Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE: To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed. RESULTS: Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5-128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0-pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen. CONCLUSIONS: In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.

[Non-aneurysmal subarachnoid haemorrhage secondary to panarteritis nodosa at paediatric age: a case report]. / Hemorragia subaracnoidea no aneurismatica secundaria a panarteritis nodosa en edad pediatrica: caso clinico.

INTRODUCTION: Polyarteritis nodosa is a necrotizing vasculitis that mainly affects small and medium-sized arteries in skin and internal organs. Neurological involvement is reported in around 25% of cases: ischemic stroke is relatively common, but haemorrhagic lesions are extremely rare. Subarachnoid haemorrhage in polyarteritis nodosa is an uncommon expression of this disease, mostly associated with aneurism rupture. To the best of the authors' knowledge, there is just one published case in pediatric age with polyarteritis nodosa and subarachnoid haemorrhage with no underlying aneurismal disease. CASE REPORT: A 7-year-old girl, who presented a non-aneurismal subarachnoid haemorrhage with intraparenchymal extension in the left basal ganglia. She was previously diagnosed with polyarteritis nodosa and prothrombotic condition, being under immunosuppressive and anti-platelet treatment at that moment. CONCLUSIONS: The clinical features of polyarteritis nodosa together with continued anti-platelet therapy to prevent thromboembolic disease in this patient could have predisposed to the haemorrhagic event in the process of cerebral vasculitis. Standard subarachnoid haemorrhage management is initially required in such cases as cerebral aneurysms are the most common cause of haemorrhage in the context of polyarteritis nodosa disease.

TITLE: Hemorragia subaracnoidea no aneurismatica secundaria a panarteritis nodosa en edad pediatrica: caso clinico.Introduccion. La panarteritis nodosa es una vasculitis necrotizante que afecta de manera predominante a arterias de pequeño y mediano calibre de la piel y los organos internos. La afectacion neurologica sucede en un 25% de casos: los ictus isquemicos son relativamente frecuentes, pero las lesiones hemorragicas resultan extremadamente raras. La hemorragia subaracnoidea es una expresion poco comun de la enfermedad, asociada la inmensa mayoria de las veces a patologia aneurismatica. En nuestro conocimiento, solo existe otro caso descrito de panarteritis nodosa con hemorragia subaracnoidea en la edad pediatrica sin patologia aneurismatica subyacente. Caso clinico. Niña de 7 años que presento una hemorragia subaracnoidea no aneurismatica con extension intraparenquimatosa a los ganglios basales izquierdos. Previamente se habia diagnosticado panarteritis nodosa y enfermedad protrombotica, en tratamiento con farmacos inmunodepresores y antiagregantes en ese momento. Conclusiones. Las caracteristicas clinicas de la panarteritis nodosa, junto con el tratamiento antiagregante para prevenir la enfermedad tromboembolica en nuestra paciente, podrian haber predispuesto al evento hemorragico en el proceso de la vasculitis cerebral. El manejo estandar de la hemorragia subaracnoidea es necesario en estos casos debido a que los aneurismas cerebrales son la causa mas comun de hemorragia subaracnoidea en un contexto de panarteritis nodosa.

Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).

OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.

Activity of the novel BCR kinase inhibitor IQS019 in preclinical models of B-cell non-Hodgkin lymphoma.

BACKGROUND: Pharmacological inhibition of B cell receptor (BCR) signaling has recently emerged as an effective approach in a wide range of B lymphoid neoplasms. However, despite promising clinical activity of the first Bruton's kinase (Btk) and spleen tyrosine kinase (Syk) inhibitors, a small fraction of patients tend to develop progressive disease after initial response to these agents. METHODS: We evaluated the antitumor activity of IQS019, a new BCR kinase inhibitor with increased affinity for Btk, Syk, and Lck/Yes novel tyrosine kinase (Lyn), in a set of 34 B lymphoid cell lines and primary cultures, including samples with acquired resistance to the first-in-class Btk inhibitor ibrutinib. Safety and efficacy of the compound were then evaluated in two xenograft mouse models of B cell lymphoma. RESULTS: IQS019 simultaneously engaged a rapid and dose-dependent de-phosphorylation of both constitutive and IgM-activated Syk, Lyn, and Btk, leading to impaired cell proliferation, reduced CXCL12-dependent cell migration, and induction of caspase-dependent apoptosis. Accordingly, B cell lymphoma-bearing mice receiving IQS019 presented a reduced tumor outgrowth characterized by a decreased mitotic index and a lower infiltration of malignant cells in the spleen, in tight correlation with downregulation of phospho-Syk, phospho-Lyn, and phospho-Btk. More interestingly, IQS019 showed improved efficacy in vitro and in vivo when compared to the first-in-class Btk inhibitor ibrutinib, and was active in cells with acquired resistance to this latest. CONCLUSIONS: These results define IQS019 as a potential drug candidate for a variety of B lymphoid neoplasms, including cases with acquired resistance to current BCR-targeting therapies.

In vivo adhesion of malignant B cells to bone marrow microvasculature is regulated by α4ß1 cytoplasmic-binding proteins.

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) cells must attach to the bone marrow (BM) microvasculature before lodging in the BM microenvironment. Using intravital microscopy (IVM) of the BM calvariae we demonstrate that the α4ß1 integrin is required for MM and CLL cell firm arrest onto the BM microvasculature, while endothelial P-selectin and E-selectin mediate cell rolling. Talin, kindlin-3 and ICAP-1 are ß1-integrin-binding partners that regulate ß1-mediated cell adhesion. We show that talin and kindlin-3 cooperatively stimulate high affinity and strength of α4ß1-dependent MM and CLL cell attachment, whereas ICAP-1 negatively regulates this adhesion. A functional connection between talin/kindlin-3 and Rac1 was found to be required for MM cell attachment mediated by α4ß1. Importantly, IVM analyses with talin- and kindlin-3-silenced MM cells indicate that these proteins are needed for cell arrest on the BM microvasculature. Instead, MM cell arrest is repressed by ICAP-1. Moreover, MM cells silenced for talin and kindlin-3, and cultured on α4ß1 ligands showed higher susceptibility to bortezomib-mediated cell apoptosis. Our results highlight the requirement of α4ß1 and selectins for the in vivo attachment of MM and CLL cells to the BM microvasculature, and indicate that talin, kindlin-3 and ICAP-1 differentially control physiological adhesion by regulating α4ß1 activity.

An artificial neural network model for predicting the subcellular localization of photosensitisers for photodynamic therapy of solid tumours.

Photodynamic therapy (PDT) is a promising modality for the treatment of tumours based on the combined action of a photosensitiser (PS), visible light and molecular oxygen, which generates a local oxidative damage that leads to cell death. The site where the primary photodynamic effect takes place depends on the subcellular localization of the PS and affects the mode of action and efficacy of PDT. It is therefore of prime interest to develop structure-subcellular localization prediction models for a PS from its molecular structure and physicochemical properties. Here we describe such a prediction method for the localization of macrocyclic PSs into cell organelles based on a wide set of physicochemical properties and processed through an artificial neural network (ANN). 128 2D-molecular descriptors related to lipophilicity/hydrophilicity, charge and structural features were calculated, then reduced to 76 by using Pearson's correlation coefficient, and finally to 5 using Guyon and Elisseeff's algorithm. The localization of 61 PSs was compiled from literature and distributed into 3 possible cell structures (mitochondria, lysosomes and "other organelles"). A non-linear ANN algorithm was used to process the information as a decision tree in order to solve PS-organelle assignment: first to identify PSs with mitochondrial and/or lysosomal localization from the rest, and to classify them in a second stage. This sequential ANN classification method has permitted to distinguish PSs located into two of the most important cell targets: lysosomes and mitochondria. The absence of false negatives in this assignation, combined with the rate of success in predicting PS localization in these organelles, permits the use of this ANN method to perform virtual screenings of drug candidates for PDT.

[Abducens nerve palsy due to postraumatic retroclival and spinal subdural hematoma: case report and literature review]. / Paresia VI par craneal por hematoma subdural retroclival y espinal postraumatico: presentacin de un caso y revision de la literatura.

INTRODUCTION: Retroclival posttraumatic hematomas are extremely rare and almost exclusive to childhood. Only one case of retroclival subdural hematoma has been reported in the literature to date. CASE REPORT: An 8-year-old boy suffered a severe head injury with cervical hyperextension as the result of a bicycle accident. On admission his initial Glasgow Coma Score was 13 and he had diplopia due to right palsy of the VI nerve. A retroclival subdural hematoma was observed by CT and MRI of the craneovertebral junction. Management was conservative and a rigid collar was placed. Palsy of VI nerve recovered spontaneously at 6 days and at discharge the patient had only cervical pain. Follow up at 3 months after the accident showed clinical and radiological resolution. CONCLUSION: Traumatic retroclival hematomas are mainly a pediatric entity due to immaturity of the cranio-cervical junction. Treatment consists of placement of a rigid collar although clinical progression may require surgical evacuation.

[Sinking skin flap syndrome]. / Sindrome del colgajo hundido.

INTRODUCTION: The sinking skin flap syndrome is a complication of decompressive craniectomies. It is of relevance not only due to its frequency, it is often underdiagnosed, but also because of the possibility of reversing the symptoms with the proper treatment. CASE REPORT: A 53-year-old female sustained a severe head injury. The initial Glasgow Coma Scale was 6T. The CT scan showed a severe traumatic injury in the left temporal lobe that required a decompressive craniectomy. After surgery the patient developed aphasia and right hemiparesis but progressively improved. Four months after surgery, however, she presented neurological worsening. An MRI showed skin retraction with a mass effect on the brain parenchyma at the craniectomy defect. A cranioplasty was performed and the patient progressively recovered neurologically. CONCLUSIONS: The symptoms of sinking skin flap are headache, dizziness, inappropriate behaviour, neurological functional impairment and/or seizures. The symptoms worsen with the Valsalva manoeuvres and with changes in position. Typically, symptoms 3 to 5 months to appear. Theories to explain these symptoms include a direct atmospheric pressure effect, brain blood flow changes, alteration in cerebrospinal fluid dynamics and metabolic disturbances. Diagnosis is performed through clinical observation but imaging studies are recommended to confirm the diagnosis. The treatment of choice is a cranioplasty. Prognosis is excellent and almost all patients recover completely.

Comparative study of neural networks and least mean square algorithm applied to the optimization of cosmetic formulations.

In this work, a comparative study between two methods to acquire relevant information about a cosmetic formulation has been carried out. A Design of Experiments (DOE) has been applied in two stages to a capillary cosmetic cream: first, a Plackett-Burman (PB) design has been used to reduce the number of variables to be studied; second, a complete factorial design has been implemented. With the experimental data collected from the DOE, a Least Mean Square (LMS) algorithm and Artificial Neural Networks (ANN) have been utilized to obtain an equation (or model) that could explain cream viscosity. Calculations have shown that ANN are the best prediction method to fit a model to experimental data, within the interval of concentrations defined by the whole set of experiments.

[The effectiveness of gravitational valves in the prevention of over-drainage in adult patients with hydrocephalus]. / Efectividad de las válvulas gravitacionales en la prevención del hiperdrenaje en pacientes adultos con hidrocefalia.

AIM: To evaluate the effect of gravitational valves on over-drainage in hydrocephalus in adults. PATIENTS AND METHODS: We performed a retrospective study of the shunt systems placed in patients over the age of 18 years between 1998 and 2006. Patients were divided into two groups: non-GV group (without gravitational valve) and GV group (with a gravitational valve, Aesculap-Miethke 5/35). The complications that occurred during the first year following the placement of the shunt system were recorded. RESULTS: Of a total of 137 patients, 91 were from the non-GV group and 46 belonged to the GV group. Mean age: non-GV group, 62.1 years; and GV group, 64.2 years, without any significant differences. In 80 patients the aetiology was chronic adult hydrocephalus, 19 were due to expansive processes, 15 due to vascular causes, eight pseudo tumours, six post-traumatic injuries and nine were due to other causes. In the non-GV group, 9.89% presented over-drainage, whereas there were no cases in the GV group; the difference was statistically significant (p = 0.029). In the rest of the complications there were no significant differences between the two groups. The total complications in the non-GV group were 25.27% and in the GV group, 6.52%, and there were significant differences (p = 0.01), although, above all, at the expense of over-drainage, because if this complication was excluded, then the differences were no longer significant (p = 0.175). CONCLUSIONS: In our series, the use of gravitational valves in the prevention of over-drainage in adult hydrocephalus proved to be more effective than employing valves without the gravitational device.

[Post-transplant diabetes mellitus depending on the pre-transplant dialysis technique]. / Diabetes mellitus post-trasplante según técnica de diálisis previa al trasplante.

Post-transplant diabetes mellitus (PTDM) is one of the most important complications in kidney transplant patients because it has a significant impact on graft and patient survival. Diagnosis of PTDM should be based on the American Diabetic Association criteria. Recent studies show the value of performing an oral glucose tolerance test in all patients. Multiple risk factors promote PTDM. PTDM incidence may be reduced by controlling modifiable factors (immunosuppression, obesity, infections...). According to RMRC data, patients on peritoneal dialysis are younger, but have a greater incidence rate of dyslipidemia and obesity. Recent data suggest that subclinical information, adiponectin, and ghrelin may be a significant pathogenetic factor in development of insulin resistance and diabetes mellitus. There is no clear evidence that the dialysis procedure influences the subclinical inflammatory state and adipocytokines. According to data from the Spanish group for the study of PTDM, a relationship exists between ghrelin levels and sex in patients on peritoneal dialysis. The most common metabolic complication in patients on peritoneal dialysis is hyperglycemia. Pre-transplant hyperglycemia promotes the occurrence of PTDM. There is no clear evidence in the literature showing that the dialysis procedure is a risk factor for the occurrence of PTDM. Additional multicenter studies are required to analyze the clinical and biological characteristics of renal patients and their relationship to PTDM.

[The microbial pattern of the catheter exit-site infection in peritoneal dialysis: A non-diphtheria Corynebacteria emergence?]. / Patrón microbiológico de la infección del cateter peritoneal: aumento de Corynebacterium sp?

BACKGROUND: A prospective cohort study was undertaken to compare the rates of the infecting microorganisms of the peritoneal catheter exit-site in three periods of the prophylactic protocol of a peritoneal dialysis program. All patients treated for more than one month on Peritoneal Dialysis were included: Fourty-eight in Period 1 (P1), 48 in Period 2 (P2), and 54 in Period 3 (P3). Each period was of 3 years. METHODS: Infection prophylaxis protocol: P1: hydrogen peroxide or povidone iodine and non-occlusive dressing; P2: sterile water (boiled water) instead of antiseptic agents, semi-permeable dressing for taking showers, and nasal mupirocine prophylaxis for Staphylococcus aureus carriers; P3: equal to P2, plus local application of antibiotics in equivocal exit-site for infection and argentic nitrate in granulation tissue. MAIN OUTCOME MEASURE: The rates of catheter infection and microorganisms causing infection were analysed by means of the Poisson regression method. Chi-square and ANOVA when appropriate. RESULTS: The proportion of catheters implanted by nephrologist or surgeon (p<0.01) and modality treatment by CAPD or CCPD (p<0.0001) were significantly different in the three periods, while the Staph. Aureus carrieres was in the limit of significance (p=0.048). Throughout the three periods, a significantly decreasing rate of total (P=0.0035) and acute infections (P<0.001), Staph. aureus (P=0.003) and peritonitis (P=0.0025) were found. The Pseudomonas aer. (P=0.006) and Gram negative Bacteria (P=0.023) decreased significantly in P2. The multiple factor analysis included eight factors: sex, age group, ESRD, DM, catheter implantation (nephrologist, surgeon), modality treatment (CAPD, CCPD), manufacturer and prophylaxis period as possible predictors of the catheter infections, the specific microorganisms and the peritonitis. That analysis revealed the prophylaxis period as the main predictive factor of the improvements found (p<0.02,- p<0.001). In contrast, the Corynebacteria spp. increased significantly (P=0.008) throughout the three periods. One half of the Corynebacteria in each period could be considered colonisers. The other half caused true infections, but not one of those episodes required catheter intervention. The non-diphtheria Corynebacteria increase was found related with the continuous cycling Peritoneal Dialysis treatment in multiple factor analysis (p=0.0023) and in the proportion analysis (P=0.039, c2). CONCLUSION: The progressive protocol applied obtained good results, without the continued use of local antiseptics or antibiotics at the exit-site. However, the non-diphtheria Corynebacteria sp. infection increment favours the consideration of an antiseptic agent for the exit-site care.

Porphycenes: facts and prospects in photodynamic therapy of cancer.

The photodynamic process induces cell damage and death by the combined effect of a photosensitizer (PS), visible light, and molecular oxygen, which generate singlet oxygen ((1)O(2)) and other reactive oxygen species that are responsible for cytotoxicity. The most important application of this process with increasing biomedical interest is the photodynamic therapy (PDT) of cancer. In addition to hematoporphyrin-based drugs, 2nd generation PSs with better photochemical properties are now studied using cell cultures, experimental tumors and clinical trials. Porphycene is a structural isomer of porphyrin and constitutes an interesting new class of PS. Porphycene derivatives show higher absorption than porphyrins in the red spectral region (lambda > 600 nm, epsilon > 50000 M-(1)cm(-1)) owing to the lower molecular symmetry. Photophysical and photobiological properties of porphycenes make them excellent candidates as PSs, showing fast uptake and diverse subcellular localizations (mainly membranous organelles). Several tetraalkylporphycenes and the tetraphenyl derivative (TPPo) induce photodamage and cell death in vitro. Photodynamic treatments of cultured tumor cells with TPPo and its palladium(II) complex induce cytoskeletal changes, mitotic blockage, and dose-dependent apoptotic or necrotic cell death. Some pharmacokinetic and phototherapeutic studies on experimental tumors after intravenous or topical application of lipophilic alkyl-substituted porphycene derivatives are known. Taking into account all these features, porphycene PSs should be very useful for PDT of cancer and other biomedical applications.

[A burden questionnaire for caregivers of peritoneal dialysis patients]. / Cuestionario de sobrecarga de cuidadores de pacientes de diálisis peritoneal.

INTRODUCTION: Despite the interest generated by the increasing number of studies that measure Quality of Life among patients and caregivers, few of these studies measure the caregivers burden in Peritoneal Dialysis (PD). OBJECTIVE: The main target of this study was to create a burden measure questionnaire applicable amongst caregivers of PD patients. INCLUSION CRITERIA: 1) Patients had to be in PD treatment for more than 3 months; 2) Patients had to receive help with the PD treatment from a caregiver. The study was divided into 3 phases: 1st) design and use of the initial questionnaire; 2nd) a test-retest on a modified scale; and 3rd) to provide the questionnaire-3 to two collaborative centres with similar PD programs. Four groups of caregivers were established: A1:23, A2:17, B:7 and C:16 caregivers. We applied 5 scales (5): 1--Patient Dependence on caregiver, from caregivers' view (D); 2--Complete caregiver burden (CB), including 12 items which measure the caregivers' subjective burden, 3--Reduced caregiver burden (RB), as the one before but with only 8 items, 4--Repercussions on the caregiver (R), which measures objective burden; 5--Specific PD tasks (ST), a scale that measures the effort the tasks implied in the PD treatment represent for the caregiver. RESULTS: We studied 63 caregivers (table I): mean age: 53.43 (SD = 12.3); Sex: Females: 86.4%, Males: 13.6%, corresponding to 63 patients: mean age: 59.79 (SD = 15.9); Sex: Males: 80.3%, Females: 19.7%. Valuable results for reliability, unidimensionality, and discrimination were obtained in the 1st and 2nd phases, except for burden scale which was compound of two factors; then one of those factors was suppressed. In the 3rd phase, ANOVA did not show any differences between centres (table II). Consequently, all caregivers could be analysed together. Reliability results for each one of the third phase scales (table III) were: D: Cronbach alpha = 0,886; CB: alpha = 0,894; RB: alpha = 0,857; R: alpha = 0,892; ST: alpha = 0,62. Although the ST scale obtained an acceptable reliability, it was suppressed in the 3rd phase due to the low correlation with other scales and the fact that it was not applicable to all caregivers. Finally, a direct correlation was found between third phase scales (table IV): D-RB: r = 0.502, p < or = 0.001; D-R: r = 0.599, p < or = 0.001; RB-R: r = 0.775, p < or = 0.001. We must headlight that both Burden scales, and the Repercussion scale, obtained a direct correlation with the Dependency scale. CONCLUSION: A questionnaire has been created to measure burden and repercussions on caregivers of peritoneal dialysis patients. It can already be applied, as requirements of both reliability and validity are fulfilled. This questionnaire can be a useful tool to prevent caregivers' burnout.

Recent advances in combinatorial chemistry applied to development of anti-HIV drugs.

A compilation of combinatorial chemistry techniques applied to anti-HIV drug development is presented in this review. This synthetic strategy together with high throughput screening assays has allowed the discovery and optimization of novel lead anti-HIV compounds.

Bovine tuberculosis in wild boar (Sus scrofa), red deer (Cervus elaphus) and cattle (Bos taurus) in a Mediterranean ecosystem (1992-2004).

During the last 12 years, an increasing frequency in condemnation of hunted red deer and wild boar carcasses due to the presence of tubercle-like lesions has been observed in Extremadura (Western Spain). Before 1993, tuberculosis was a very rare finding in hunted animals. The current tuberculosis regional prevalence in cattle approaches 0.4% after years of expensive test and slaughter campaigns. It is imperative to investigate the epidemiology of Mycobacterium bovis infection in red deer and wild boar in order to keep a good health status and to maintain the effectiveness of domestic species TB eradication programs. The present paper evaluates the problem in Sierra de San Pedro, estimating the prevalence of TB in wild boar and red deer, the main wild artiodactyls in the area, and domestic cattle since 1992-2004, by the use of a low-cost surveillance method based on detailed pathological inspection of hunted animal carcasses. Microbiology and molecular epidemiology studies on several M. bovis isolates from domestic and wild animals helped to define the interspecies contacts. These findings, as well as recent history of game estates management and descriptive epidemiology field work, throw light on the rise and maintenance of these epizootics.