate information on brain metabolism

Actualizaciones en los métodos de monitorización cerebral regional en los pacientes neurocríticos: presión tisular de oxígeno, microdiálisis cerebral y técnicas de espectroscopía por infrarrojos / Recent advances in regional cerebral monitoring in the neurocritical patient: brain tissue oxygen pressure monitoring, cerebral microdialysis and near-infrared spectroscopy

El resultado final de los pacientes que han presentado un traumatismo craneoencefálico (TCE) depende de las lesiones primarias, pero también, y en gran medida, de las lesiones secundarias. El diagnóstico de un gran número de lesiones secundarias, y en especial de la isquemia cerebral, se centra en la monitorización simultánea de diversas variables encefálicas y sistémicas. En el momento actual, la monitorización continua de la presión intracraneal (PIC) se considera una medida indispensable en el manejo de los pacientes con un TCE grave que presentan cualquier tipo de lesión intracraneal. Sin embargo, la información que ofrece esta variable es insuficiente para diagnosticar los complejos procesos fisiopatológicos que caracterizan a las lesiones neurotraumáticas. Por ello, cada vez es más frecuente complementar la neuromonitorización de los pacientes con un TCE con métodos de estimación del flujo sanguíneo cerebral (FSC) como el Doppler transcraneal o las técnicas de oximetría yugular. Sin embargo, en el momento actual y en la cabecera del paciente, el conocimiento de la repercusión de las lesiones tisulares y de las medidas terapéuticas sobre el metabolismo cerebral requiere un acceso directo al parénquima encefálico. En esta revisión nos centraremos en tres métodos de monitorización cerebral “regional”: la presión tisular de oxígeno, la microdiálisis cerebral y las técnicas transcutáneas de espectroscopía por infrarrojos. En cada caso se expondrán los fundamentos del método en cuestión, los valores de referencia de los parámetros monitorizados y una serie de recomendaciones sobre cómo pueden interpretarse sus resultados a la luz de los conocimientos actuales

The long term outcome of head-injured patients depends not only on the primary brain lesions but also to a large extent on the secondary lesions. The diagnosis of many secondary lesions, and specially that of brain ischemia, is based on simultaneous monitoring of several intracranial and systemic variables. Continuous intracranial pressure (ICP) monitoring is currently considered indispensable in the management of all patients with a severe head injury and intracranial lesions. However, the information provided by this technique is insufficient to diagnose some of the complex physiopathological processes that characterize traumatic brain lesions. Consequently, the use of methods to estimate cerebral blood flow such as transcranial Doppler and jugular oximetry to complement ICP monitoring is becoming increasingly widespread. Nevertheless, determining the effect of tissue lesions and therapeutic measures on cerebral metabolism currently requires direct access to the brain parenchyma at the bedside. In this review we focus on three methods of regional cerebral monitoring: oxygen tissue pressure (PtiO2) monitoring, microdialysis and near-infrared spectroscopy. The bases of each method and reference values for the bless analyzed will be discussed. We also make a series of recommendations on how results should be interpreted in light of current knowledge

Angiolymphoid hyperplasia with eosinophilia of the nail bed and bone: successful treatment with radiation therapy.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare entity characterized by the presence of one or several papules or nodules in the skin. Histopathology of ALHE shows a marked proliferation of blood vessels with distinctive large endothelial cells and variable inflammatory infiltrates with eosinophils. We report a 32-year-old Caucasian woman with multiple nodules involving the skin, subcutaneous tissue and bone of the distal phalanx of the fingers that were treated successfully with orthovoltage radiation therapy (40 Gy/20 fractions) and without any side-effects after 9 years of follow-up.

Moderate hypothermia in the management of severe traumatic brain injury: a good idea proved ineffective?

Many drugs with proven efficacy in the preclinical stage have failed to show any benefit in improving the outcome of severe traumatic brain injury (TBI) when tested in controlled clinical trials. Hypothermia is still the most powerful neuroprotective method in experimental models of TBI. Its ability to influence the multiple biochemical cascades that are set in motion after TBI is quite unique. In experimental models hypothermia protects against mechanical neuronal and axonal injury and improves behavioral outcome. Encouraging results from phase II and III clinical trials of hypothermia in TBI reported in the 1990s generated great enthusiasm. However, enthusiasm faded in 2001 after the final report of the multicenter phase III trial in which the neuroprotective effects of moderate hypothermia in TBI were formally tested. This study found no significant effect on outcome in the hypothermia group, leading many clinicians to lose interest in this therapy. The present article reviews the historical background of the use of hypothermia, presents the rationale for using both immediate and deferred hypothermia, and summarizes both experimental and clinical evidence supporting its potential benefits in the management of severe TBI. New technologies using intravascular methods to induce fast hypothermia have recently become available. Cooling either through the intravenous or intra-arterial route is an exciting alternative with great potential. We argue that moderate hypothermia is still the most powerful neuroprotective candidate for severe TBI and that it merits further research and discussion. We also defend the need for further clinical trials to prove or refute its potential for treating high intracranial pressure refractory to first level therapeutic measures. The premature abandonment of hypothermia could close new avenues for improving the devastating effects of TBI.