Characterisation and Outcomes of Patients with Solid Organ Malignancies Admitted to the Intensive Care Unit: Mortality and Impact on Functional Status and Oncological Treatment.

BACKGROUND: Despite the increasing number of ICU admissions among patients with solid tumours, there is a lack of tools with which to identify patients who may benefit from critical support. We aim to characterize the clinical profile and outcomes of patients with solid malignancies admitted to the ICU. METHODS: Retrospective observational study of patients with cancer non-electively admitted to the ICU of the Hospital Clinic of Barcelona (Spain) between January 2019 and December 2019. Data regarding patient and neoplasm characteristics, ICU admission features and outcomes were collected from medical records. RESULTS: 97 ICU admissions of 84 patients were analysed. Lung cancer (22.6%) was the most frequent neoplasm. Most of the patients had metastatic disease (79.5%) and were receiving oncological treatment (75%). The main reason for ICU admission was respiratory failure (38%). Intra-ICU and in-hospital mortality rates were 9.4% and 24%, respectively. Mortality rates at 1, 3 and 6 months were 19.6%, 36.1% and 53.6%. Liver metastasis, gastrointestinal cancer, hypoalbuminemia, elevated basal C-reactive protein, ECOG-PS greater than 2 at ICU admission, admission from ward and an APACHE II score over 14 were related to higher mortality. Functional status was severely affected at discharge, and oncological treatment was definitively discontinued in 40% of the patients. CONCLUSION: Medium-term mortality and functional deterioration of patients with solid cancers non-electively admitted to the ICU are high. Surrogate markers of cachexia, liver metastasis and poor ECOG-PS at ICU admission are risk factors for mortality.

Development and Independent Validation of a Prognostic Gene Expression Signature Based on RB1, PTEN, and TP53 in Metastatic Hormone-sensitive Prostate Cancer Patients.

BACKGROUND: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormone-sensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with an aggressive evolution and treatment resistance in castration-resistant prostate cancer (CRPC). OBJECTIVE: To study the clinical implications of TSG mRNA expression in mHSPC patients. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter retrospective biomarker study in mHSPC patients. TSGlow status was defined when two or more out of the three TSGs presented low RNA expression by nCounter in formalin-fixed paraffin-embedded samples and TSGwt for the remaining cases. The microarray data from the CHAARTED trial were analyzed as an independent validation cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular data were correlated with CRPC-free survival (CRPC-FS) and overall survival (OS) by the Kaplan-Meier method and multivariate Cox analysis. RESULTS AND LIMITATIONS: A total of 226 patients were included, of whom 218 were eligible: 93 were treated with ADT and 125 with ADT + D; 75.7% presented de novo stage IV and 67.9% high-volume disease. TSGlow (19.2%) was independently correlated with shorter CRPC-FS (hazard ratio [HR] 1.8, p = 0.002) and OS (HR 2, p = 0.002). In the CHAARTED trial, TSGlow was independently correlated with lower CRPC-FS (HR 2.2, p = 0.02); no differences in clinical outcomes according to treatment were observed in TSGlow patients, while a significant benefit was observed for ADT + D in the TSGwt group for CRPC-FS (HR 0.4, p < 0.001) and OS (HR 0.4, p = 0.001). However, no interaction was observed between TSG signature and treatment in either series. Study limitations are the retrospective design, small sample size, and lack of inclusion of patients treated with ADT + ART. CONCLUSIONS: TSGlow expression correlates with adverse outcomes in patients with mHSPC. The investigation of new therapeutic strategies in these patients is warranted. PATIENT SUMMARY: The low RNA expression of tumor suppressor genes in the tumors is correlated with adverse outcomes in patients with metastatic hormone-sensitive prostate cancer.

Epidemiology and risk factors for recurrence in biliary source bloodstream infection episodes in oncological patients.

We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906-7.503), biliary prosthesis (OR 2.232, 95% CI 1.157-4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338-8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389-5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

Mild forms of thrombotic microangiopathy in patients with advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel.

INTRODUCTION: Thrombotic microangiopathy (TMA) is an uncommon complication that may occur in cancer patients usually as an expression of cancer-associated coagulopathy or due to drug-related toxicity. The clinical spectrum of TMA may vary from an incidental laboratory finding in cancer outpatients to potentially severe life-threatening clinical forms with organ involvement requiring prompt recognition and multidisciplinary evaluation. CASE REPORTS: We present the clinical characteristics and outcomes of four patients with advanced pancreatic cancer with acute non-immune intravascular haemolysis compatible with microangiopathic acute haemolytic anaemia associated with mild thrombocytopenia during long-term gemcitabine and nab-paclitaxel treatment. MANAGEMENT AND OUTCOMES: Abnormal blood parameters (all four cases) and renal involvement (one case) were reversed with a conservative approach and chemotherapy discontinuation. One patient required a short hospitalization while the other three were managed as outpatients. The rapid reversibility of the blood abnormalities supported gemcitabine dose-related toxicity as the most likely aetiologic mechanism and demonstrates the current challenges in daily long-term cancer survivor care. DISCUSSION: Clinicians must take into account TMA in the differential diagnosis of acute anaemia with or without thrombocytopenia and organ damage, since adequate recognition and early treatment discontinuation allow effective outpatient management and favourable patient outcomes.

Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel.

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX.

A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes.

Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/ß-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches.

Radon and Lung Cancer: Current Trends and Future Perspectives.

Lung cancer is a public health problem and the first cause of cancer death worldwide. Radon is a radioactive gas that tends to accumulate inside homes, and it is the second lung cancer risk factor after smoking, and the first one in non-smokers. In Europe, there are several radon-prone areas, and although the 2013/59 EURATOM directive is aimed to regulate indoor radon exposition, regulating measures can vary between countries. Radon emits alpha-ionizing radiation that has been linked to a wide variety of cytotoxic and genotoxic effects; however, the link between lung cancer and radon from the genomic point of view remains poorly described. Driver molecular alterations have been recently identified in non-small lung cancer (NSCLC), such as somatic mutations (EGFR, BRAF, HER2, MET) or chromosomal rearrangements (ALK, ROS1, RET, NTRK), mainly in the non-smoking population, where no risk factor has been identified yet. An association between radon exposure and oncogenic NSCLC in non-smokers has been hypothesised. This paper provides a practical, concise and updated review on the implications of indoor radon in lung cancer carcinogenesis, and especially of its potential relation with NSCLC with driver genomic alterations.

Thrombotic microangiopathy (TMA) in adult patients with solid tumors: a challenging complication in the era of emerging anticancer therapies.

Thrombotic microangiopathy (TMA) is a syndrome that encompasses a group of disorders defined by the presence of endothelial damage leading to abnormal activation of coagulation, microangiopathic hemolytic anemia and thrombocytopenia, occlusive (micro)vascular dysfunction, and organ damage. TMA may occur in patients with malignancy as a manifestation of cancer-related coagulopathy itself or tumor-induced TMA (Ti-TMA) as a paraneoplastic uncommon manifestation of Trousseau syndrome. TMA can also be triggered by other overlapping conditions such as infections or more frequently as an adverse effect of anticancer drugs (drug-induced TMA or Di-TMA) due to direct dose-dependent toxicity or a drug-dependent antibody reaction. The clinical spectrum of TMA may vary widely from asymptomatic abnormal laboratory tests to acute severe potentially life-threatening forms due to massive microvascular occlusion. While TMA is a rare condition, its incidence may progressively increase within the context of the great development of anticancer drugs and the emerging scenarios in supportive care in cancer. The objective of the present narrative review is to provide a general perspective of the main causes, the key work-up clues that allow clinicians to diagnose and manage TMA in patients with solid tumors who develop anemia and thrombocytopenia due to frequent overlapping causes.

Functional gastrointestinal disorders frequency by Rome IV criteria.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs) are a very common pediatric disease, with strong implications for children and their families. We aimed to determine their frequency in our environment (per Rome IV criteria) and to establish if there is seasonal variability in diagnosis. METHODS: Descriptive, prospective study. For 12 months, children under 16 years of age with suspected FGIDs who had a first pediatric gastroenterology consultation were included and classified according to Rome IV criteria. Statistical analysis was done with SPSS v22. RESULTS: 574 children received consultations, 67% were >4 years of age. FGIDs were suspected in 44.6% of the patients, 32.4% were diagnosed according to Rome IV criteria (16.4% <4 years, 40.3% >4 years). 51.1% were female, average age of 8.4 ±â€¯4.2 years and mean of 7 months of symptoms until diagnosis (range 3-150). In patients <4 years, the most common disorders were functional constipation (48.4%), regurgitation (22.5%) and functional diarrhea (16.1%); in patients >4 years of age, functional abdominal pain (29%), functional dyspepsia (28.4%) and functional constipation (16.8%) were most frequent. We didn't discern seasonal variations in diagnosis in the global study population (p = 0.96) or by age group (<4 p = 0.51; >4 p = 0.57). CONCLUSIONS: FGIDs account for one third of our patients' consultations. While the Rome IV criteria are more inclusive than before, almost 30% of patients with suspected FGIDs don't meet said criteria. Although a seasonal difference regarding diagnosis was observed, it wasn't statistically significant either in the sample group as a whole or by age group.

Frecuencia de trastornos gastrointestinales funcionales según criterios Roma IV / Functional gastrointestinal disorders frequency by Rome IV criteria

Introducción: Los trastornos funcionales gastrointestinales (TFGI) son una enfermedad común en pediatría, con fuertes implicaciones para el niño y su familia. Nuestro objetivo es determinar su frecuencia en nuestro medio según criterios Roma IV y la posible variación estacional al diagnóstico. Material y métodos: Estudio descriptivo con recogida de información prospectiva. Durante un año se incluyó a menores de 16 años que acudieron a primera consulta de Gastroenterología Pediátrica con sospecha de TFGI, a los que se clasificó según Roma IV. Análisis estadístico mediante SPSS v22. Resultados: Acudieron en total 574 niños, el 67% mayores de 4 años. Se sospechó TFGI en el 44,6%, siendo diagnosticados según criterios Roma IV el 32,4% (16,4% <4 años, 40,3%> 4 años). El 51,1% eran mujeres, edad media de 8,4± 4,2 años y mediana de 7 meses de síntomas al diagnóstico (rango: 3-150). Por frecuencia, en <4 años destacan el estreñimiento (48,4%), la regurgitación (22,5%) y la diarrea funcional (16,1%), y en> 4 años el dolor abdominal funcional no especificado (29%), la dispepsia funcional (28,4%) y el estreñimiento (16,8%). En el diagnóstico por trimestres no se objetivaron diferencias en el total (p=0,96) ni por grupos de edad (< 4 años, p=0,51;> 4 años, p=0,57) Conclusión: Según Roma IV, los TFGI suponen un tercio de los pacientes de nuestra consulta. A pesar de ser más inclusivos que previamente, casi un 30% de los pacientes con sospecha no cumple criterios. Aunque existe cierta variación estacional en la frecuencia diagnóstica, no fue significativa ni en el total ni por grupos de edad. (AU)

Introduction: Functional gastrointestinal disorders (FGIDs) are a very common pediatric disease, with strong implications for children and their families. We aimed to determine their frequency in our environment (per Rome IV criteria) and to establish if there is seasonal variability in diagnosis. Material and methods: Descriptive, prospective study. For 12 months, children under 16 years of age with suspected FGIDs who had a first pediatric gastroenterology consultation were included and classified according to Rome IV criteria. Statistical analysis was done with SPSS v22. Results: 574 children received consultations, 67% were >4 years of age. FGIDs were suspected in 44.6% of the patients, 32.4% were diagnosed according to Rome IV criteria (16.4%, <4 years; 40.3%, >4 years). 51.1% were female, average age of 8.4±4.2 years and mean of 7 months of symptoms until diagnosis (range 3–150). In patients <4 years, the most common disorders were functional constipation (48.4%), regurgitation (22.5%) and functional diarrhea (16.1%); in patients >4 years of age, functional abdominal pain (29%), functional dyspepsia (28.4%) and functional constipation (16.8%) were most frequent. We did not discern seasonal variations in diagnosis in the global study population (p=.96) or by age group (< 4, P=.51; > 4, P=.57). Conclusions: FGIDs account for one third of our patients’ consultations. While the Rome IV criteria are more inclusive than before, almost 30% of patients with suspected FGIDs do not meet said criteria. Although a seasonal difference regarding diagnosis was observed, it was not statistically significant either in the sample group as a whole or by age group. (AU)

Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. METHODS: The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. RESULTS: In total, 1,536 subjects were evaluated; 58.4% (n = 894) had a PE and 7% (n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies (p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42-3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p = 0.0016). CONCLUSION: Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors.

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p < 0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46-8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

[Functional gastrointestinal disorders frequency by Rome IV criteria]. / Frecuencia de trastornos gastrointestinales funcionales según criterios Roma IV.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs) are a very common pediatric disease, with strong implications for children and their families. We aimed to determine their frequency in our environment (per Rome IV criteria) and to establish if there is seasonal variability in diagnosis. MATERIAL AND METHODS: Descriptive, prospective study. For 12 months, children under 16 years of age with suspected FGIDs who had a first pediatric gastroenterology consultation were included and classified according to Rome IV criteria. Statistical analysis was done with SPSS v22. RESULTS: 574 children received consultations, 67% were >4 years of age. FGIDs were suspected in 44.6% of the patients, 32.4% were diagnosed according to Rome IV criteria (16.4%, <4 years; 40.3%, >4 years). 51.1% were female, average age of 8.4±4.2 years and mean of 7 months of symptoms until diagnosis (range 3-150). In patients <4 years, the most common disorders were functional constipation (48.4%), regurgitation (22.5%) and functional diarrhea (16.1%); in patients >4 years of age, functional abdominal pain (29%), functional dyspepsia (28.4%) and functional constipation (16.8%) were most frequent. We did not discern seasonal variations in diagnosis in the global study population (p=.96) or by age group (< 4, P=.51; > 4, P=.57). CONCLUSIONS: FGIDs account for one third of our patients' consultations. While the Rome IV criteria are more inclusive than before, almost 30% of patients with suspected FGIDs do not meet said criteria. Although a seasonal difference regarding diagnosis was observed, it was not statistically significant either in the sample group as a whole or by age group.

Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice.

Progressive motor alterations and selective death of striatal medium spiny neurons (MSNs) are key pathological hallmarks of Huntington's disease (HD), a neurodegenerative condition caused by a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene. Most research has focused on the pathogenic effects of the resultant protein product(s); however, growing evidence indicates that expanded CAG repeats within mutant HTT mRNA and derived small CAG repeat RNAs (sCAG) participate in HD pathophysiology. The individual contribution of protein versus RNA toxicity to HD pathophysiology remains largely uncharacterized and the role of other classes of small RNAs (sRNA) that are strongly perturbed in HD is uncertain. Here, we demonstrate that sRNA produced in the putamen of HD patients (HD-sRNA-PT) are sufficient to induce HD pathology in vivo. Mice injected with HD-sRNA-PT show motor abnormalities, decreased levels of striatal HD-related proteins, disruption of the indirect pathway, and strong transcriptional abnormalities, paralleling human HD pathology. Importantly, we show that the specific blockage of sCAG mitigates HD-sRNA-PT neurotoxicity only to a limited extent. This observation prompted us to identify other sRNA species enriched in HD putamen with neurotoxic potential. We detected high levels of tRNA fragments (tRFs) in HD putamen, and we validated the neurotoxic potential of an Alanine derived tRF in vitro. These results highlight that HD-sRNA-PT are neurotoxic, and suggest that multiple sRNA species contribute to striatal dysfunction and general transcriptomic changes, favoring therapeutic strategies based on the blockage of sRNA-mediated toxicity.

Development of ossification in the vertical semicircular canals: tomographic study.

PURPOSE: To describe the ontogeny of vertical semicircular canals using computed tomography. MATERIALS AND METHODS: We have studied 39 human fetuses aged between 17 and 38 weeks of development through multi-helicoidal CT. RESULTS: The first signs of ossification in the semicircular canals, superior and posterior, are from 19 weeks of development, through two primary ossification centers in each canal, which will take part in the formation of the outer cover oriented towards the middle and posterior brain fossae, respectively. In this process it must be added the intervention of the common branch. Internal bone covers are formed by ossification of the fossa subarcuata in the superior semicircular canal, and from the compact center of the labyrinthine capsule into the posterior canal. The tomographic study has allowed us to demonstrate how ossification follows a variable rate, establishing a period between 21 and 26 weeks where there are completely closed canals with others still open to the brain fossae. CONCLUSIONS: The tomographic study of the semicircular canals has enabled us to establish a critical period in its ossification that could explain the etiology of the congenital-type dehiscence.

Fibrosis retroperitoneal idiopática / Idiopathic retroperitoneal fribrosis

OBJETIVO: Presentamos el caso de una Fibrosis retroperitoneal idiopática en un varón de 34 años, con antecedentes de anemia y elevación de la velocidad de sedimentación eritrocitaria. MÉTODO: Se realizó estudio con técnicas de imagen (ecografía, TC y RM) y posterior estudio anatomopatológico. RESULTADOS: Se evidenció por métodos de imagen (ecografía, TC y RM) una masa de características infiltrantes circunscrita a la porción superior del abdomen, diagnosticada tras su exéresis y estudio histológico e inmunohistoquímico de retroperitonitis esclerosante. CONCLUSION: La fibrosis retroperitoneal idiopática o enfermedad de Ormond es una enfermedad rara, de etiología oscura, caracterizada por marcada fibrosis del retroperitoneo, con un infiltrado inflamatorio constituido por células plasmáticas, linfocitos y eosinófilos. El interés de este caso recae en la localización atípica de la FRI, así como su presentación en un hombre joven, sin antecedentes de interés, llamando únicamente la atención la anemia y el aumento de la velocidad de sedimentación eritrocitaria en la analítica (AU)

Carcinoma indiferenciado del maxilar superior tipo rabdoide / Maxillary undifferentiated carcinoma with rhabdoid features

El denominado tumor rabdoide maligno fue individualizado por Haas y cols. como entidad propia, dentro de las neoplasias malignas del riñón, en 1981. A partir de las características histopatológicas del mismo fueron documentándose diferentes casos de tumor rabdoide extrarrenal. También se ha reconocido este aspecto en un heterogéneo grupo de neoplasias (carcinoma, melanoma, mesotelioma, y tumores mesenquimales). Microscópicamente, se observa una proliferación de células epitelioides de gran núcleo desplazado por abundantes filamentos intermedios, nucléolos prominentes y abundante citoplasma eosinófilo. En el presente trabajo se documenta el caso de un varón de 50 años con un tumor maligno del maxilar superior, con características histológicas de tumor rabdoide. Se discute su diagnóstico diferencial y se revisa la literatura sobre el tema (AU)

Tetraphosphacubane: An Unexpectedly Strong Base in the Gas Phase.

The experimental determination of physical properties of tetra-tert-butylphosphocubane (TtBuPC) is of paramount importance for understanding the reactivity of this fascinating molecule.The gas-phase basicity of TtBuPC measured by FT-ICR spectroscopy (GB = 221.8 kcal mol(-)(1), PA = 230.5 kcal mol(-)(1)) is surprisingly high although protonation in solution is only achieved under drastic conditions. A molecular orbital treatment, including electron correlation effects, predicts the unsubstituted parent compound phosphacubane (PC) to be a carbon base. Carbon protonation implies a P-C bond fission which alleviates the strain of the system. A similar behavior is also predicted for the tetramethyl derivative. However, TtBuPC is found to be a phosphorus base, because the strong repulsive interactions which appear between the tert-butyl substituents destabilize significantly the C-protonated form. These effects decrease dramatically when just one tert-butyl group is removed and both P- and C-protonated species become almost degenerate. As for other strained systems, the PAs of PC and TtBuPC are only adequately reproduced when G2-type [6-311+G(3df,2p)] basis sets are used.