Genome-wide CRISPR/Cas9 library screening identified ATM signaling network genes as critical drivers for resistance to ATR inhibition in soft-tissue sarcomas: synthetic lethality and therapeutic implications.

Soft-tissue sarcoma (STS) are a heterogeneous group of rare tumors with different biological behavior that are fatal in more than 40% of cases, due to their metastatic evolution and inadequate treatment options. ATR inhibition already showed an activity, even if modest, in broad pre-clinical models of STS. By using genome-wide CRISPR/Cas9 library screening, we identified ATM signaling network genes as critical drivers for resistance to the specific ATR inhibitor AZD6738. The role of such genes in resistance to AZD6738 was confirmed by using CRISPR/Cas9 knockout models. More strikingly, the ATM inhibitor AZD0156 works synergistically with AZD6738 in vitro and abolishes STS growth in vivo in our models of most frequent histotypes (such as dedifferentiated liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma among others). Moreover, the combination of AZD6738 and AZD0156 induced significantly higher levels of DNA damage than either drug used as single agent alone. In summary, our results demonstrate that targeting ATM is an effective approach to overcome resistance to ATR inhibition in different STS subtypes, including the most frequent histologies.

Differences in innate fear behaviour in native Japanese chickens.

1. Comprehensive knowledge of innate fear in chickens has important implications for understanding the adaptation of native Japanese chickens in modern production and behavioural changes caused by modern breeding goals. Innate fear behaviour seen in chicks from six native Japanese chicken breeds;, Ingie (IG), Nagoya (NAG), Oh-Shamo (OSM), Tosa-Jidori (TJI), Tosa-Kukin (TKU) and Ukokkei (UK), were compared with those in two lines of White Leghorn (WL-G and WL-T) in tonic immobility (TI) and open field (OF) tests.2. TI and OF tests were conducted for 267 chicks at 0-1 days of age in the eight breeds. Raw data for four TI traits and 13 OF traits were corrected for environmental factors. Breed differences were analysed by the Kruskal-Wallis test followed by the Steel Dwass post hoc test. Principal component (PC) analyses were conducted.3. The results showed that OSM was the least sensitive to fear in both the TI and OF tests. The WL-G birds showed higher sensitivity to TI fear but lower sensitivity to OF fear. The PC analysis of OF traits classified the tested breeds into three groups: least (OSM and WL-G), moderate (IG, WL-T, NAG, TJI and TKU) and most sensitive (UK).

Health lifestyles during adolescence: clustering of health behaviours and social determinants in Italian adolescents.

BACKGROUND: Health behaviours in adolescence have a high impact on both current and future health. The literature claims a focus on social determinants and shows that these behaviours are associated. The concept of 'health lifestyles' should be considered to account for co-occurring health behaviours and determinants interactions. The aim of this study is to increase our understanding of adolescents' health lifestyles and to (i) cluster adolescents according to a comprehensive number of health behaviours and (ii) describe these groups according to sociodemographic characteristics, perceptions of life contexts (family, school, peers or neighbourhood) and perceived physical and psychosocial health conditions. METHODS: In Italy, 906 15-year-old students participated in the cross-national Health Behaviour of School-aged Children study. Clusters were identified by applying the KAMILA clustering method and compared using analysis of variance and chi-squared tests.Results: Four clusters were identified: 'substance consumers', 'media lovers', 'active students' and 'passive students'. Each cluster exhibited different characteristics related to health behaviours and social determinants. CONCLUSIONS: Interesting associations between health behaviours were identified, which showed the relevance of considering the adolescents' overall lifestyles. The description of each cluster permitted the identification of risks and protective factors, which may be important for designing effective health promotion activities.

An immunological signature to predict outcome in patients with triple-negative breast cancer with residual disease after neoadjuvant chemotherapy.

BACKGROUND: When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse. MATERIALS AND METHODS: We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors. RESULTS: Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC). CONCLUSIONS: Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis.

Life skill education at the time of COVID-19: perceptions and strategies of Italian expert school educators.

The coronavirus disease 2019 (COVID-19) pandemic has had a huge effect on adolescents' health and learning. Health promotion strategies should be valued, and life skill education is a potential approach in this direction. This study aimed to investigate the implementation of an evidence-based life skill education programme during the COVID-19 pandemic in the Lombardy Region (Italy) by collecting opinions about the programme's usefulness and feasibility and identifying the strategies for implementing it through distance teaching. The study involved 63 middle school expert teachers, principals or coordinators in life skill education. An online questionnaire with closed- and open-ended questions was used. A qualitative content analysis was carried out using N-Vivo Answers software. The participants recognized the high value of life skill education at the time of COVID-19, but they showed reticence regarding its feasibility. Positive effects of the programme on both health and learning outcomes were reported. The obstacles were related to interpersonal aspects, student involvement, methods, organization and planning. Many strategies were suggested related to the teaching method, the curriculum organization and the adaptation needs. These strategies can be used to implement active and cooperative learning at a distance to reinforce students' life skills to cope with the crisis and promote their health.

GSK3-beta as a candidate therapeutic target in soft tissue sarcomas.

Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3ß (GSK-3ß) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3ß gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.

Antibiotic-resistant Staphylococcus aureus strains of swine origin: molecular typing and susceptibility to oregano (Origanum vulgare L.) essential oil and maqui (Aristotelia chilensis (Molina) Stuntz) extract.

AIM: The molecular typing and the susceptibility of Staphylococcus aureus strains of swine origin to antibiotics, oregano (Origanum vulgare L.) essential oil (EO) and Chilean blackberry maqui (Aristotelia chilensis (Molina) Stuntz) extract were determined. METHODS AND RESULTS: Twenty S. aureus strains of swine origin were subjected to molecular typing, of which six strains were selected for antimicrobial susceptibility testing. The epsilon test (Etest) was used to determine the antibiotic susceptibility. The susceptibility to natural antimicrobials (NAs): oregano EO, maqui extract, thymol (Thy) and carvacrol (Carv), was carried out using the disk diffusion method. The S. aureus strains were genetically diverse. All strains were resistant to at least one class of antibiotic, and two strains were multidrug-resistant. The minimum inhibitory concentration of oregano EO, Thy and Carv was 0·01-0·04%. Maqui extract did not show antistaphylococcal activity. CONCLUSIONS: Natural antimicrobials extracted from oregano have an inhibitory activity against S. aureus strains from swine origin, with no effect using maqui extract. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information about the characteristics of S. aureus strains of swine origin, and about the potential use of NAs from oregano to enhance the control of antibiotic-resistant S. aureus strains in the pork supply chain.

CHK1 inhibition in soft-tissue sarcomas: biological and clinical implications.

Background: Inhibition of ChK1 appears as a promising strategy for selectively potentiate the efficacy of chemotherapeutic agents in G1 checkpoint-defective tumor cells such as those that lack functional p53 protein. The p53 pathway is commonly dysregulated in soft-tissue sarcomas (STS) through mutations affecting TP53 or MDM2 amplification. GDC-0575 is a selective ATP-competitive inhibitor of CHK1. Methods: We have performed a systematic screening of a panel of 10 STS cell lines by combining the treatment of GDC-0575 with chemotherapy. Cell proliferation, cell death and cell cycle analysis were evaluated with high throughput assay. In vivo experiments were carried out by using TP53-mutated and TP53 wild-type patient-derived xenograft models of STS. Clinical activity of GDC-0575 combined with chemotherapy in patients with TP53-mutated and TP53 wild-type STS was also assessed. Results: We found that GDC-0575 abrogated DNA damage-induced S and G2-M checkpoints, exacerbated DNA double-strand breaks and induced apoptosis in STS cells. Moreover, we observed a synergistic or additive effect of GDC-0575 together with gemcitabine in vitro and in vivo in TP53-proficient but not TP53-deficient sarcoma models. In a phase I study of GDC-0575 in combination with gemcitabine, two patients with metastatic TP53-mutated STS had an exceptional, long-lasting response despite administration of a very low dose of gemcitabine whereas one patient with wild-type TP53 STS had no clinical benefit. Genetic profiling of samples from a patient displaying secondary resistance after 1 year showed loss of one preexisting loss-of-function mutation in the helical domain of DNA2. Conclusion: We provide the first preclinical and clinical evidence that potentiation of chemotherapy activity with a CHK1 inhibitor is a promising strategy in TP53-deficient STS and deserves further investigation in the phase II setting.

Factores fisiopatológicos y metas terapéuticas perioperatorias que influyen en procedimientos quirúrgicos reconstructivos mediante colgajos en pacientes con Diabetes Mellitus / Pathophysiologic factors and perioperative therapeutic goals that affect reconstructive surgical procedures with flaps in patients with Diabetes Mellitus

RESUMEN Introducción: la diabetes mellitus es considerada un factor de riesgo para complicaciones locales y fracaso quirúrgico en cirugías reconstructivas mediante el uso de colgajos debido a las alteraciones en el proceso de cicatrización propias de esta patología. Objetivo: hacer una revisión de la literatura disponible sobre los factores fisiopatológicos que influyen en los resultados posquirúrgicos a corto, mediano y largo plazo en la población diabética, así como de las metas terapéuticas perioperatorias asociadas a mayores tasas de éxito. Metodología de Búsqueda: se realizó búsqueda en las bases de datos PUBMED, MEDLINE Y SCIELO, mediante el gestor de búsqueda utilizando los términos: "Period perioperative", "Reconstructive surgical procedures", "Surgical flaps", "Diabetes mellitus", obteniendo un total de 160 artículos de revistas en línea, de los cuales se seleccionaron 50. Resultados: la realización de colgajos en pacientes con diabetes mellitus se asocia a mayor riesgo de fracaso y complicaciones, las cuales disminuyen considerablemente si se realiza un estricto manejo perioperatorio enfocado en metas. Conclusiones: la diabetes mellitus causa alteraciones en la respuesta inflamatoria, disfunción microvascular y mayor estrés oxidativo, lo cual se ve reflejado en un proceso de cicatrizacion anormal, generando mayores tasas de infeccion y perdidas de colgajos; un estricto manejo peri operatorio guiado por metas logra disminuir las complicaciones y aumentar el exito quirurgico. MÉD.UIS. 2017;30(1):35-43.

ABSTRACT Introduction: diabetes mellitus is considered a risk factor for local complications and surgical failure in reconstructive surgeries, mainly in flaps due to the fact that it causes alterations in the cicatrization process. Objective: to review the available literature on the pathophysiological factors that influence the short-, medium- and long-term results in the diabetic population, the perioperative therapeutic goals associated with higher success rates, and to establish a baseline protocol for the perioperative management of these patients. Searching methodology: we searched the PUBMED, MEDLINE and SCIELO databases using the search terms "Period perioperative", "Reconstructive surgical procedures", "Surgical flaps", "Diabetes mellitus", obtaining a total of 160 online journal articles, of which 50 were selected. Results: the performance of flaps in patients with diabetes mellitus is associated with an increased risk of failure and complications, which decrease considerably when a strict goal-directed perioperative management is performed. Conclusions: diabetes mellitus causes alterations in the inflammatory response, microvascular dysfunction and increases oxidative stress, which is reflected in an abnormal healing process, generating higher infection rates and graft loss, but if glycemic management goals are achieved in the perioperative period it is possible to reduce the complications and to increase the surgical success. MÉD.UIS. 2017;30(1):35-43.

Parity-Time Synthetic Phononic Media.

Classical systems containing cleverly devised combinations of loss and gain elements constitute extremely rich building units that can mimic non-Hermitian properties, which conventionally are attainable in quantum mechanics only. Parity-time (PT) symmetric media, also referred to as synthetic media, have been devised in many optical systems with the ground breaking potential to create nonreciprocal structures and one-way cloaks of invisibility. Here we demonstrate a feasible approach for the case of sound where the most important ingredients within synthetic materials, loss and gain, are achieved through electrically biased piezoelectric semiconductors. We study first how wave attenuation and amplification can be tuned, and when combined, can give rise to a phononic PT synthetic media with unidirectional suppressed reflectance, a feature directly applicable to evading sonar detection.

Bulk and surface acoustic waves in solid-fluid Fibonacci layered materials.

We study theoretically the propagation and localization of acoustic waves in quasi-periodic structures made of solid and fluid layers arranged according to a Fibonacci sequence. We consider two types of structures: either a given Fibonacci sequence or a periodic repetition of a given sequence called Fibonacci superlattice. Various properties of these systems such as: the scaling law and the self-similarity of the transmission spectra or the power law behavior of the measure of the energy spectrum have been highlighted for waves of sagittal polarization in normal and oblique incidence. In addition to the allowed modes which propagate along the system, we study surface modes induced by the surface of the Fibonacci superlattice. In comparison with solid-solid layered structures, the solid-fluid systems exhibit transmission zeros which can break the self-similarity behavior in the transmission spectra for a given sequence or induce additional gaps other than Bragg gaps in a periodic structure.

New coordination features; a bridging pyridine and the forced shortest non-covalent distance between two CO32- species.

The aerobic reaction of the multidentate ligand 2,6-bis-(3-oxo-3-(2-hydroxyphenyl)-propionyl)-pyridine, H4L, with Co(ii) salts in strong basic conditions produces the clusters [Co4(L)2(OH)(py)7]NO3 (1) and [Co8Na4(L)4(OH)2(CO3)2(py)10](BF4)2 (2). Analysis of their structure unveils unusual coordination features including a very rare bridging pyridine ligand or two trapped carbonate anions within one coordination cage, forced to stay at an extremely close distance (dO···O = 1.946 Å). This unprecedented non-bonding proximity represents a meeting point between long covalent interactions and "intermolecular" contacts. These original motifs have been analysed here through DFT calculations, which have yielded interaction energies and the reduced repulsion energy experimented by both CO32- anions when located in close proximity inside the coordination cage.

On the stability of AuFe alloy nanoparticles.

AuFe nanoparticles with mean diameters d p  = 13.2 nm have been prepared by inert-gas condensation. Conventional and high-resolution transmission electron microscopy and energy-dispersive x-ray spectroscopy investigations show that the particles are mostly icosahedra. Scanning transmission electron microscopy-energy-dispersive x-ray spectroscopy and scanning transmission electron microscopy-electron energy-loss spectroscopy show that the as-grown particles exhibit a core-shell structure. The shell is mainly composed of an amorphous FeO layer. Although Fe and Au are immiscible in the bulk, the particle cores are found to be homogeneously mixed at the atomic level with a local composition of around Au84Fe16 (at.%). AuFe nanoparticles exhibit a complex magnetic structure in which the core behaves as a spin glass with a freezing temperature of 35 K, whereas the amorphous FeO shell behaves as a ferro-ferrimagnetic system. On annealing above 300 °C, the AuFe icosahedra phases separate into their elemental constituents. Hence the as-grown AuFe icosahedra are metastable, thereby implying that the bulk phase diagram also applies for nanoscopic materials.

The D-repeat polymorphism in the ASPN gene and primary knee osteoarthritis in a Mexican mestizo population: a case-control study.

BACKGROUND: A genetic association between osteoarthritis (OA) and a polymorphism in the aspartic acid (D) repeat of the asporin (ASPN) gene has been reported in Japanese, Han Chinese, Greek and UK Caucasian populations of patients having knee and hip OA. Such an association has not been previously described among the Mexican mestizo population. The aim of this study was to analyze the association of the ASPN gene D-repeat polymorphism in a Mexican mestizo population with primary knee OA as well as in healthy controls. MATERIALS AND METHODS: A case-control study was conducted on a Mexican mestizo population of northern Mexico. The repeat polymorphism was genotyped in 440 subjects (218 cases and 222 healthy controls). Primary knee OA was diagnosed according to American College of Rheumatology and Kellgren-Lawrence criteria, and allelic association was examined adjusting for other risk variables. RESULTS: After adjusting for some covariates, menopause and the D16 allele showed a trend toward being risk factors for knee OA in a Mexican mestizo population. Also, the D12 allele could be considered as a protective factor. CONCLUSIONS: These findings suggest that polymorphisms within the ASPN gene could influence knee OA susceptibility, but these associations must be confirmed by independent studies in larger samples and different ethnic groups to support the role of the D-repeat polymorphism in the ASPN gene as risk or protection factors for knee OA in a Mexican population.

Hip fracture rates and bisphosphonate consumption in Spain. An ecologic study.

INTRODUCTION: Bisphosphonates are used worldwide to treat osteoporosis and, thus, to prevent fractures. Though they have been proven in clinical trials to avoid some fractures, their effectiveness in reducing hip fractures is unclear. The aim of the present study was to explore the relationship between bisphosphonate use and hip fracture trends in Spain. METHODS: For this purpose, an ecologic study spanning 2002 to 2008 was conducted in Spain. Consumption data were obtained from the Spanish Ministry of Health and Social Policy. The number of hip fractures was obtained from hospital discharges; annual hip fracture rates were determined and standardized using the Spanish 2002 population census. A linear regression was performed between fracture rate and use of bisphosphonates; R(2) and Pearson correlation coefficient were calculated. RESULTS: From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. In the same period, the crude hip fracture rate increased from 2.85 to 3.02 cases per 1,000 inhabitants older than 50 years; however, when age standardized rates were estimated, the rate declined from 2.85 to 2.79. Analyzed by sex, the standardized rate for men slightly increased from 1.45 to 1.48, while for women the rate significantly dropped from 4.00 to 3.91. CONCLUSION: A small effect of bisphosphonates on hip fracture rates can not be ruled out; however, other factors might partially explain this decline. Assuming this medication was the only cause for hip fracture rate reduction, the elevated medication cost to avoid a single hip fracture makes it necessary to explore less expensive interventions.

A genetic determinant of the striatal dopamine response to alcohol in men.

Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.

Adverse events associated with pandemic influenza vaccines: comparison of the results of a follow-up study with those coming from spontaneous reporting.

Prior to marketing of pandemic influenza vaccines, the only safety data were those from clinical trials. The objective of this study was to compare information coming from spontaneous reporting with that systematically collected in a formal observation study; this also permits to further evaluate safety of pandemic influenza vaccines in the targeted patients' population. Out of a sample of 507 vaccinated subjects, 103 (20.3%) developed some complication. In the same period 83 reports corresponding to all vaccinated people of Castilla y León (n=131,462) were collected. Severe cases were 1 (1%) and 7 (8.4%), respectively, with the two procedures. The spontaneous reporting rate was 322-fold lower than that identified through the follow-up study; when considered the severe cases, it was 37-fold lower. Under certain circumstances reporting might be performing better than usual due to strengthening of the surveillance system. Adverse events observed for the pandemic H1N1 vaccines lie within the expected safety profile for common events with influenza vaccines. An overall benefit-risk assessment of these vaccines should be done.

Frequency of specific CD8+ T cells for a promiscuous epitope derived from Trypanosoma cruzi KMP-11 protein in chagasic patients.

The K1 peptide is a CD8(+)T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein. We have previously shown that this peptide induces IFN-gamma secretion by CD8(+)T cells. The aim of this study was to characterize the frequency of K1-specific CD8(+)T cells in chagasic patients. Nineteen HLA-A2(+)individuals were selected from 50 T. cruzi infected patients using flow cytometry and SSP-PCR assays. Twelve HLA-A*0201(+)noninfected donors were included as controls. Peripheral blood mononuclear cells were stained with HLA-A2-K1 tetramer, showing that 15 of 19 infected patients have K1-specific CD8(+)T cells (0.09-0.34% frequency) without differences in disease stages or severity. Of note, five of these responders were A*0205, A*0222, A*0226, A*0259 and A*0287 after molecular typing. Thus, a phenotypic and functional comparison of K1-specific CD8(+)T cells from non-HLA-A*0201 and HLA-A*0201(+)infected patients was performed. The results showed that both non-HLA-A*0201 and HLA-A*0201(+)individuals have a predominant effector memory CD8(+)T cell phenotype (CCR7-, CD62L-). Moreover, CD8(+)T cells from non-HLA-A*0201 and HLA-A*0201(+)individuals expressed IL-2, IFN-gamma and perforin without any differences. These findings support that K1 peptide is a promiscuous epitope presented by HLA-A2 supertype molecules and is highly recognized by chagasic patients.

Dexamethasone treatment in chronic subdural haematoma.

INTRODUCTION: Neurosurgeons are familiar with chronic subdural haematoma (CSH), a well-known clinical entity, which is usually treated by some modality of trepanation. Despite the excellent outcomes obtained by surgery, complications may occur, some of which may be potentially severe or fatal. Furthermore, up to 25% recurrence rate is reported. The authors present a novel approach to the management of CSH based on the use of dexamethasone as the treatment of choice in the majority of cases. PATIENTS AND METHODS: Medical records of 122 CSH patients were retrospectively reviewed. At admission, symptomatic patients were classified according to the Markwalder Grading Score (MGS). Those scoring MGS 1-2 were assigned to the Dexamethasone protocol (4 mg every 8h, re-evaluation after 48-72 h, slow tapering), and those scoring MGS 3-4 were, in general, assigned to the Surgical protocol (single frontal twistdrill drainage to a closed system, without irrigation). Patients were followed in the Outpatient Office with neurological assessment and serial CT scans. RESULTS. Between March 2001 and May 2006, 122 consecutive CSH patients (69% male, median aged of 78, range 25-97) were treated. Seventy-three percent of the patients exhibited some kind of neurological defect (MGS 2-3-4). Asymptomatic patients (MGS 0) were left untreated. Initial treatment assignment was: 101 dexamethasone, 15 subdural drain, 4 craneotomy and 2 untreated. Twenty-two patients on dexamethasone ultimately required surgical drain (21.8%). Favourable outcome (MGS 0-1-2) was obtained in 96% and 93.9% of those treated with dexamethasone and surgical drain, respectively. Median hospital stay was 6 days (range 1- 41) for the dexamethasone group and the whole series, and 8 days (range 5-48) for the surgical group. Overall mortality rate was 0.8% and re-admissions related to the haematoma reached 14.7% (all maintained or improved their MGS). Medical complications occurred in 34 patients (27.8%), mainly mild hyperglycemic impairments. Median outpatient follow up was 25 weeks (range 8-90), and two patients were lost. DISCUSSION: The rationale for the use of dexamethasone in CSH lies in its anti-angiogenic properties over the subdural clot membrane, as it is derived from experimental studies and the very few clinical observations published. Surgical evacuation of CSH is known to achieve excellent results but no well-designed trials compare medical versus surgical therapies. The experience obtained from this series lets us formulate some clinical considerations: dexamethasone is a feasible treatment that positively compares to surgical drain (and avoided two thirds of operations); the natural history of CSH allows a 48-72 h dexamethasone trial without putting the patient at risk of irreversible deterioration; eliminates all morbidity related to surgery and recurrences; does not provoke significant morbidity itself; reduces hospital stay; does not preclude ulterior surgical procedures; it is well tolerated and understood by the patient and relatives and it probably reduces costs. The authors propose a protocol that does not intend to substitute surgery but to offer a safe and effective alternative. CONCLUSION: Data obtained from this large retrospective series suggests that dexamethasone is a feasible and safe option in the management of CSH. In the author's experience dexamethasone was able to cure or improve two thirds of the patients. This fact should be confirmed by others in the future. The true effectiveness of the therapy as compared to surgical treatment could be ideally tested in a prospective randomized trial.