Beyond Benign: A Case of Subependymal Giant Cell Astrocytomas Provoking Hydrocephalus in Tuberous Sclerosis Complex.

22-year-old male diagnosed with Tuberous Sclerosis Complex (TSC), a genetic disorder characterized by benign tumors in various organs, with a focus on neurological implications. Central to the study is the development of Subependymal Giant Cell Astrocytomas (SEGAs), leading to hydrocephalus in the patient. The diagnosis of TSC was made in the patient's childhood, and he was monitored regularly. The study highlights a significant growth in a subependymal nodule, leading to monoventricular hydrocephalus. MRI scans played a crucial role in identifying the progression of SEGAs and the subsequent hydrocephalus. The treatment approach involved endoscopic surgical removal of the SEGA, with histopathology confirming the diagnosis. Post-surgical outcomes over an eight-year follow-up period showed a normalization in ventricular size and the stability of other subependymal nodules, without any complications. This case underscores the importance of regular monitoring for TSC patients, early intervention for complications like hydrocephalus, and the need for a multidisciplinary treatment approach. The case study provides valuable insights into the management of neurodevelopmental disorders and the complexities surrounding TSC and SEGAs.

Approach to the so-called "Invisible Dermatosis": When Subtle Histopathological Findings Guide Diagnosis.

ABSTRACT: Invisible dermatosis is a concept that can be applied either to clinical or histopathological findings. We will focus on the dermatopathological aspect of this invisible dermatosis that can be seen as dermatosis with subtle histopathological findings that are mandatory to known to stablish the diagnosis. With a proper approach facing in depth the different skin layers from stratum corneum to subcutaneous tissue combined with some especial stains, special investigations and mostly a proper clinicopathological correlation, the problem of missing out a diagnosis can be decreased. We will review the general aspects for diagnosis and the peculiar findings of an in-depth review of them because it is important to note that minor changes on a skin biopsy do not mean it is disease free. We will review classic clues, we will add some new useful ones, and we will also provide a guide on the special stains helpful, such as periodic acid-Schiff when facing fungi, orcein-Giemsa and van Gieson when altered elastic fibers are suspected, or Pearl and Masson Fontana when an altered skin pigmentation is suspected.

Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group.

INTRODUCTION: Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. MATERIALS AND METHODS: Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. RESULTS: Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. CONCLUSION: Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.

Breast Cancer Patient with Li-Fraumeni Syndrome: A Case Report Highlighting the Importance of Multidisciplinary Management.

Germline mutations in TP53, a tumor suppressor gene, are involved in the development of Li-Fraumeni syndrome, a rare disorder that predisposes carriers to multiple tumors. TP53 mutations have been associated with resistance to treatment and poor prognosis. A young female with the pathogenic germline TP53 mutation c.844C > T (p.R282W) was diagnosed with two metachronous breast tumors, one HER2-negative and the other HER2-positive. She was later diagnosed with synchronous glioblastoma, epidermal growth factor receptor-mutated lung adenocarcinoma, and HER2-negative breast cancer metastases. The patient was treated with local therapies, including brain surgery and radiotherapy, lung surgery, and a bilateral mastectomy, as well as with targeted systemic treatment. She proved to be highly sensitive to systemic therapy, and 13 years after the initial diagnosis of breast cancer and 6 years after the diagnosis of the two new primary tumors and recurrence of a prior cancer, she is alive with an excellent performance status. This surprising positive evolution may well be partly due to the pronged multidisciplinary approach to managing her disease and her extraordinary response to treatment: the lung adenocarcinoma showed excellent response to erlotinib; the breast cancer responded extremely well to eribulin and pegylated liposomal doxorubicin; and the glioblastoma has remained in response to surgery and radiotherapy. Despite harboring a TP53 mutation and having multiple tumors, this patient has shown an unexpectedly favorable evolution. The coordinated participation of a multidisciplinary team and the patient's own extraordinarily high sensitivity to systemic treatment played a major role in this evolution.

Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients: FN14 and GRP94 from Diagnosis to Prophylaxis.

FN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to stratify breast cancer patients according their risk of brain metastasis (BrM) progression. We analyzed FN14 and GRP94 by immunohistochemistry in a retrospective multicenter study using tissue microarrays from 208 patients with breast carcinomas, of whom 52 had developed BrM. Clinical and pathological characteristics and biomarkers expression in Luminal and non-Luminal patients were analyzed using a multivariate logistic regression model adjusted for covariates, and brain metastasis-free survival (BrMFS) was estimated using the Kaplan-Meier method and the Cox proportional hazards model. FN14 expression was associated with BrM progression mainly in Luminal breast cancer patients with a sensitivity (53.85%) and specificity (89.60%) similar to Her2 expression (46.15 and 89.84%, respectively). Moreover, the likelihood to develop BrM in FN14-positive Luminal carcinomas increased 36.70-fold (3.65-368.25, p = 0.002). Furthermore, the worst prognostic factor for BrMFS in patients with Luminal carcinomas was FN14 overexpression (HR = 8.25; 95% CI: 2.77-24.61; p = 0.00015). In these patients, GRP94 overexpression also increased the risk of BrM (HR = 3.58; 95% CI: 0.98-13.11; p = 0.054-Wald test). Therefore, FN14 expression in Luminal breast carcinomas is a predictive/prognostic biomarker of BrM, which combined with GRP94 predicts BrM progression in non-Luminal tumors 4.04-fold (1.19-8.22, p = 0.025), suggesting that both biomarkers are useful to stratify BrM risk at early diagnosis. We propose a new follow-up protocol for the early prevention of clinical BrM of breast cancer patients with BrM risk.

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.

Políticas sanitarias locales puestas a prueba: consultores, expertos, misiones internacionales y poliomielitis en España, 1950-1975 / Local health policies under the microscope: consultants, experts, international missions and poliomyelitis in Spain, 1950-1975

Este trabajo analisa las misiones de expertos de organismos sanitarios internacionales en España destinadas a informar sobre la situación, las actividades realizadas y las intervenciones necesarias en la lucha contra la discapacidad física de los niños. El Plan España-23 fue el instrumento utilizado por la OMS y otras agencias para poner en marcha el proceso de cambio en un país en transformación durante la larga etapa de vigencia de la dictadura franquista. El trabajo utiliza como fuentes informes inéditos de expertos de la OMS, que fueron resultado de visitas realizadas al país entre 1950 y 1975. El abordaje metodológico consistió en un análisis del discurso que se encuentra en las fuentes y su contextualización en los marcos historiográficos pertinentes.

One of the main focuses of analysis of this paper concerns the missions of international health agency experts to Spain to report on the situation, the activities in the fight against physical disabilities in children and on the actions taken to cope with the problem. The Spain-23 Plan was the instrument used by WHO and other agencies to start the process of change in a country undergoing a period of transformation under the enduring Franco dictatorship. As key sources, the paper uses unpublished reports of WHO experts on the subject, which resulted from visits to the country between 1950 and 1975. The methodological approach consists of an analysis of discourses from primary sources within the historiographical framework.

Información, autoayuda y creación de identidades: las tecnologías de la información y la comunicación (TIC) y las asociaciones de discapacitados físicos. El ejemplo de la poliomielitis / Information, self-help and identity creation: information and communication technologies (ICTs) and associations for the physically disabled. The example of poliomyelitis

El objetivo del trabajo es estudiar la calidad de las páginas web de asociaciones de personas afectadas por poliomielitis y síndrome postpolio, como uno de los sistemas de intercambio de información y de visibilidad social de las personas con discapacidades físicas. Se realizó un estudio descriptivo de carácter transversal; fueron evaluadas 375 páginas web que cumplían los criterios de inclusión, encontradas a través del motor de búsqueda Google. La calidad fue estudiada a través de 22 variables, 8 de las cuales conforman el "Indicador de Credibilidad". Ninguna de las páginas cumplió con todos los criterios de calidad ni con los 8 puntos del Indicador de Credibilidad. Se observa una correlación positiva entre las variables de calidad y los criterios de credibilidad (r de Pearson = 0,81, p<0,001), por lo que se sugiere el Indicador de Credibilidad como una herramienta útil para determinar la calidad de las páginas web. Su uso debe complementarse con otro tipo de acercamientos cualitativos que exploren el contexto de las relaciones expertos-legos y las funciones que dichas páginas cumplen.

The aim of this paper is to study the quality of the websites of associations for people with polio and post-polio syndrome as an example of an important method for exchanging information and promoting the social visibility of physically disabled people. A descriptive cross-sectional study of 375 sites that met inclusion criteria, found using of the Google search engine, was carried out. The quality was studied through 22 variables, 8 of which make up the "Credibility Indicator". None of the websites met all the quality criteria nor all 8 items in the Credibility Index. A positive correlation between the variables of quality and credibility criteria (Pearson r = 0.81, p<0.001) was observed, therefore the Credibility Index is suggested as a useful tool for determining the quality of the websites. However, this tool must be supplemented with other qualitative approaches that explore both the contexts of lay-expert relationships and the function these sites serve.

Los medios de comunicación al servicio de la lucha antivenérea y la protección de la salud materno-infantil (1900-50) / The mass media at the service of the fight against venereal diseases and the protection of maternal-infant health (1900-50)

En este artículo pretendemos analizar el uso del cartelismo sanitario en el contexto de las campañas de educación sanitaria que las instituciones sanitarias españolas diseñaron para difundir conocimientos científico-técnicos, influir en las actitudes e intentar modificar comportamientos en la población española. Nos centramos en los carteles relacionados con la protección de la salud materno-infantil y las enfermedades venéreas. La investigación analiza igualmente la utilización del cartelismo como instrumento para atraer pacientes a los servicios sanitarios. También se pretende analizar su contribución, junto a otros muchos factores, a la construcción de determinadas imágenes de la maternidad, de la infancia sana, de género y sexualidad en el marco del desarrollo de la salud pública española.

Phase II study of temozolomide and cisplatin as primary treatment prior to radiotherapy in newly diagnosed glioblastoma multiforme patients with measurable disease. A study of the Spanish Medical Neuro-Oncology Group (GENOM).

UNLABELLED: This phase II study evaluates the activity of temozolomide and cisplatin administered before radiation therapy in newly diagnosed glioblastoma multiforme patients, in terms of response, time to progression and survival. PATIENTS AND METHODS: Forty patients with measurable disease after surgery, a Karnofsky status > 60, and Barthel Index > 10 were included. They were treated with three cycles of temozolomide 200 mg/m2/day for 5 days and cisplatin 100 mg/m2 on day 1. Conventional focal radiation therapy to 60 Gy was administered after response evaluation. RESULTS: Three patients were not evaluable for central reviewed response but all 40 were evaluable for toxicity, time to progression and survival. Objective responses by Macdonald criteria on an intent to treat basis were 45% including complete response in three patients (7.5%), and partial response in 15 patients (37.5%). Responses were seen in biopsy-only patients (33.4%) as well as in partial surgery patients (52%). Median survival for all patients was 12.5 months. Biopsy-only patients had a median survival of 12.8 months. Grade 3 to 4 neutropenia was the most important toxicity, and occurred in 37.5% of patients. A delay in 18.2% and a dose reduction in 9.6% of cycles were necessary due to myelosuppression on day 28. Two patients had neutropenic fever resulting in one treatment-related death. Eighty-two percent of patients received radiotherapy. CONCLUSION: This regimen has significant activity, as it induces objective responses even in biopsy-only patients, appearing to improve their median survival. A better combination schedule is needed to improve the toxicity profile.

O6-methyl-guanine-DNA methyltransferase methylation in serum and tumor DNA predicts response to 1,3-bis(2-chloroethyl)-1-nitrosourea but not to temozolamide plus cisplatin in glioblastoma multiforme.

PURPOSE: In glioblastoma multiforme (GBM), the cytotoxic effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolamide is dependent on O(6) alkylation, which correlates inversely with expression of the DNA repair enzyme O(6)-methyl-guanine-DNA methyltransferase (MGMT). Thus, MGMT assessment can be useful in predicting response in GBM, but the scarcity of neoplastic cells limits the practicality of MGMT assessment in these tumors. Although GBM grows within the skull, we investigated the concordance of methylation in glioma tissue, and paired serum DNA and the potential correlation with response and time to progression. EXPERIMENTAL DESIGN: Using MSP assay, we assessed the methylation of MGMT, p16, DAPK, and RASSF1A in tumor and serum DNA from 28 GBM patients treated with BCNU or with temozolamide plus cisplatin. RESULTS: The concordance between methylation in tumor and serum was highly significant. Overall, response plus stable disease was noted in 10 of 11 (90.9%) patients with MGMT methylation and in 5 of 14 (35.7%) patients without (P = 0.01). In the 16 patients treated with temozolamide plus cisplatin, no significant correlation between MGMT methylation status and response was observed, whereas in BCNU-treated patients, a significant difference was observed in favor of those with methylated MGMT. Time to progression was 29.9 weeks in 12 patients with MGMT methylation and 15.7 weeks in 10 patients without (P = 0.006). No correlation was observed between response or time to progression and p16, DAPK, or RASSF1A methylation. CONCLUSIONS: Methylated MGMT, p16, DAPK, and RASSF1A were found in serum DNA of GBM patients, with a good correlation between serum and primary tumor tissue. Serum MGMT methylation predicted response and time to progression in BCNU-treated GBM patients. The methylation-specific PCR assay in serum DNA could be a good predictive tool for selecting GBM patients to be treated with BCNU or alternatively with the combination of temozolamide plus cisplatin.