A method to predict space radiation biological effectiveness for non-cancer effects following intense Solar Particle Events.

In addition to the continuous exposure to cosmic rays, astronauts in space are occasionally exposed to Solar Particle Events (SPE), which involve less energetic particles but can deliver much higher doses. The latter can exceed several Gy in a few hours for the most intense SPEs, for which non-stochastic effects are thus a major concern. To identify adequate shielding conditions that would allow respecting the dose limits established by the various space agencies, the absorbed dose in the considered organ/tissue must be multiplied by the corresponding Relative Biological Effectiveness (RBE), which is a complex quantity depending on several factors including particle type and energy, considered biological effect, level of effect (and thus absorbed dose), etc. While in several studies only the particle-type dependence of RBE is taken into account, in this work we developed and applied a new approach where, thanks to an interface between the FLUKA Monte Carlo transport code and the BIANCA biophysical model, the RBE dependence on particle energy and absorbed dose was also considered. Furthermore, we included in the considered SPE spectra primary particles heavier than protons, which in many studies are neglected. This approach was then applied to the October 2003 SPE (the most intense SPE of solar cycle 23, also known as "Halloween event") and the January 2005 event, which was characterized by a lower fluence but a harder spectrum, i.e., with higher-energy particles. The calculation outcomes were then discussed and compared with the current dose limits established for skin and blood forming organs in case of 30-days missions. This work showed that the BIANCA model, if interfaced to a radiation transport code, can be used to calculate the RBE values associated to Solar Particle Events. More generally, this work emphasizes the importance of taking into account the RBE dependence on particle energy and dose when calculating equivalent doses.

Application to nonlinear optical properties of the RSX-QIDH double-hybrid range-separated functional.

The effective calculation of static nonlinear optical properties requires a considerably high accuracy at a reasonable computational cost, to tackle challenging organic and inorganic systems acting as precursors and/or active layers of materials in (nano-)devices. That trade-off implies to obtain very accurate electronic energies in the presence of externally applied electric fields to consequently obtain static polarizabilities ( α i j ) and hyper-polarizabilities ( ß i j k and γ i j k l ). Density functional theory is known to provide an excellent compromise between accuracy and computational cost, which is however largely impeded for these properties without introducing range-separation techniques. We thus explore here the ability of a modern (double-hybrid and range-separated) Range-Separated eXchange Quadratic Integrand Double-Hybrid exchange-correlation functional to compete in accuracy with more costly and/or tuned methods, thanks to its robust and parameter-free nature.

Deterioro cognitivo tardío en pacientes con estenosis aórtica tratados con sustitución valvular quirúrgica y con implantación transcatéter de válvula aórtica: estudio comparativo / Delayed cognitive impairment in patients with aortic stenosis treated with surgical valve replacement and transcatheter aortic valve implantation: a comparative study

Introducción El deterioro cognitivo secundario a eventos cerebrovasculares es una complicación frecuente en las intervenciones de reemplazo de válvula aórtica. Nuestro objetivo es el estudio del perfil de deterioro de los pacientes sometidos a reemplazo valvular quirúrgico o implantación de prótesis transcatéter (TAVI) y si éste resulta diferente según la intervención a la que son sometidos y los factores de riesgo basales. Pacientes y métodos Estudio observacional prospectivo, con dos grupos no equivalentes de pacientes (grupo TAVI y grupo quirúrgico). Se realizaron comparaciones intergrupo en varios dominios cognitivos, con una evaluación basal y mediciones de seguimiento seis y 12 meses después la intervención. Resultados El grupo TAVI presentó resultados inferiores al grupo quirúrgico en funciones ejecutivas y visuoespaciales, puntuaciones parcialmente determinadas por la edad (p < 0,01) y el nivel intelectual previo (Pearson cociente intelectual previo-medias escalares en los test: 0,665; p < 0,001). La media de puntuaciones en los tres momentos de medición indica una disminución del rendimiento en funciones ejecutivas a los seis meses, que se recupera a los 12 meses. En memoria se registraron incrementos sostenidos en ambos momentos, en tanto que la función visuoespacial y la denominación no mostraron recuperación posterior de los niveles basales. Estas tendencias son similares en los dos grupos. Conclusión Los resultados obtenidos no confirman la instauración de un proceso específico de deterioro neurocognitivo postintervención en la estenosis aórtica complicada. El perfil de deterioro no presenta diferencias significativas entre los grupos, pero es más evidente en los pacientes con TAVI, debido a la influencia de las variables de selección de la muestra. (AU)

INTRODUCTION Cognitive impairment secondary to cerebrovascular events is a common complication of aortic valve replacement interventions. Our aim is to study the deterioration profile of patients who have undergone surgical valve replacement or transcatheter valve implantation (TAVI) and whether it differs according to the intervention they underwent and their baseline risk factors. PATIENTS AND METHODS We conducted a prospective observational study with two non-equivalent groups of patients (TAVI group and surgical group) Intergroup comparisons were carried out in several cognitive domains, with a baseline assessment and follow-up measurements six and 12 months after the intervention. RESULTS The TAVI group performed less well than the surgical group in executive and visuospatial functions, with scores partially determined by age (p < 0.01) and prior intellectual level (Pearson prior intelligence quotient-scalar test means: 0.665; p < 0.001). Mean scores at the three measurement points indicate a decline in executive function performance at six months, which is restored at 12 months. Sustained increases in memory were recorded at both time points, while visuospatial function and naming showed no subsequent recovery of the baseline levels. These trends are similar in both groups. CONCLUSION. The results obtained do not confirm the appearance of a specific process of post-intervention neurocognitive impairment in complicated aortic stenosis. The deterioration profile does not show any significant differences between groups, but is more evident in TAVI patients, due to the influence of variables related to sample selection. (AU)

[Delayed cognitive impairment in patients with aortic stenosis treated with surgical valve replacement and transcatheter aortic valve implantation: a comparative study]. / Deterioro cognitivo tardío en pacientes con estenosis aórtica tratados con sustitución valvular quirúrgica y con implantación transcatéter de válvula aórtica: estudio comparativo.

INTRODUCTION: Cognitive impairment secondary to cerebrovascular events is a common complication of aortic valve replacement interventions. Our aim is to study the deterioration profile of patients who have undergone surgical valve replacement or transcatheter valve implantation (TAVI) and whether it differs according to the intervention they underwent and their baseline risk factors. PATIENTS AND METHODS: We conducted a prospective observational study with two non-equivalent groups of patients (TAVI group and surgical group) Intergroup comparisons were carried out in several cognitive domains, with a baseline assessment and follow-up measurements six and 12 months after the intervention. RESULTS: The TAVI group performed less well than the surgical group in executive and visuospatial functions, with scores partially determined by age (p < 0.01) and prior intellectual level (Pearson prior intelligence quotient-scalar test means: 0.665; p < 0.001). Mean scores at the three measurement points indicate a decline in executive function performance at six months, which is restored at 12 months. Sustained increases in memory were recorded at both time points, while visuospatial function and naming showed no subsequent recovery of the baseline levels. These trends are similar in both groups. CONCLUSION: The results obtained do not confirm the appearance of a specific process of post-intervention neurocognitive impairment in complicated aortic stenosis. The deterioration profile does not show any significant differences between groups, but is more evident in TAVI patients, due to the influence of variables related to sample selection.

TITLE: Deterioro cognitivo tardío en pacientes con estenosis aórtica tratados con sustitución valvular quirúrgica y con implantación transcatéter de válvula aórtica: estudio comparativo.Introducción. El deterioro cognitivo secundario a eventos cerebrovasculares es una complicación frecuente en las intervenciones de reemplazo de válvula aórtica. Nuestro objetivo es el estudio del perfil de deterioro de los pacientes sometidos a reemplazo valvular quirúrgico o implantación de prótesis transcatéter (TAVI) y si éste resulta diferente según la intervención a la que son sometidos y los factores de riesgo basales. Pacientes y métodos. Estudio observacional prospectivo, con dos grupos no equivalentes de pacientes (grupo TAVI y grupo quirúrgico). Se realizaron comparaciones intergrupo en varios dominios cognitivos, con una evaluación basal y mediciones de seguimiento seis y 12 meses después la intervención. Resultados. El grupo TAVI presentó resultados inferiores al grupo quirúrgico en funciones ejecutivas y visuoespaciales, puntuaciones parcialmente determinadas por la edad (p < 0,01) y el nivel intelectual previo (Pearson cociente intelectual previo-medias escalares en los test: 0,665; p < 0,001). La media de puntuaciones en los tres momentos de medición indica una disminución del rendimiento en funciones ejecutivas a los seis meses, que se recupera a los 12 meses. En memoria se registraron incrementos sostenidos en ambos momentos, en tanto que la función visuoespacial y la denominación no mostraron recuperación posterior de los niveles basales. Estas tendencias son similares en los dos grupos. Conclusión. Los resultados obtenidos no confirman la instauración de un proceso específico de deterioro neurocognitivo postintervención en la estenosis aórtica complicada. El perfil de deterioro no presenta diferencias significativas entre los grupos, pero es más evidente en los pacientes con TAVI, debido a la influencia de las variables de selección de la muestra.

Gastric adenocarcinoma: A review of the TNM classification system and ways of spreading.

Gastric cancer is the fifth most common cancer in the world. The most common histologic subtype is adenocarcinoma. Gastric adenocarcinomas are staged using the American Joint Committee on Cancer's 8th TNM classification. The perigastric ligaments, mesentery, omentum, and potential spaces between the parietal and visceral peritoneal linings play are important structures for staging. The spread of disease is influenced by the location of the tumor within the stomach, as well as by the anatomy related to the ligaments and lymph vessels. CT is the imaging modality of choice for the preoperative clinical staging of gastric cancer, and it is essential for planning treatment. To be able to do an adequate imaging workup, radiologists need to know the different pathways through which gastric cancer can spread: lymphatic, subperitoneal, direct invasion, transperitoneal, hematogenous, and extramural venous invasion.

Adenocarcinoma gástrico: revisión del TNM y de las vías de diseminación / Gastric adenocarcinoma: A review of the TNM classification system and ways of spreading

El cáncer gástrico es el quinto cáncer más frecuente en el mundo. El subtipo histológico más frecuente es el adenocarcinoma. Para su estadificación se utiliza la 8.ª edición de la clasificación TNM de la American Joint Comittee on Cancer. Los ligamentos perigástricos, el mesenterio, el omento y los espacios potenciales entre los revestimientos peritoneales parietal y visceral, son estructuras con gran implicación en la estadificación. La diseminación de la enfermedad se ve afectada por la localización del tumor en el estómago, así como por la anatomía ligamentaria y linfática. La tomografía computarizada es la modalidad de imagen de elección para la estadificación clínica preoperatoria del cáncer gástrico, y es esencial para la planificación del tratamiento. Existen múltiples vías de diseminación en el cáncer gástrico que se deben conocer para poder realizar una correcta valoración radiológica: linfática, subperitoneal, invasión directa, transperitoneal, hematógena e invasión venosa extramural. (AU)

Gastric cancer is the fifth most common cancer in the world. The most common histologic subtype is adenocarcinoma. Gastric adenocarcinomas are staged using the American Joint Committee on Cancer's 8th TNM classification. The perigastric ligaments, mesentery, omentum, and potential spaces between the parietal and visceral peritoneal linings are important structures for staging. The spread of disease is influenced by the location of the tumor within the stomach, as well as by the anatomy related to the ligaments and lymph vessels. CT is the imaging modality of choice for the preoperative clinical staging of gastric cancer, and it is essential for planning treatment. To be able to do an adequate imaging workup, radiologists need to know the different pathways through which gastric cancer can spread: lymphatic, subperitoneal, direct invasion, transperitoneal, hematogenous, and extramural venous invasion. (AU)

Hepatocyte-like cells differentiated from methylmalonic aciduria cblB type induced pluripotent stem cells: A platform for the evaluation of pharmacochaperoning.

Methylmalonic aciduria cblB type (MMA cblB type, MMAB OMIM #251110), caused by a deficiency in the enzyme ATP:cob(I)alamin adenosyltransferase (ATR, E.C_2. 5.1.17), is a severe metabolic disorder with a poor prognosis despite treatment. We recently described the potential therapeutic use of pharmacological chaperones (PCs) after increasing the residual activity of ATR in patient-derived fibroblasts. The present work reports the successful generation of hepatocyte-like cells (HLCs) differentiated from two healthy and two MMAB induced pluripotent stem cell (iPSC) lines, and the use of this platform for testing the effects of PCs. The MMAB cells produced little ATR, showed reduced residual ATR activity, and had higher concentrations of methylmalonic acid compared to healthy HLCs. Differential proteome analysis revealed the two MMAB HCLs to show reproducible differentiation, but this was not so for the healthy HLCs. Interestingly, PC treatment in combination with vitamin B12 increased the amount of ATR available, and subsequently ATR activity, in both MMAB HLCs. More importantly, the treatment significantly reduced the methylmalonic acid content of both. In summary, the HLC model would appear to be an excellent candidate for the pharmacological testing of the described PCs, for analyzing the effects of new drugs, and investigating the repurposing of older drugs, before testing in animal models.

An updated review of the TNM classification system for cancer of the oesophagus and its complications.

Cancer of the esophagus is an aggressive cancer with high mortality. Because of the esophagus's lack of serosa and its peculiar lymphatic drainage, esophageal cancer is diagnosed in advanced stages. The eighth edition of the TNM (2017) aims to standardize care for esophageal cancer throughout the world; it includes not only patients treated with esophagectomy alone, but also those receiving neoadjuvant chemotherapy and/or radiotherapy. One new development in the eighth edition is that it establishes separate classifications for different time periods, with pathologic stage groups for prior to treatment (cTNM), after esophagectomy (pTNM), and after neoadjuvant therapy (ypTNM). The combined use of endoscopic ultrasound, CT, PET-CT, and MRI provides the greatest accuracy in determining the clinical stage, and these techniques are essential for planning treatment and for evaluating the response to neoadjuvant treatment. Esophagectomy continues to be the main treatment; it is also the elective gastrointestinal surgery that has the highest mortality, and it carries the risk of multiple complications, including anastomotic leaks, pulmonary complications, technical complications, and functional complications.

Biological effectiveness of He-3 and He-4 ion beams for cancer hadrontherapy: a study based on the BIANCA biophysical model.

While cancer therapy with protons and C-ions is continuously spreading, in the near future patients will be also treated with He-ions which, in comparison to photons, combine the higher precision of protons with the higher relative biological effectiveness (RBE) of C-ions. Similarly to C-ions, also for He-ions the RBE variation along the beam must be known as precisely as possible, especially for active beam delivery systems. In this framework the BIANCA biophysical model, which has already been applied to calculate the RBE along proton and C-ion beams, was extended to4He-ions and, following interface with the FLUKA code, was benchmarked against cell survival data on CHO normal cells and Renca tumour cells irradiated at different positions along therapeutic-like4He-ion beams at the Heidelberg Ion-beam Therapy centre, where the first He-ion patient will be treated soon. Very good agreement between simulations and data was obtained, showing that BIANCA can now be used to predict RBE following irradiation with all ion types that are currently used, or will be used soon, for hadrontherapy. Thanks to the development of a reference simulation database describing V79 cell survival for ion and photon irradiation, these predictions can be cell-type specific because analogous databases can be produced, in principle, for any cell line. Furthermore, survival data on CHO cells irradiated by a He-3 beam were reproduced to compare the biophysical properties of He-4 and He-3 beams, which is currently an open question. This comparison showed that, at the same depth, He-4 beams tend to have a higher RBE with respect to He-3 beams, and that this difference is also modulated by the considered physical dose, as well as the cell radiosensitivity. However, at least for the considered cases, no significant difference was found for the ratio between the RBE-weighted dose in the SOBP and that in the entrance plateau.

Does a single application of contraceptive cause pathological changes in bitches? / [Uma única aplicação de anticoncepcional causa alterações patológicas em cadelas?]

O presente trabalho objetivou avaliar os efeitos da administração em dose única de progestágenos em fêmeas caninas hígidas, as quais nunca haviam recebido tais fármacos. Foram selecionadas 20 cadelas, que foram examinadas clinicamente e por meio de exames complementares. Nessas cadelas, foi aplicado medroxiprogesterona por via subcutânea. Noventa dias após, as fêmeas foram esterilizadas cirurgicamente, sendo os tecidos reprodutivos encaminhados para histopatologia. Foi possível verificar que, aos 30 dias, 12 animais (60%) apresentaram hiperplasia mamária. Aos 90 dias, 18 animais (90%) apresentavam sinais de hiperplasia endometrial cística, tendo cinco (27,77%) destes animais apresentado conteúdo purulento no lúmen uterino. No exame microscópico, apenas uma fêmea não demonstrou alterações patológicas, sendo a única que recebeu o contraceptivo na fase correta (anestro). As demais fêmeas apresentaram alterações que variaram entre alterações circulatórias a hiperplasia endometrial cística grave. Assim, foi possível concluir que uma única aplicação de anticoncepcional em fêmeas hígidas pode causar complicações leves a graves.(AU)

Efectos adversos de las terapias dirigidas contra el cáncer: lo que el radiólogo debe saber / Adverse events of targeted anticancer therapies: what radiologists need to know

El tratamiento del cáncer ha avanzado drásticamente en las últimas décadas. Un mayor conocimiento de la biología tumoral ha propiciado el desarrollo de nuevos fármacos anticancerígenos, llamados "terapias dirigidas". Estos fármacos tienen como diana vías de señalización específicas necesarias para el desarrollo del cáncer. Más novedosa es aún la inmunoterapia. Estos nuevos agentes se pueden clasificar en diferentes grupos, principalmente según su mecanismo de acción: inhibidores de VEGF o antiangiogénicos, inhibidores de EGFR, inhibidores de mTOR, inhibidores de CTLA-4, inhibidores de PD-1/PD-L1, etc. Todas estas nuevas terapias traen consigo nuevos efectos adversos que el radiólogo debe conocer. Entender el mecanismo molecular de las terapias dirigidas y reconocer sus efectos adversos es esencial para una correcta valoración radiológica y para proporcionar un tratamiento apropiado

The treatment of cancer has improved drastically in recent decades. Better understanding of tumor biology has enabled the development of new treatments, called targeted therapy. These drugs target specific signaling pathways that are necessary for the development of cancer. Immunotherapy is even more novel. These new agents can be classified into different groups, mainly according to their mechanism of action: VEGF inhibitors or anti-angiogenic agents, EGFR inhibitors, mTOR inhibitors, CTLA-4 inhibitors, or PD-1/PD-L1 inhibitors, etc. All these new treatments are accompanied by new adverse effects that radiologists need to know. Understanding the molecular mechanisms of targeted therapies and knowing their adverse effects are vital to imaging assessment and ensuring appropriate treatment

[Neuropsychological profile in patients with myotonic dystrophy type 1: a four-year follow-up study]. / Perfil neuropsicológico en pacientes con distrofia miotónica tipo 1: estudio de seguimiento a cuatro años.

INTRODUCTION: Myotonic dystrophy type 1 (MD1), or Steinert's disease, is a multisystemic disorder of autosomal dominant inheritance, whose adult variant usually presents with multidomain cognitive impairment and affects patients' functionality and quality of life. AIM: To study the four-year history of cognitive functioning in a sample of patients with the adult variant of MD1. PATIENTS AND METHODS: The neurocognitive functions of a sample of 31 patients with MD1 are evaluated, of whom 24 repeat the test administered four years ago in the Neurology Service of the Complejo Hospitalario of Navarra. Data are collected from the cognitive domains that are most related to the deficits that usually present in MD1. RESULTS: The follow-up evaluation found that the visuospatial and visuoconstructive functions and alternating attention of the patients who underwent the study were affected, as was their daily functioning reported by the family. These results are in line with those obtained four years earlier, with no significant deterioration observed between the two measurements. A higher incidence of cognitive impairment was also displayed in 2018, with some cases of progression to dementia in Steinert's disease. CONCLUSION: Neurocognitive progression in MD1 seems to respond to a progressive pattern of degeneration, linked to the functions that are most affected from the beginning of the sequelae phase and which usually correspond to the domains of working memory, alternating attention, and visuospatial and visuoconstructive abilities.

TITLE: Perfil neuropsicológico en pacientes con distrofia miotónica tipo 1: estudio de seguimiento a cuatro años.Introducción. La distrofia miotónica tipo 1 (DM1), o enfermedad de Steinert, es un trastorno multisistémico de herencia autosómica dominante, cuya variante adulta suele cursar con deterioro cognitivo multidominio y afectación de la funcionalidad y la calidad de vida de los pacientes. Objetivo. Estudiar la evolución a cuatro años del funcionamiento cognitivo de una muestra de pacientes con la variante adulta de DM1. Pacientes y métodos. Se evalúan las funciones cognitivas de una muestra de 31 pacientes con DM1, de los cuales 24 repiten la evaluación administrada hace cuatro años en el Servicio de Neurología del Complejo Hospitalario de Navarra. Se recogen datos de los dominios neurocognitivos más relacionados con los déficits de presentación habitual en la DM1. Resultados. La evaluación de seguimiento constató la afectación de las funciones visuoespaciales y visuoconstructivas y de la atención alternante de los pacientes que se sometieron al estudio, así como de su funcionamiento cotidiano informado por la familia. Estos resultados están en línea con los obtenidos cuatro años atrás, sin que se haya objetivado un deterioro significativo entre ambas mediciones. Se demuestra, además, una mayor incidencia de deterioro cognitivo en 2018, con algunos casos de evolución a demencia en la enfermedad de Steinert. Conclusión. La evolución neuropsicológica en la DM1 parece responder a un patrón progresivo, ligado a las funciones que más se afectan desde los inicios de la fase de secuelas y que suelen corresponder a los dominios de memoria de trabajo, atención alternante y habilidades visuoespaciales y visuoconstructivas.

Adverse events of targeted anticancer therapies: what radiologists need to know. / Efectos adversos de las terapias dirigidas contra el cáncer: lo que el radiólogo debe saber.

The treatment of cancer has improved drastically in recent decades. Better understanding of tumor biology has enabled the development of new treatments, called targeted therapy. These drugs target specific signaling pathways that are necessary for the development of cancer. Immunotherapy is even more novel. These new agents can be classified into different groups, mainly according to their mechanism of action: VEGF inhibitors or anti-angiogenic agents, EGFR inhibitors, mTOR inhibitors, CTLA-4 inhibitors, or PD-1/PD-L1 inhibitors, etc. All these new treatments are accompanied by new adverse effects that radiologists need to know. Understanding the molecular mechanisms of targeted therapies and knowing their adverse effects are vital to imaging assessment and ensuring appropriate treatment.

Hipointensidad cortical en secuencias eco de gradiente T2 en la leucoencefalopatía multifocal progresiva / Cortical hypointensity in T2-weighted gradient-echo sequences in patients with progressive multifocal leukoencephalopathy

INTRODUCCIÓN: La leucoencefalopatía multifocal progresiva (LMP) es una enfermedad desmielinizante del sistema nervioso central causada por la reactivación del virus JC. Esta encefalopatía oportunista se asocia mayormente a pacientes inmunodeprimidos con VIH en estadio III, y en los últimos años se ha asociado a tratamientos inmunosupresores como el natalizumab. La resonancia magnética (RM) tiene un papel importante tanto en el diagnóstico precoz como en el seguimiento de esta enfermedad. Recientemente, se han descrito en las secuencias eco de gradiente T2 (EGT2) y secuencias de susceptibilidad magnética (SWI) hipointensidades en las fibras-U y en la corteza adyacente a las lesiones de sustancia blanca características de la enfermedad. OBJETIVO: Nuestro objetivo es analizar la presencia y utilidad del signo de la hipointensidad cortical en secuencias EGT2 en relación con el diagnóstico de LMP, así como realizar una revisión bibliográfica sobre el tema. MATERIAL Y MÉTODOS: En este trabajo se analizan tres casos de LMP vistos en nuestro centro en 3 pacientes diferentes con inmunosupresión de distinto origen: uno con enfermedad por VIH en estadio III, otro con esclerosis múltiple en tratamiento con natalizumab y otro con artritis reumatoide en tratamiento con rituximab. RESULTADOS: En los tres casos se observa en la RM el hallazgo de hipointensidad cortical adyacente a la lesión de la sustancia blanca en la secuencia EGT2. En la paciente con esclerosis múltiple, este signo fue más precoz que la alteración de señal en la sustancia blanca. El paciente en tratamiento con rituximab fue diagnosticado post mortem y se presenta una correlación radiopatológica. CONCLUSIÓN: La hipointensidad cortical descrita en el EGT2 en los estudios de RM parece ser un hallazgo que apoyaría el diagnóstico de la LMP, independientemente del tipo de inmunosupresión, lo que nos hace plantear su inclusión de forma rutinaria entre los hallazgos a evaluar en RM en los pacientes con sospecha de LMP

INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by the reactivation of the JC virus. This opportunistic encephalopathy mainly affects immunodepressed patients with stage III HIV infection, although in recent years it has also been found in association with treatment with immunosuppressors such as natalizumab. MRI plays an important role in both the early diagnosis and follow-up of this disease. Recently, it has been reported that hypointensities in U-fibers and cortex adjacent to white-matter lesions characteristic of the disease can be identified on T2-weighted gradient-echo and susceptibility-weighted sequences in patients with progressive multifocal leukoencephalopathy. OBJECTIVE: We aimed to analyze the presence and usefulness of cortical hypointensity on T2-weighted gradient-echo sequences in relation to the diagnosis of progressive multifocal leukoencephalopathy and to review the literature on the topic. MATERIAL AND METHODS: We analyze three cases of progressive multifocal leukoencephalopathy seen at our center in three patients with immunosuppression of different origins: one with stage III HIV infection, one with multiple sclerosis being treated with natalizumab, and one with rheumatoid arthritis being treated with rituximab. RESULTS: In all three cases MRI showed the cortical hypointensity adjacent to the white-matter lesion in the T2-weighted gradient-echo sequence. In the patient with multiple sclerosis, this sign appeared earlier than the abnormal signal in the white matter. The patient being treated with rituximab was diagnosed postmortem and the pathology findings correlated with the MRI findings. CONCLUSION: The finding of cortical hypointensity on T2-weighted gradient-echo MRI sequences seems to support the diagnosis of progressive multifocal leukoencephalopathy, regardless of the type of immunosuppression, so this finding should routinely assessed in patients suspected of having this disease

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer.

BACKGROUND: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed. METHODS: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and re-interventions. RESULTS: Invasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%-96%) and disease free survival was 78% (95% CI: 69%-85%). CONCLUSIONS: Immediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome.

Cortical hypointensity in T2-weighted gradient-echo sequences in patients with progressive multifocal leukoencephalopathy. / Hipointensidad cortical en secuencias eco de gradiente T2 en la leucoencefalopatía multifocal progresiva.

INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by the reactivation of the JC virus. This opportunistic encephalopathy mainly affects immunodepressed patients with stage III HIV infection, although in recent years it has also been found in association with treatment with immunosuppressors such as natalizumab. MRI plays an important role in both the early diagnosis and follow-up of this disease. Recently, it has been reported that hypointensities in U-fibers and cortex adjacent to white-matter lesions characteristic of the disease can be identified on T2-weighted gradient-echo and susceptibility-weighted sequences in patients with progressive multifocal leukoencephalopathy. OBJECTIVE: We aimed to analyze the presence and usefulness of cortical hypointensity on T2-weighted gradient-echo sequences in relation to the diagnosis of progressive multifocal leukoencephalopathy and to review the literature on the topic. MATERIAL AND METHODS: We analyze three cases of progressive multifocal leukoencephalopathy seen at our center in three patients with immunosuppression of different origins: one with stage III HIV infection, one with multiple sclerosis being treated with natalizumab, and one with rheumatoid arthritis being treated with rituximab. RESULTS: In all three cases MRI showed the cortical hypointensity adjacent to the white-matter lesion in the T2-weighted gradient-echo sequence. In the patient with multiple sclerosis, this sign appeared earlier than the abnormal signal in the white matter. The patient being treated with rituximab was diagnosed postmortem and the pathology findings correlated with the MRI findings. CONCLUSION: The finding of cortical hypointensity on T2-weighted gradient-echo MRI sequences seems to support the diagnosis of progressive multifocal leukoencephalopathy, regardless of the type of immunosuppression, so this finding should routinely assessed in patients suspected of having this disease.