[Early source control of infection in patients seen in the emergency department: a systematic review]. / Control precoz del foco de infección en los pacientes atendidos en el servicio de urgencias: una revisión sistemática.

OBJECTIVE: The term source (or focus) control encompasses all those physical measures that can be used to reduce the inoculum and modify those factors in the infectious medium that promote microbial growth or foreign antimicrobial defenses of the host. The main objective of this systematic review (SR) is to know and compare whether early detection and control of the focus (in less than 6 hours) in adult patients treated in the ED for severe infection or sepsis, compared to not controlling the focus or delayed focus control (more than 12 hours) is more effective and safer (improves clinical evolution, mortality, complications, hospital stay or need for ICU admission). METHODS: A systematic review is carried out following the PRISMA regulations in the databases of PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase and ClinicalTrials.gov from January 2000 to December 31, 2023 without language restrictions and using a combination of MESH terms: "Source Control", "Early" "Infection OR Bacterial Infection OR Sepsis", "Emergencies OR Emergency OR Emergency Department" and "Adults". Observational cohort studies were included. No meta-analysis techniques were performed, but results were compared narratively. RESULTS: A total of 1,658 articles were identified, of which 2 that met the inclusion criteria and were classified as high quality were finally analyzed. The included studies represent a total of 2,404 patients with 678 cases in which an intervention was performed to control the focus (28.20%). In the first study, 28-day mortality was lower in patients who underwent an intervention to control the focus (12.3% vs. 22.5%; P <0.001), with an adjusted HR of 0.538 (95% CI: 0.389-0.744; P<0.001). In the second, it was demonstrated that the time elapsed from when the patient was evaluated for the first time and was hemodynamically stabilized, until the start of surgery was associated with his survival at 60 days with an OR of 0.31 (95% CI: 0.19-0.45; P <0.0001). In fact, for each hour of delay an adjusted OR of 0.29 (95% CI: 0.16-0.47; P<0.0001) is established. So if the intervention is performed before 2 hours at 60 days, 98% of the patients are still alive, if it is performed between 2-4 hours it is reduced to 78%, if it is between 4-6 hours it drops to 55%, but if it is done for more than 6 hours there will be no survivors at 60 days. CONCLUSIONS: This review shows that source control carried out after the evaluation of patients attending the ED reduces short-term mortality (30-60 days) and that it would be advisable to implement any required source control intervention as soon as possible, ideally early (within 6 hours).

Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

Cognitive outcomes following functional neurosurgery in refractory OCD patients: a systematic review.

Neurosurgery is a therapeutic option for patients with refractory obsessive-compulsive disorder who do not respond to previous treatments. Although its efficacy in reducing clinical symptomatology has been proven, few studies have analyzed its effects at the cognitive level. The aim of this systematic review was to describe the cognitive outcomes of functional neurosurgery in patients that went through capsulotomies or cingulotomies. PubMed, Medline, Scopus, PsycInfo, PsyArticles, and Web of Knowledge were searched for studies reporting cognitive outcomes in refractory obsessive-compulsive patients after capsulotomies and cingulotomies. The risk of bias was assessed with the Assessment Tool for Before-After (Pre-Post) Studies With No Control Group tool; 13 studies met inclusion criteria, including 205 refractory obsessive-compulsive disorder patients for both surgical procedures. Results showed a substantial number of studies that did report significant cognitive improvement after surgery, being this improvement specially related to memory and executive functions. The second-most frequent finding is the maintenance of cognitive performance (nor improvement or worsening). From a neuropsychological point of view, this outcome might be considered a success, given that it is accompanied by amelioration of obsessive-compulsive symptoms. Subtle cognitive adverse effects have also been reported. Neurosurgery procedures appear to be safe from a cognitive point of view. Methodological issues must be improved to draw clearer conclusions, but capsulotomies and cingulotomies constitute an effective alternative treatment for refractory obsessive-compulsive disorder patients.

Development of an immune-nutritional prognostic index in patients with muscle-infiltrating bladder cancer candidates for radical cystectomy.

INTRODUCTION: Muscle-infiltrating bladder tumor (MIBT) has a recurrence-free survival (RFS) of 50% at 5 years. Although neoadjuvant chemotherapy (NCT) has increased it by 8%, which group of patients benefits the most from this treatment remains unclear. OBJECTIVE: Evaluate the prognostic value of immune-nutritional status in patients with MIBT who are candidates for cystectomy, and to develop a score that allows identifying patients with a worse prognosis (pT3-4 and/or pN0-1). MATERIAL AND METHODS: A retrospective analysis was carried out on 284 patients with MIBT treated with radical cystectomy. Preoperative laboratory tests were analyzed and immune-nutritional indices were calculated. The Kaplan-Meier method was used to calculate the PFS. Cox regression was used for multivariate analysis. RESULTS: Univariate analysis showed a statistically significant relationship with leukocyte/lymphocyte index (p = 0.0001), neutrophil/lymphocyte index (p = 0.02), prognostic nutritional index (p = 0.002), and platelet/lymphocyte ratio (p = 0.002). In multivariate analysis, the leukocyte/lymphocyte ratio (p = 0.002) and PNI (p = 0.04) behaved as independent prognostic factors of decreased RFS. Based on these, a prognostic score was developed to classify patients into 3 prognostic groups. Eighty percent of patients with pT3-4 and/or pN0-1 tumors were in the intermediate-poor prognostic groups. CONCLUSION: The implementation of a precystectomy immune-nutritional score in clinical practice would help in the selection of a group of patients with a more unfavorable pathologic stage and worse PFS. We believe that these patients could benefit more from a NACT.

[Cognitive impairment in the elderly patient with symptomatic severe aortic stenosis. Therapeutic decisions and impact on one-year mortality]. / Deterioro cognitivo en el paciente mayor con estenosis aórtica grave sintomática. Toma de decisiones terapéuticas e impacto sobre la mortalidad al año.

INTRODUCTION: Interventional treatment of severe aortic stenosis includes valve replacement by surgery or transcatheter - transcatheter aortic valve implantation (TAVI). In order to make an adequate selection and to rule out patients with little/no therapeutic benefit, it is recommended to assess comorbidities, frailty and cognitive impairment. AIMS: a) To determine the prevalence of cognitive impairment in older patients with severe aortic stenosis; b) to analyse its influence on decision-making (surgery, TAVI or conservative treatment); and c) to analyse its impact on mortality at one year. MATERIAL AND METHODS: Prospective, longitudinal epidemiological study of patients aged 75 years and older with severe aortic stenosis treated by the Heart-Team. VARIABLES: sociodemographic, clinical, cardiological, functional and mental variables; cognitive impairment assessed by applying the Mini-Mental State Examination (MMSE). RESULTS: We included 300 patients in the study (83.99 ± 4.02 years old; 61.2%, women). Prevalence of cognitive impairment of 15.3%, which was associated with albumin level - odds ratio (OR): 0.082; p = 0.011 - and Barthel (OR: 0.962; p = 0.02) and Lawton (OR: 0.787; p = 0.025) index scores. Surgery was chosen in 24.7% of cases; TAVI in 63.3%; and conservative treatment in 12%. This decision was associated with the score on the Barthel (OR: 0.93; p = 0.012) and Lawton indices (OR: 0.678; p = 0.014), the Short Physical Performance Battery (OR: 0.75; p = 0.037) and the MMSE (OR: 0.691; p < 0.001). Mortality at one year was 14%, and higher in patients with MMSE scores <24 (23.5% vs. 12.8%; p = 0.094). CONCLUSIONS: Cognitive impairment is a very common geriatric syndrome in older patients with severe aortic stenosis that is associated with functional disability in activities of daily living. Cognitive impairment has a high impact on decision-making and appears to be a variable associated with increased mortality.

TITLE: Deterioro cognitivo en el paciente mayor con estenosis aórtica grave sintomática. Toma de decisiones terapéuticas e impacto sobre la mortalidad al año.Introducción. El tratamiento intervencionista de la estenosis aórtica grave incluye el recambio valvular mediante cirugía o vía transcatéter ­implante transcatéter de la válvula aórtica (TAVI)­. Para realizar una adecuada selección y descartar pacientes con escaso/nulo beneficio terapéutico, se recomienda evaluar las comorbilidades, la fragilidad y el deterioro cognitivo. Objetivos. a) Determinar la prevalencia de deterioro cognitivo en pacientes mayores con estenosis aórtica grave; b) analizar su influencia en la toma de decisiones (cirugía, TAVI o tratamiento conservador), y c) analizar su impacto sobre la mortalidad al año. Material y métodos. Estudio epidemiológico longitudinal y prospectivo sobre pacientes de 75 años o más con estenosis aórtica grave atendidos por el Heart-Team. Variables: sociodemográficas, clínicas, cardiológicas, funcionales y mentales; deterioro cognitivo evaluado aplicando el Minimental State Examination (MMSE). Resultados. Incluimos a 300 pacientes en el estudio (83,99 ± 4,02 años; 61,2%, mujeres). Prevalencia de deterioro cognitivo del 15,3%, que se asoció con el nivel de albúmina ­odds ratio (OR): 0,082; p = 0,011­ y las puntuaciones en los índices de Barthel (OR: 0,962; p = 0,02) y Lawton (OR: 0,787; p = 0,025). En el 24,7% de los casos se decidió cirugía; en el 63,3%, TAVI; y en el 12%, tratamiento conservador. Esta decisión se asoció con la puntuación en los índices de Barthel (OR: 0,93; p = 0,012) y Lawton (OR: 0,678; p = 0,014), la Short Physical Performance Battery (OR: 0,75; p = 0,037) y el MMSE (OR: 0,691; p menor de 0,001). La mortalidad al año fue del 14%, superior en los pacientes con puntuaciones en el MMSE menor de 24 (23,5% frente a 12,8%; p = 0,094). Conclusiones. El deterioro cognitivo es un síndrome geriátrico muy frecuente en pacientes mayores con estenosis aórtica grave que se asocia con incapacidad funcional en las actividades de la vida diaria. El deterioro cognitivo tiene un elevado impacto en la toma de decisiones y parece presentarse como una variable asociada a mayor mortalidad.

Gamma Knife® stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience.

INTRODUCTION: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

Multivisceral Transplant in a Patient With Portopulmonary Hypertension: A Case Report.

Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was <30 mm Hg with a pulmonary vascular resistance of <300 dynes.s/cm5 on oral sildenafil and intravenous epoprostenol. Intraoperatively, management required comprehensive transfusion protocols, a careful balance between correcting blood loss and preventing thrombosis. Intravenous epoprostenol, sildenafil, milrinone, and inhaled nitric oxide were used to reduce elevated mean pulmonary artery pressure and right ventricular strain associated with vascular clamping, reperfusion, and massive fluid shifts. Nitric oxide and epoprostenol use unleashed antiplatelet effects on a patient already susceptible to coagulopathy. A multimodal and multidisciplinary approach continued throughout the surgery and in the postoperative period, which led to a successful outcome.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: experience at an epilepsy centre.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Laparoscopic nephron sparing surgery and radical nephrectomy in cT1 renal tumors. Comparative analysis of complications and survival.

INTRODUCTION AND OBJECTIVES: Comparative analysis of postoperative complications and survival between laparoscopic partial nephrectomy (PN) and radical nephrectomy (RN) in cT1 renal cell carcinoma (RCC). MATERIAL AND METHOD: Retrospective study of patients with two kidneys and single renal tumor cT1 treated in our center between 2005 and 2018 by laparoscopic PN or RN. RESULTS: 372 patients met the inclusion criteria for the study. RN was performed in 156 (41.9%) patients and PN in 216 (58.1%). Clavien Dindo III-V complications were observed in 10 (4,6%) PN and 6 (3,9%) RN patients (p = 0.75). The comorbidity Charlson index (CCI) was identified as an independent predictor variable of complications (p = 0.02) and surgical approach did not affect multivariate analysis. Estimated overall survival (OS) was 81.2% and 56.8% at 5 and 10 years in the RN group and 90.2% and 75.7% in the PN group, respectively (p = 0.0001). Obesity (HR 2.77, p = 0.01), CCI ≥ 3 (HR 3.69, p = 0.001) and glomerular filtration rate (GFR) <60 mL/min/1.73 m2 at discharge (HR 1.87, p = 0.03) were identified as predictors of overall mortality. Nephrectomy approach showed no influence on OS. Estimated recurrence-free survival (RFS) was 86.1% at 5 and 10 years in the RN group and 93.5% and 83.6% in the PN group, respectively (p = 0.22). CONCLUSIONS: Laparoscopic PN is not inferior to RN in terms of oncologic and surgical safety in cT1 RCC. Nephrectomy approach did not influence patient OS, however, obesity, CCI ≥ 3 and GFR <60 mL/min/1.73 m2 at discharge did behave as predictors.

Bocio multinodular ectópico submandibular: a propósito de un caso y revisión de la literatura / Submandibular ectopic multinodular goiter: case report and literature review

Resumen El tiroides ectópico es una alteración congénita infrecuente que presenta una prevalencia entre 1/100.000-1/300.000. En el 90% de los casos se encuentra en la línea media cervical, siendo los casos de tiroides ectópico cervical lateral muy infrecuentes. Presentamos el caso de una paciente de 44 años que consultó por presentar una tumoración submandibular izquierda de más de seis meses de evolución. Las pruebas de imagen (ecografía, tomografía computarizada y gammagrafía) sugirieron un bocio ectópico multinodular; la punción aspiración con aguja fina (PAAF) informó de tejido tiroideo sin atipias (Bethesda II) y el estudio sanguíneo de hormonas tiroideas fue normal, orientando finalmente el caso como un bocio multinodular ectópico submandibular eutiroideo. Ante la ausencia de síntomas y signos sugerentes de malignidad, en conjunto con una PAAF con características de benignidad, se decidió realizar seguimiento. En el momento que presentó clínica por efecto masa se decidió realizar la exéresis de la lesión, que confirmó el diagnóstico de bocio multinodular ectópico. Los casos descritos en la literatura de bocio multinodular ectópico submandibular como único tejido tiroideo funcionante son excepcionales. El tiroides ectópico se debe considerar en el diagnóstico diferencial de una masa submandibular. Aunque actualmente no existe un consenso en relación con el manejo de dicha patología, el crecimiento de la masa puede contribuir a la decisión de una exéresis completa del tiroides ectópico, aun tratándose del único tejido tiroideo funcionante.

Abstract Ectopic thyroid is an uncommon congenital disorder with a prevalence between 1/100,000-1/300,000. In 90% of cases, it is placed in cervical midline, being the cases of lateral cervical ectopic thyroid very infrequent. We present the case of a 44-year-old female patient who had a left submandibular mass during more than six months. Imaging tests (ultrasound, computed tomography and scintigraphy) suggested a multinodular ectopic goiter; fine needle aspiration (FNA) reported thyroid tissue without atypia (Bethesda II) and the thyroid hormone blood tests were normal, finally orienting the case as a euthyroid submandibular ectopic multinodular goiter. In the absence of symptoms and signs suggestive of malignancy, together with an FNA with benign characteristics, it was decided to follow up. When the patient presented clinical symptoms due to mass effect, it was decided to perform excision of the lesion, which confirmed the diagnosis of ectopic multinodular goiter. There are very few cases described in the literature of submandibular ectopic multinodular goiter as the only functioning thyroid tissue. Ectopic thyroid should be considered in the differential diagnosis of a submandibular mass. Although there is currently no consensus on the management of this pathology, the growth of the mass may contribute to the decision of a complete excision of the ectopic thyroid, even if it is the only functioning thyroid tissue.

Surgical management of horseshoe kidney tumors. Literature review and analysis of two cases.

INTRODUCTION: The horseshoe kidney is a rare congenital anomaly in the general population that combines renal ectopia, malrotation and abnormal vascular supply. The most frequently developed tumor in this case is renal cell carcinoma (50%). One of its main characteristics is great anatomical variation, especially in terms of vascular structures. MATERIAL AND METHODS: We present two cases of patients with diagnosis of renal tumor in horseshoe kidneys, both treated with laparoscopic partial nephrectomy in our department. Additionally, we have carried a review of the current literature. DISCUSSION: Indications for surgical treatment in this pathology are the same as in kidneys with normal anatomy. Traditionally, treatment has been open surgery, with heminephrectomy as surgery of choice. The current trend is to advocate nephron-sparing surgery, and the laparoscopic approach has been progressively gaining importance. CONCLUSION: A thorough imaging study is essential for proper surgical planning.

Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis.

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04-1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.

Multidisciplinary consensus on optimising the detection of NTRK gene alterations in tumours.

The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionised the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children; and they are either rare tumours with common NTRK fusions that may be diagnostic, or more prevalent tumours with rare NTRK fusions. To assess currently available evidence on this matter, three key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathological Anatomy (SEAP), and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical, and therapeutic aspects of NTRK-fusion tumours. This document also discusses the challenges related to the routine detection of these genetic alterations in a mostly public Health Care System.

SEOM Clinical Guideline of management of soft-tissue sarcoma (2020).

Soft-tissue sarcomas constitute an uncommon and heterogeneous group of tumors of mesenchymal origin. Diagnosis, treatment, and management should be performed by an expert multidisciplinary team. MRI/CT of the primary tumor and biopsy is mandatory before any treatment. Wide surgical resection with tumor-free tissue margin is the mainstay for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not suitable for re-excision. Perioperative chemotherapy should be discussed for high-risk sarcomas of the extremities and trunk-wall. In the case of oligometastatic disease, patients should be considered for local therapies. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. Other drugs have shown activity in second-line therapy and in specific histological subtypes but options are limited and thus, a clinical trial should always be discussed.

Gamma Knife® stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience. / Radiocirugía estereotáctica con Gamma Knife® como tratamiento del temblor esencial y parkinsoniano: experiencia a largo plazo.

INTRODUCTION: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

Healthcare-associated pneumonia: a prospective study in Spain.

OBJECTIVE: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). METHODS: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. RESULTS: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. CONCLUSIONS: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.

Orbital metastases from breast cancer: A retrospective analysis of 28 cases.

Breast cancer account about half of the cases of orbital malignancies due to metastasis. The prognosis is adverse, with average survival from 2 to 34 months. OBJECTIVE: To analyze the clinical and pathological characteristics and outcomes of patients with orbital metastasis from breast cancer. MATERIAL AND METHODS: A retrospective, cross-sectional study of 28 patients seen in the Oncology Hospital of the National Medical Center XXI Century, from February 2003 to February 2019. RESULTS: Of the 28 patients, the median age was 50.8 years. The average time from the diagnosis of breast cancer to the development of orbital metastases was 64 months. 42.8% of the patients were stage IV of onset. The lobular vs ductal ratio was 5.2:1. 92.8% of the cases had luminal profile (one case with overexpression of HER-2), while only one case was triple negative. The most frequent symptoms were: decrease in visual acuity (64.2%), pain (57.1%), amaurosis (28.5%), alterations in mobility (28.5%) and edema (21.4%). Bilateral activity was presented in 25%. A third of the patients received local treatment (radiotherapy, surgery, anti-VEGFR). Overall survival was 67.5 months (1-184 months); however, the overall survival from the diagnosis of orbital metastasis was 26.4 months (1-98 months), with an average progression-free survival of 13.7 months (1-48 months). CONCLUSION: Ophthalmologic evaluation should be performed on all patients with breast cancer and ocular symptoms. Early local treatment should be offered in order to prevent severe complications and reduce the negative impact on quality of life.

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.

Early resynchronization of non-pregnant beef cows based in corpus luteum blood flow evaluation 21 days after Timed-AI.

The study aimed to verify whether a hormone protocol started at Day 13 (D13) after Timed Artificial Insemination (TAI) influences the conception rate. Nelore cows (primiparous and multiparous) from two commercial beef farms (n = 1,431) were first TAI (D0). Timed AI was performed in lots (TAI Lots) ranging from 187 to 346 cows. On D13, regarding the TAI lot, cows were assigned for either receiving (Resynch group, n = 1,002) or not (Control group, a subset of approximately 30%, n = 429) another hormone protocol for resynchronization. The same hormone protocol was used for the first TAI and for the resynchronization, except for 1 mg instead of 2 mg of estradiol benzoate (EB) at the begging of the protocol. Eight days later (D21), the Resynch group was checked for corpus luteum blood flow by color Doppler ultrasonography, and in those detected as non-pregnant, the protocol was completed and a 2nd TAI was performed at D23. Pregnancy diagnosis was later (D30) performed by B-mode ultrasonography in the control group and confirmed in the presumptive pregnant cows from the 1st TAI of the Resynch group. The remaining cows were checked for pregnancy 30 days after the 2nd TAI (experimental Day 53). The statistical model to explain conception rate considered the effects of Group (Control or Resynch), Farm, Parity (primiparous or multiparous), Sire, Technician (who perform AI), TAI Lot and pertinent interactions (Group*Parity, Group*Farm and Group*TAI Lot). The statistical analyses of the model were performed using the Proc Glimmix (SAS virtual University Edition). The conception rate for the 1st TAI was similar (P > 0.4) between Control (50.3%, 216/429) and Resynch group (52.6%, 527/1002). The positive predictive diagnostic on D21 showed high relation with PD30 (90.7%, 527/581). In Resynch group, non-pregnant cows (n = 421, 1002 minus 581) were re-inseminated. The conception rate of the 2nd TAI (42.8%, 180/421) was affected (P < 0.002) by side effects of the Farm (48.5 vs. 33.1%) and Parity (51.2 vs. 40.3%, for multiparous vs. primiparous, p < 0.001). Nevertheless, after the 2 TAIs of the Resynch group, the cumulative conception rate was 70.5% (707/1002). In conclusion, the early resynchronization of cows with a low (1 mg) EB dose and progesterone device at D13 after TAI can be used as a strategy to reduce conception interval in beef cattle, and thus to increase the number of pregnant cows from artificial insemination after the breeding season.

SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019).

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.