Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in singlecenter experience

We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM). Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin-eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging. Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin-eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%. The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor borde

Hypofractionated radiation therapy and temozolomide in patients with glioblastoma and poor prognostic factors. A prospective, single-institution experience

Background: Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods: GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5-2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m2/day of temozolomide were administered. Results: Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50-70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3-5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions: Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness

Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes

Objective To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED). Methods and results Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1-year all-cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in-hospital all-cause mortality, prolonged hospitalisation, 7-day post-discharge ED revisit for AHF and 30-day post-discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm+ wet, 1929 (17.1%) cold+ wet, 675 (6.0%) warm+ dry, and 99 (0.9%) cold+ dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm+ wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1-year mortality was 30.8%, and compared to warm+ dry, the adjusted hazard ratios were significantly increased for cold+ wet (1.660; 95% confidence interval 1.400-1.968) and cold+ dry (1.672; 95% confidence interval 1.189-2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in-hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk. Conclusions Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival

Burden and challenges of heart failure in patients with chronic kidney disease. A call to action

Patients with the dual burden of chronic kidney disease (CKD) and chronic congestive heart failure (HF) experience unacceptably high rates of symptom load, hospitalization, and mortality. Currently, concerted efforts to identify, prevent and treat HF in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this review paper endorse the need for a dedicated cardiorenal interdisciplinary team that includes nephrologists and renal nurses and jointly manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for guidelines and best clinical practice models from major cardiology and nephrology professional societies, as well as for research funding in both specialties to focus on the needs of future therapies for HF in CKD patients. The implementation of crossspecialty educational programs across all levels in cardiology and nephrology will help train future specialists and nurses who have the ability to diagnose, treat, and prevent HF in CKD patients in a precise, clinically effective, and cost-favorable manner.Los pacientes con enfermedad renal crónica (ERC) que desarrollan insuficiencia cardíaca (IC) congestiva crónica presentan cifras inaceptablemente altas de síntomas, hospitalización y mortalidad. Actualmente, se echan en falta iniciativas institucionales dirigidas a identificar, prevenir y tratar la IC en los pacientes con ERC de manera multidisciplinar, prevaleciendo las actuaciones de las especialidades individuales. Los autores de este artículo de revisión respaldan la necesidad de crear equipos multidisciplinares cardiorrenales, en los que participen nefrólogos y enfermeras renales, que gestionen colaborativamente las intervenciones clínicas apropiadas en los entornos de pacientes con ERC e IC hospitalizados y ambulatorios. Es necesario y urgente que se elaboren guías y modelos de práctica clínica sobre la ERC con IC por parte de las sociedades profesionales de cardiología y nefrología, así como financiación para la investigación concertada entre ambas especialidades sobre la necesidad de futuros tratamientos para la IC en pacientes con ERC. La implementación de programas educativos cardiorrenales a todos los niveles en cardiología y nefrología ayudará a formar a los futuros especialistas y enfermeras para que tengan la capacidad de diagnosticar, tratar y prevenir la IC en pacientes con ERC de manera precisa, clínicamente efectiva y económicamente favorabl

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Item does not contain fulltextBACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System

Objective In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system. Methods It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies. Results The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model. Conclusion Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters