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Artificial intelligence (AI)‐based systems applied to histopathology whole‐slide images have the potential to improve patient care through mitigation of challenges posed by diagnostic variability, histopathology caseload, and shortage of pathologists. We sought to define the performance of an AI‐based automated prostate cancer detection system, Paige Prostate, when applied to independent real‐world data. The algorithm was employed to classify slides into two categories: benign (no further review needed) or suspicious (additional histologic and/or immunohistochemical analysis required). We assessed the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) of a local pathologist, two central pathologists, and Paige Prostate in the diagnosis of 600 transrectal ultrasound‐guided prostate needle core biopsy regions (‘part‐specimens’) from 100 consecutive patients, and to ascertain the impact of Paige Prostate on diagnostic accuracy and efficiency. Paige Prostate displayed high sensitivity (0.99; CI 0.96–1.0), NPV (1.0; CI 0.98–1.0), and specificity (0.93; CI 0.90–0.96) at the part‐specimen level. At the patient level, Paige Prostate displayed optimal sensitivity (1.0; CI 0.93–1.0) and NPV (1.0; CI 0.91–1.0) at a specificity of 0.78 (CI 0.64–0.89). The 27 part‐specimens considered by Paige Prostate as suspicious, whose final diagnosis was benign, were found to comprise atrophy (n = 14), atrophy and apical prostate tissue (n = 1), apical/benign prostate tissue (n = 9), adenosis (n = 2), and post‐atrophic hyperplasia (n = 1). Paige Prostate resulted in the identification of four additional patients whose diagnoses were upgraded from benign/suspicious to malignant. Additionally, this AI‐based test provided an estimated 65.5% reduction of the diagnostic time for the material analyzed. Given its optimal sensitivity and NPV, Paige Prostate has the potential to be employed for the automated identification of patients whose histologic slides could forgo full histopathologic review. In addition to providing incremental improvements in diagnostic accuracy and efficiency, this AI‐based system identified patients whose prostate cancers were not initially diagnosed by three experienced histopathologists. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Evaluate tryptophan and thymine (TT) impact on carcinogenesis and intravesical BCG bladder cancer treatment.After identification of TT in vitro inhibitory effect in multiple cancer cell cultures, bladder cancer animal model was induced by MNU intravesical instillations and randomized into four groups: Control (Urothelial cancer was identified in 100%, 85.7%, 44.5%, and 37.5% of Control, TT, BCG, and BCG + TT groups, respectively. Cell proliferation marked by nuclear Ki-67 was higher in the Control compared to animals in the other groups (TT inhibit urothelial carcinogenesis and potentiate the intravesical BCG in the treatment of bladder cancer by reducing cell proliferation and activating TLRs.

Nitazoxanide (NTZ) has shown a promising antitumoral effect, the current study compared the anti-neoplastic effects of intravesical NTZ and BCG plus NTZ in NMIBC animal model. 30 rats, Fisher 344 were instilled with 4 intravesical doses of 1.5 mg/kg of N-methyl-N-nitrosourea (MNU) every 15 days for BC induction. The animals were divided into 3 groups (Group BCG 106 UFC – 1 mg of BCG; Group NTZ – 300 mg/kg of NTZ; Group NTZ + BCG – simultaneous treatment of BCG and NTZ) and received weekly intravesical treatment for 6 consecutive weeks. Animals were submitted to ultrasound imaging and euthanasia, their bladders were collected and histopathological, immunohistochemical tests (ki67 e c-Myc) and Western Blotting (PI3K, mTOR, and p-4E-BP) were performed. Histopathological tests showed 66.67%, 62.5% and 37.5% incidence of BC in animals treated with BCG, NTZ, and NTZ + BCG, respectively. Nuclear positivity for ki-67 in BC animals were 12.4% (IC 10.1–14.6%), 13.2% (IC 10.5–15.9%) and 8.8% (IC 6.0–11.6%) in BCG, NTZ and NTZ + BCG group, respectively (p = 0.063). Between animals with carcinoma, c-Myc strong positive was 40.10% in NTZ, 32.2% in BCG and 19.90% in the NTZ + BCG group (p

Background The relation between mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) - a common disease in extremely premature newborn (PTNB) - is well stabilished, but is unknown, however, how much time under MV influences the severity of the disease. Aim To define the duration under MV with greater chance to develop moderate to severe BPD in extremely PTNB and to compare clinical outcomes before and during hospitalization among patients with mild and moderate to severe BPD. Methods Fifty-three PTNB were separated into mild and moderate to severe BPD groups and their data were analyzed. Time under MV with a greater chance of developing moderate to severe BPD was estimated by the ROC curve. Perinatal and hospitalization outcomes were compared between groups. A logistic regression was performed to verify the influence of variables associated to moderate to severe BPD development, such as pulmonary hypertension (PH), gender, gestational age (GA) and weight at birth, as well the time under MV found with ROC curve. The result of ROC curve was validated using an independent sample (n = 16) by Chi-square test. Results Time under MV related to a greater chance of developing moderate to severe BPD was 36 days. Moderate to severe BPD group had more males (14 vs 5, p = 0,047), longer time under MV (43 vs 19 days, p p = 0,016), worse retinopathy of prematurity (grade 3, 2 vs 11, p = 0,003), longer hospital length of stay (109 vs 81,5 days, p p p p = 0,043). Among all variables included in logistic regression, only PH and MV n = 6) and 0% in mild BPD group (p = 0,0001). Conclusion Time under MV related to moderate to severe BPD development is 36 days, and worst outcomes are related to disease severity. PH and time under MV for more than 36 days are related to development of moderate to severe BPD.

INTRODUCTION: The obesity/overweight is closely related to poorer breast cancer prognosis, as well as higher mortality rates. In postmenopausal women, the main source of estrogen is in the adipose tissue. Due to that, overweight/obesity leads to an increase in breast cancer development and disease progression. This is a consequence of not only to high estrogen levels, but also to an increase in circulating factors that influence in inflammatory pathway activations and insulin resistance increase. OBJECTIVES: This study aims at analyzing weight and body composition variation in breast cancer women under nutritional monitoring during adjuvant chemotherapy (CT). METHOD/DESIGN: This is an observational, prospective study with estrogen receptor (ER) and/or progesterone receptor (PR) positives, HER2 negative breast cancer women, who underwent adjuvant CT, from 07/17/2018 to 06/19/2019. Nutritionists followed up these patients during all of CT cycles, and data on body composition were collected through bioelectric impedance in the first and last days of chemotherapy. In between cycles, body weight assessments, nutritional guidelines orientations adherence were checked against the information, which had been offered. RESULTS: 51 women were selected and 4 excluded according to study criteria (3 patients turned HER2 positive by FISH and 1 patient had metastatic cancer confirmation). By the data analysis, 36 patients completed chemotherapy. The CT regimens used were doxorrubicin, cyclophosphamide and paclitaxel (ACT) (59%), AC plus docetaxel (4%), cyclophosphamide, methotrexate and Fluorouracil (CMF) (10%), AC (6%) and docetaxel and cyclophosphamide (TC) (21%). The mean age was 51 years, with 12 women aged ≥ 60 years. At the beginning the mean Body Mass Index (BMI) was 27.94 kg / m2. 37% of them were classified as eutrophic, 33% were overweight and 30% obese, according to the World Health Organization (WHO) criteria. Weight gain was observed in 64% of patients, with a significant increase in lean mass (kg) as well as body water (in 75% of patients). There was a reduction in fat percentage due to the reduction of fat mass in kilos (52.8% of patients) and the increase of lean mass (kg). The mean BMI at the end of treatment was 27.08 kg / m2, with a decrease in obesity and eutrophic index (reduction of 5.8% and 32.9%, respectively) and an increase in overweight by 41.7%. If considered the weight variation per CT protocol, the women submitted to the ACT scheme had a higher prevalence of weight gain, distributed in lean mass (80%), body water (75%) and fat mass reduction in 55% of these patients. On the other hand, there was a reduction in the mean of BMI value between the first evaluation (26.7 kg / m2) and the last one (22.4 kg / m2), as well as a lower fat mass in 62.5% of women who were submitted to TC protocol. In addition, in CMF and AC protocol, only one patient in each regimen finished the treatment until the deadline. In this case, the results were immature and not been reported in this abstract. CONCLUSIONS: There was an improvement in body composition, considering lean and fat mass in the study population, probably due to the nutritional monitoring during all cycles of chemotherapy. Nutritional therapy certainly influenced adherence to better eating habits. Full data of the 51 patients will be presented during the meeting. It should reinforce the need of developing prospective controlled studies, targeting nutritional intervention in breast cancer treatment. Citation Format: Flavia Rocha Paes, Anna Nogueira Verano, Julia SM de Sá, Rafaela M Peixoto, Juliana CO Pena, Maria Clara A Zocrato, Patricia C Christo, Fernanda CMJ Oliveira, Bruno L Ferrari. Weight and body composition’s analysis in chemotherapy-treated women with breast cancer under nutritional follow up in a private oncology service in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-07.

Vascular Calcification (VC), low bone mass and fragility fractures are frequently observed in ageing subjects. Although this clinical observation could be the mere coincidence of frequent age-dependent disorders, clinical and experimental data suggest that VC and bone loss could share pathophysiological mechanisms. Indeed, VC is an active process of calcium and phosphate precipitation that involves the transition of the vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Among the molecules involved in this process, parathyroid hormone (PTH) plays a key role acting through several mechanisms which includes the regulation of the RANK/RANKL/OPG system and the Wnt/ß-catenin pathway, the main pathways for bone resorption and bone formation, respectively. Furthermore, some microRNAs have been implicated as common regulators of bone metabolism, VC, left ventricle hypertrophy and myocardial fibrosis. Elucidating the common mechanisms between ageing; VC and bone loss could help to better understand the potential effects of osteoporosis drugs on the CV system.

Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. Materials and Methods: This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. Results: The results showed a prevalence of male (N = 63, 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. Conclusions: This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted.

Evaluate tryptophan and thymine (TT) impact on carcinogenesis and intravesical BCG bladder cancer treatment. After identification of TT in vitro inhibitory effect in multiple cancer cell cultures, ...

INTRODUCTION AND OBJECTIVE:Toll-like receptor 4 (TLR-4) is a key urothelial trigger for innate immune response and its gene polymorphism and expression are inversely associated to bladder cancer (B...

Tumors escape from the immune system by decreasing CD8+ and increasing CD4+ T cells’ activity, druggable targets. Thermal ablation might activate tumor-specific T cells by raising the presentation of tumor-specific antigens and hindering tumor negative immune regulation. Our aim was to assess T cell infiltrate pre- and post-cryoablation in a prospective observational study. A total of 240 sextant prostate biopsies cores (12 cores/patient) were collected from 10 unilateral prostate cancer patients (T1c, PSA density

Background: The COVID-19 pandemic remains a public health emergency of global concern, with higher mortality rates in cancer patients as compared to the general population. However, early mortality of COVID19 in cancer patients has not been compared to historical real-world data from oncology population in pre-pandemic times. Methods: Longitudinal multicenter cohort study of patients with cancer and confirmed COVID-19 from Oncoclinicas Group in Brazil from March to December 2020. The primary endpoint was 30-day mortality after isolation of the SARS-CoV-2 by RT-PCR. As historical control, we selected patients from Oncoclinicas Data Lake treated before December 2019 and propensity score-matched to COVID-19 cases (3:1) based on the following clinical characteristics: age, gender, tumor type, disease setting (curative or palliative), time from diagnosis of cancer (or metastatic disease) to COVID-19 infection. Results: In total, 533 cancer patients with COVID-19 were prospectively registered in the database, with median age 60 years, 67% females, most frequent tumor types breast (34%), hematological (16%), gastrointestinal (15%), genitourinary (12%) and respiratory tract malignancies (10%). Most patients were on active systemic therapy or radiotherapy (84%), largely for advanced or metastatic disease (55%). In the overall population, early death rate was 15%, which was numerically higher than the Brazilian general population with COVID-19 diagnosis in 2020 (2.5%). We were able to match 442 cancer patients with COVID-19 to 1,187 controls with cancer from pre-pandemic times. The 30-day mortality rate was 12.4% in COVID-19 cases as compared to 5.4% in pre-pandemic controls with cancer (Odds Ratio 2.49, 95%CI 1.67 - 3.70;P value < 0.01, Power 97.5%). COVID-19 cancer patients had significantly higher death events than historical controls (Hazard Ratio 2.18, 95%CI 1.52 - 3.12;P value < 0.01, Power 99.7%), particularly from 20 to 30 days after diagnosis of the infection. Conclusions: Cancer patients with COVID-19 have an excess mortality 30 days after the infection when compared to matched cancer population from pre-pandemic times and the general population with COVID-19, reinforcing the need for priority vaccination in public health strategies. Legal entity responsible for the study: Oncoclinicas Group. Funding: Amgen. Disclosure: All authors have declared no conflicts of interest.

PURPOSEThe COVID-19 pandemic remains a public health emergency of global concern. Determinants of mortality in the general population are now clear, but specific data on patients with cancer remain limited, particularly in Latin America.MATERIALS AND METHODSA longitudinal multicenter cohort study of patients with cancer and confirmed COVID-19 from Oncoclínicas community oncology practice in Brazil was conducted. The primary end point was all-cause mortality after isolation of the SARS-CoV-2 by Real-Time Polymerase Chain Reaction (RT-PCR) in patients initially diagnosed in an outpatient environment. We performed univariate and multivariable logistic regression analysis and recursive partitioning modeling to define the baseline clinical determinants of death in the overall population.RESULTSFrom March 29 to July 4, 2020, 198 patients with COVID-19 were prospectively registered in the database, of which 167 (84%) had solid tumors and 31 (16%) had hematologic malignancies. Most patients were on active systemic therapy or radiotherapy (77%), largely for advanced or metastatic disease (64%). The overall mortality rate was 16.7% (95% CI, 11.9 to 22.7). In univariate models, factors associated with death after COVID-19 diagnosis were age ≥ 60 years, current or former smoking, coexisting comorbidities, respiratory tract cancer, and management in a noncurative setting ( P < .05). In multivariable logistic regression and recursive partitioning modeling, only age, smoking history, and noncurative disease setting remained significant determinants of mortality, ranging from 1% in cancer survivors under surveillance or (neo)adjuvant therapy to 60% in elderly smokers with advanced or metastatic disease.CONCLUSIONMortality after COVID-19 in patients with cancer is influenced by prognostic factors that also affect outcomes of the general population. Fragile patients and smokers are entitled to active preventive measures to reduce the risk of SARS-CoV-2 infection and close monitoring in the case of exposure or COVID-19-related symptoms.

Background The Toll-like receptor (TLR)2/4 agonist bacillus Calmette-Guerin (BCG), although not failure proof, has been the most efficient immunomodulatory treatment of immunogenic nonmuscle-invasive bladder cancer (NMIBC) for > 40 years. We investigated the role of the immunomodulatory molecule TLR7 agonist imiquimod through the BCG key receptors TLR2/4 and the main downstream molecules of the mammalian target of rapamycin pathway in NMIBC treatment. Materials and Methods A total of 40 Fischer-344 rats, 7 weeks old, received 4 doses of 1.5 mg/kg N-methyl-N-nitrosourea intravesically on weeks 0, 2, 4, and 6 for cancer induction. At week 8, the rats were randomized into 4 groups (10 per group) and treated intravesically once a week for 6 weeks: control (0.2 mL of vehicle); BCG (2 × 106 colony-forming units Connaught strain in 0.2 mL); imiquimod (20 mg/kg in 0.2 mL), and associated treatment BCG plus imiquimod in 0.2 mL. The bladders were extracted and analyzed for histopathology, immunohistochemistry, cell proliferation (Ki-67), apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling [TUNEL]), and immunoblotting for TLR2, TLR4, p-P70S6K, and p-4E-BP1 proteins. Results The histopathology results showed that BCG and imiquimod decreased bladder tumorigenesis compared with the control group, with a proliferation decrease (Ki-67) and an apoptosis increase (TUNEL). BCG upregulated TLR2/4, imiquimod upregulated TLR4, and both downregulated P70S6K1. Conclusion Imiquimod is able to efficiently decrease bladder carcinogenesis through upregulation of TLR7/4 and downregulation of P70S6K1 protein, generating new perspectives to boost BCG effects in the future.

e24004 Background: Early palliative care has shown an improvement in the quality of life of cancer patients by reducing overtreatment at the end of life and improving symptomatic control. Little is known about the quality of death in developing countries. End-of-life cancer care varies widely, and very few centers evaluate it systematically. The aim of the present study is to analyze the impact of follow-up of cancer patients by an outpatient palliative care team (OPCT) on the end-of-life outcomes at a Cancer Center in Brazil. Methods: We retrospectively retrieved data from electronic medical records of cancer patients who were treated at a Cancer Center in Brazil and who died from cancer or associated complications during the year of 2020. They were divided into two groups: OPCT and No-OPCT. OPCT group was followed-up by a multidisciplinary team composed of physician, nurse, physiotherapist, psychologist, nutritionist, social worker, speech-language therapist, and pharmacist, who regularly evaluated cancer patients during their treatments at outpatient setting. During COVID-19 pandemic, some patients were evaluated by telemedicine appointments. No-OPCT group was followed-up by cancer physicians exclusively. We performed univariate comparisons and multivariate analysis by Cox proportional hazards model. p < 0.05 was deemed as statistically significant. Results: A total of 315 patients were included in the study: OPCT (N=122) and No-OPCT (N=193). The groups were well balanced in relation to median age (61yo vs 63yo), gender (women: 51% vs 54%), and TNM stage (stage IV: 69% vs 65%). Gastrointestinal and breast cancers were the most prevalent. The rate of home death was 44% in the OPCT group, compared to 16% in the No-OPCT group (p

BACKGROUND Alzheimer's disease (AD) and frontotemporal dementia (FTD) are leading causes of cognitive decline. Optical coherence tomography (OCT) allows the measurement of thickness of retinal neuroaxonal layers. While in AD and mild cognitive impairment (MCI), retinal nerve fiber layer (RNFL) thinning is frequently reported, less information is available on ganglion cell layer-inner plexiform layer (GCL-IPL). Data on FTD are lacking. OBJECTIVE To obtain cross-sectional information on RNFL and GCL-IPL thickness among MCI, AD, FTD, and healthy controls (HC), and their correlations with dementia severity. METHODS Peripapillary OCT scans were obtained in 27 MCI, 39 AD, 17 FTD, 49 HC using high-definition Heidelberg Spectral-domain OCT, with RNFL and GCL-IPL thickness measurement. Statistical analysis tested group effects and correlation with gender, disease duration and severity (Mini-Mental State Examination, MMSE). RESULTS RNFL showed a significant group effect [F(4,132) = 3.786, p = 0.006], being reduced versus controls in MCI (p = 0.033), moderate AD (p = 0.025), and FTD (p

The objective was to determine the reduction of tophi in patients undergoing drug therapy in correlation with urate serum levels through ultrasound examination. A total of 31 male patients, between the ages of 33 to 77 years, with tophaceous gout were evaluated between 2005 and 2009, 11 of which were selected. Ultrasound examinations of visible tophi and evaluations of serum uric acids levels were performed annually on each patient. There was a statistically significant difference between measurements 1, 2, 3 and measurement 4 and between measurements 4 and 5. A strong significant positive association was seen between variation of tophus size and the reduction of serum uric acid levels.

Made available in DSpace on 2019-10-04T12:14:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-01 This prospective cohort study aimed to assess the association of admission hypothermia (AH) with death and/or major neonatal morbidities among very low birth weight (VLBW) preterm infants based on the relative performance of 20 centers of the Brazilian Network of Neonatal Research. This is a retrospective analysis of prospectively collected data using the database registry of the Brazilian Network on Neonatal Research. Center performance was defined by the relative mortality rate using conditional inference trees. A total of 4356 inborn singleton VLBW preterm infants born between January 2013 and December 2016 without malformations were included in this study. The centers were divided into two groups: G1 (with lower mortality rate) and G2 (with higher mortality rate). Crude and adjusted relative risks (RR) and 95% confidence intervals (95%CI) were estimated by simple and multiple log-binomial regression models. An AH rate of 53.7% (19.8-93.3%) was significantly associated with early neonatal death in G1 (adjusted RR 1.41, 95% CI 1.09-1.84) and G2 (adjusted RR 1.29, 95%CI 1.01-1.65) and with in-hospital death in G1 (adjusted RR 1.29, 95%CI 1.07-1.58). AH was significantly associated with a lower frequency of necrotizing enterocolitis (adjusted RR 0.58, 95%CI 38-0.88) in G2.Conclusion: AH significantly associated with early neonatal death regardless of the hospital performance. In G2, an unexpected protective association between AH and necrotizing enterocolitis was found, whereas the other morbidities assessed were not significantly associated with AH. Univ Estadual Campinas, Fac Ciencias Med, Dept Pediat, Campinas, SP, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, Ave Bandeirantes 3900, BR-14049900 Sao Paulo, Brazil Univ Fed Sao Paulo, Div Neonatal Med, Sao Paulo, Brazil Univ Sao Paulo, Dept Pediat, Sch Med, Sao Paulo, Brazil Inst Crianca, Ave Dr Eneas de Carvalho Aguiar,647 Pinheiros, BR-05403000 Sao Paulo, Brazil Univ Fed Rio Grande do Sul, HCPA, Div Neonatol, Rua Silva Jardim 1155-701, BR-90450071 Porto Alegre, RS, Brazil Maternidade Hilda Brandao, Fac Ciencias Med Minas Gerais, Dept Pediat, Belo Horizonte, MG, Brazil Hosp Geral Pirajussara, Neonatal Unit, Taboao Da Serra, Brazil Univ Estadual Paulista, Fac Med Botucatu, Div Neonatol, Botucatu, SP, Brazil Univ Fed Uberlandia, Dept Pediat, Uberlandia, MG, Brazil Univ Fed Maranhao, Dept Pediat, Sao Luis, Brazil Pontificia Univ Catolica Rio Grande do Sul, Fac Med, Hosp Sao Lucas, Dept Pediat, Porto Alegre, RS, Brazil Univ Estado Rio de Janeiro, Hosp Univ Pedro Ernesto, Dept Pediat, Rio De Janeiro, Brazil Inst Med Integral Prof Fernando Figueira, Dept Pediat, Recife, PE, Brazil Fundacao Oswaldo Cruz, Div Neonatol, Rio De Janeiro, Brazil Univ Estadual Londrina, Dept Pediat, Univ Hosp, Curitiba, Parana, Brazil Hosp Estadual Diadema, Neonatal Unit, Diadema, Brazil Univ Fed Parana, Hosp Clin, Dept Pediat, Curitiba, Parana, Brazil Univ Fed Minas Gerais, Div Neonatol, Belo Horizonte, MG, Brazil Hosp Estadual Sumare, Neonatal Div, Sumare, Brazil Univ Estadual Paulista, Fac Med Botucatu, Div Neonatol, Botucatu, SP, Brazil

Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.

Context: Clinical data from controlled trials report an improvement in QoL in patients with CLL in ibrutinib monotherapy. Reallife evidence is necessary to confirm this data. Objective: The disease control when treatment is initiated could lead to decreasedfatigue. It is likely that treatment with ibrutinib could result in animprovement in QoL in our real-world population. Primaryobjective: evaluate impact of ibrutinib treatment in QoL. Wedefined a clinically meaningful improvement 3 points in FACITfatigue score. Secondary Endpoints: Detect a 10% improvement byEQ5D VAS. Correlate baseline and follow-up hemoglobin levels(meaningful improvement 1g/dL). Design: This is a prospective,longitudinal, single arm study enrolling consecutive CLL patientsunder ibrutinib monotherapy either as first or further line oftreatment. Median follow-up was 7 months (range 1-28). Setting:Patients are recruited in an academic referral center in BuenosAires. Interventions: QoL was explored with FACIT-fatigue andEQ5D visual-analogue-scale (VAS) questionnaires (with copyrightpermission). Assessment by results reported by patient questionnaires are completed on months 0-1-3-6 and 12 since the beginningof treatment. Main Outcomes Measures: We are reporting preliminary results after 3 months of treatment compared to baseline.Statistical Analysis: data was analyzed with the Sign Test (BinomialTest). Results: A total of 21 CLL patients who started ibrutinibbetween 2016 and 2018 were included. Median age was 75 years(range 57-84); 12 patients (57%) were males. Ibrutinib was first-linetherapy in 7 patients (33%), second-line in 7 patients (33%) and 7patients (33%) received 3 previous lines. After 3 months oftreatment, the median change in FACIT-fatigue score 3 pointswas reached in 13 patients (62%) as compared to baseline(p=0.024). After 3 months of treatment there was no evidence of amedian change >10% on the EQ5D VAS (p=0.593) nor a significant improvement on hemoglobin level (p=0.105).Conclusions: These results suggest an early improvement of fatiguewithin the first 3 months of treatment with ibrutinib. Longerfollow-up and larger number of patient are necessary to confirm thisdata and determine the further improvements of QoL withcontinuous treatment and correlation with hemoglobin changes. Fil: Mela Osorio, Maria Jose. Fundación Para Combatir la Leucemia; Argentina Fil: Pavlovsky, Carolina. Fundación Para Combatir la Leucemia; Argentina Fil: Pavlovsky, Astrid. Fundación Para Combatir la Leucemia; Argentina Fil: Fernandez, Isolda. Fundación Para Combatir la Leucemia; Argentina Fil: Massa, Federico Sackmann. Fundación Para Combatir la Leucemia; Argentina Fil: Ferrari, Luciana. Fundación Para Combatir la Leucemia; Argentina Fil: Juni, Mariana. Fundación Para Combatir la Leucemia; Argentina Fil: Riddick, Maximiliano Luis. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Matemáticas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pavlovsky, Miguel A.. Fundación Para Combatir la Leucemia; Argentina

Objective: The aim of this retrospective cohort study was to evaluate the obstetrical and perinatal outcomes of vaginal birth in case of pregnancies achieved after prior myomectomy. We also analyzed how operative characteristics at the time of surgery might influence the choice of obstetricians about mode of delivery. Study design: We analyzed retrospectively all women who underwent laparoscopic (LPS) or laparotomic (LPT) myomectomy between January 2002 and December 2014, in a network of three Institutions belonging to the University of Milano Bicocca, Italy. Women were contacted by phone interview and only cases with available follow-up data and who had a subsequent pregnancy were included. Operative characteristics and subsequent obstetrical outcomes were recorded and analyzed. Results: 469 women who underwent myomectomy were contacted by phone interview, and 152 pregnancies were achieved after surgery, 96 after LPS and 56 after LPT. A total of 110 pregnancies ended in deliveries at ≥24 weeks. Seventy-three (66.4%) women had trial of labor after myomectomy (TOLAM), while 24 (21.8%) had a planned cesarean delivery (CD). Sixty-six (90.4%) of the TOLAM cases successfully accomplished vaginal delivery. No cases of uterine rupture (UR) were reported, and all deliveries ended in live births. The incidence of Neonatal Intensive Care Unit admission was 14.5% (16/110), with no cases of perinatal death. Comparing the surgical details at the time of myomectomy, the incidence of uterine cavity entered was significantly higher in planned CD group compared to TOLAM cases (p < 0.001). No other significant difference between the two groups was reported. Conclusions: A successful vaginal delivery was accomplished by 90.4% of women who had TOLAM, without any case of UR or severe maternal and perinatal complications. TOLAM may be considered and offered as feasible and relatively safe option. Obstetricians’ attitude toward mode of delivery after prior myomectomy seems to be influenced by the reported entry into the uterine cavity at the time of surgery

The aim of this study was to explore the efficacy of intravesical Thalidomide (immunomodulatory, anti-inflammatory and anti-angiogenic) added to BCG using an immune competent autochthonous orthotopic NMIBC animal model. Female Fischer 344 rats, 7 weeks of age, received every 2 weeks for four times, a dose of 1.5 mg/kg of N-methyl-N-nitrosourea (MNU) intravesically. The rats were randomized into four groups (n = 10 per group) to receive intravesical treatment once a week for 6 weeks as follows: control (0.2 ml vehicle), BCG (2 × 106 CFU of Connaught strain in 0.2 ml), Thalidomide (20 mg/kg in 0.2 ml) and BCG-Thalidomide in 0.2 ml. At week 15, bladders were collected for histopathology, cell turnover index by immunohistochemistry and immunoblotting quantification of 4E-BP1 and p70S6K1 for downstream mTOR proliferation signaling and HIF and VEGF for angiogenesis pathway. Thalidomide-BCG association showed a trend for normal histopathology and down-regulation of cell turnover, p70S6K1, HIF-1 and VEGF. 4E-BP1 was up-regulated by treatment, especially in the Thalidomide groups, supporting that its regulation occurs independently of p70S6K1 on mTOR pathway in NMIBC. Intravesical BCG-Thalidomide might represent a significant increment in NMIBC treatment, suggesting p70S6K1, HIF-1 and VEGF as potential molecular target candidates in a clinically relevant immune competent NMIBC model.

ResumoO xantoma no tendão calcâneo é uma doença rara e tem uma alta associação com hiperlipidemia primária. O diagnóstico precoce é fundamental para o início do tratamento e para alterar o curso da doença. Os exames de imagem podem auxiliar nesse diagnóstico. Este estudo relata o caso de um homem de 60 anos apresentando nódulos indolores nos cotovelos e tendões calcâneos, sem crises típicas de gota, acompanhado no ambulatório de doenças microcristalinas da Unifesp para esclarecimento diagnóstico. Os testes laboratoriais solicitados apresentavam dislipidemia. Ultrassom (US) mostrou espessamento difuso dos tendões calcâneos com áreas hipoecoicas. Ressonância magnética (RM) mostrou espessamento difuso dos tendões, com áreas de sinal intermediário e padrão reticulado no interior. Os exames de imagem mostraram aspectos relevantes no diagnóstico de xantoma, auxiliando no diagnóstico diferencial.AbstractThe Achilles tendon xanthoma is a rare disease and has a high association with primary hyperlipidemia. An early diagnosis is essential to start treatment and change the disease course. Imaging exams can enhance diagnosis. This study reports the case of a 60‐year‐old man having painless nodules on his elbows and Achilles tendons without typical gout crisis, followed in the microcrystalline disease clinic of Unifesp for diagnostic workup. Laboratory tests obtained showed dyslipidemia. The ultrasound (US) showed a diffuse Achilles tendon thickening with hypoechoic areas. Magnetic resonance imaging (MRI) showed a diffuse tendon thickening with intermediate signal areas, and a reticulate pattern within. Imaging studies showed relevant aspects to diagnose a xanthoma, thus helping in the differential diagnosis.

Made available in DSpace on 2018-11-26T17:55:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-18 Health Ministry of Brazil (Ministerio da Saude do Brasil) Objective: To analyze unfavorable outcomes at hospital discharge of preterm infants born at Brazilian public university centers.Methods: Prospective cohort of 2646 inborn infants with gestational age 23-33 weeks and birth weight 400-1499g, without malformations, born at 20 centers in 2012-2013. Unfavorable outcome was defined as in-hospital death or survival at hospital discharge with 1 major morbidities: bronchopulmonary dysplasia (BPD) at 36 corrected weeks, intraventricular hemorrhage (IVH) grades 3-4, periventricular leukomalacia (PVL) or surgically treated retinopathy of prematurity (ROP).Results: Among 2646 infants, 1390 (53%) either died or survived with major morbidities: 793 (30%) died; 497 (19%) had BPD; 358 (13%) had IVH 3-4 or PVL; and 84 (3%) had ROP. Logistic regression adjusted by center showed association of unfavorable outcome with: antenatal steroids (OR 0.70; 95%CI 0.55-0.88), C-section (0.72; 0.58-0.90), gestational age

Objectives To assess the efficacy of high-frequency (20Hz) brain stimulation on lower limb motor function in subjects with chronic (>6mo) subcortical stroke. Design Double-blind, placebo-controlled crossover study. Setting University hospital. Participants Right-handed subjects (N=10) affected by a first-ever subcortical stroke in the territory of the middle cerebral artery were included in this study. Interventions Repetitive transcranial magnetic stimulation (rTMS) was delivered with the H-coil, specifically designed to target deeper and larger brains regions. Each subject received both real and sham rTMS in a random sequence. The 2 rTMS cycles (real or sham) were composed of 11 sessions each, administered over 3 weeks and separated by a 4-week washout period. Main Outcome Measures Lower limb functions were assessed by the lower limb Fugl-Meyer scale, the 10-m walk test, and the 6-minute walk test before and 1 day after the end of each treatment period, as well as at a 4-week follow-up. Results Real rTMS treatment was associated with a significant improvement in lower limb motor function. This effect persisted over time (follow-up) and was significantly greater than that observed with sham stimulation. A significant increase in walking speed was also found after real rTMS, but this effect did not reach statistical significance in comparison with the sham stimulation. Conclusions These data demonstrated that 3 weeks of high-frequency deep rTMS could induce long-term improvements in lower limb functions in the chronic poststroke period, lasting at least 1 month after the end of the treatment.

The objective of the study was to illustrate the applicability and significance of the novel Lewis urothelial cancer model compared to the classic Fisher 344. Fischer 344 and Lewis females rats, 7 weeks old, were intravesical instilled N-methyl-N-nitrosourea 1.5 mg/kg every other week for a total of four doses. After 15 weeks, animals were sacrificed and bladders analyzed: histopathology (tumor grade and stage), immunohistochemistry (apoptotic and proliferative indices) and blotting (Toll-like receptor 2—TLR2, Uroplakin III—UP III and C-Myc). Control groups received placebo. There were macroscopic neoplastic lesions in 20 % of Lewis strain and 70 % of Fischer 344 strain. Lewis showed hyperplasia in 50 % of animals, normal bladders in 50 %. All Fischer 344 had lesions, 20 % papillary hyperplasia, 30 % dysplasia, 40 % neoplasia and 10 % squamous metaplasia. Proliferative and apoptotic indices were significantly lower in the Lewis strain (p

Comparou-se a mortalidade infantil evitável nas coortes de nascimentos de 2000/2001 e de 2007/2008, em Londrina-PR. Dados sobre nascidos vivos e óbitos infantis foram vinculados em base de dados única e as causas básicas de morte foram agrupadas conforme a Lista Brasileira de Causas de Mortes Evitáveis por Intervenções do Sistema Único de Saúde. Calculou-se a variação percentual das taxas de mortes entre os biênios e usou-se a técnica de análise de correspondência. As proporções de óbitos evitáveis foram de 71,6% em 2000/2001 e de 65,5% em 2007/2008. A taxa de mortalidade evitável por atenção à mulher na gestação predominou nos dois biênios, com incremento de 16,7%. Houve declínio das taxas de mortalidade evitável pelas demais causas. A análise de correspondência mostrou, em 2000/2001, um perfil de mortes representado principalmente por causas evitáveis por atenção à mulher no parto e por adequada promoção/atenção à saúde, enquanto que, em 2007/2008, por causas evitáveis por adequada atenção à mulher na gestação, especialmente entre os nascidos com baixo peso, e não claramente evitáveis entre os com peso adequado. Apesar da diminuição da mortalidade por algumas causas evitáveis, são necessárias medidas para aumentar a qualificação da atenção durante a gestação.

Background Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. Objective To evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. Methods Twenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. Results No drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P Conclusions High-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

While governments in sub-Saharan Africa work to provide in-country relief for the HIV/AIDS crisis, much health care and infrastructure comes from local or international non-governmental organizations (NGOs). The literature on NGOs suggests that collaboration increases their efficacy. Many non-Catholic NGOs do not work collaboratively with Catholic NGOs on HIV/AIDS, though the Catholic Church has rich and varied resources at its disposal for relief work. Observers often characterize the incompatibility of Catholic and non-Catholic NGOs as tactical, especially with regard to condom use. However, divergent issue framing is a critical and more fundamental distinction between the two groups. Contrasting the Catholic Church’s unique spiritual frame with the scientific frame of many non-Catholic NGOs highlights the epistemological and teleological differences between the two. Reconciling these differing approaches, or finding ways to cooperate despite them, is a key element of promoting broader NGO collaboration on HIV/AIDS relief work. This theoretical analysis suggests directions for future empirical research.

To describe the different and lesser-known ultrasound features of tophi in chronic tophaceous gout. Ultrasound images of 138 affected areas were analyzed from 31 patients with gout, using high-quality broadband linear transducers (frequency range of 8–14 MHz). Tophi were classified relative to echogenicity, echotexture, contours, number and the presence or absence of hypoechoic halo. The duration of illness was correlated with the presence of calcifications in tophi. Hyperechoic tophi were seen in 133 areas (96.3%); these were most frequently hyperechoic and heterogeneous (37.6%) or hyperechoic and heterogeneous with calcification (32.6%). Contours were found to be poorly defined in 115 (83.3%) areas. Multiple grouped tophi were seen in 85 areas (61.6%) and 50 areas (36.2%) had individual tophi. In 77 examined areas (55.8%), there was a hypoechoic halo around the tophi. There was no correlation between illness duration and presence of calcifications on tophi. Tophi are generally hyperechoic, heterogeneous, with poorly defined contours, multiple grouped and surrounded by an anechoic halo. Individual tophus and the absence of association between illness duration and the presence of calcification are newly described features. This study of tophaceous gout by ultrasound may contribute to the diagnostic elucidation of patients with clinically atypical gout and show its diverse characteristic forms of presentation.

ObjectiveTo describe and classify the varied ultrasound features of tendinous involvement in relation to tophi in chronic tophaceous gout so that they are better recognised.MethodsUltrasound images of 138 affected areas from 31 patients with chronic tophaceous gout were analysed using high-quality broadband linear transducers. The relationship between tendon and tophi was classified, and the inter-observer agreement regarding classification was analysed.ResultsTophi envelopment in the tendon was the most frequent characteristic (45%) followed by no relationship between tophi and tendon (41%), tophi at the insertion site of the tendon (7%), extrinsic compression (6%) and tophi within the tendon (1%). The inter-observer concordance on classification of the relationship between tophi and tendon was measured using McNemar’s test withP χ2 = 30.0, degree of freedom = 9) and kappa test = 0.627 (P ConclusionTophi generally envelope the tendon or there is no relationship between them. Tophi can also be found at the insertion site of the tendon, cause extrinsic compression or be located inside the tendon. There is substantial inter-observer agreement for ultrasound classification of tendon involvement by tophi. This study contributes to diagnostic elucidation and shows the diverse characteristic forms of tendon involvement by tophi.

The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBelCGRP neurons caused wakefulness, whereas optogenetic inhibition of PBelCGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBelCGRP terminals identified a network of forebrain sites under the control of a PBelCGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea. VIDEO ABSTRACT.

Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial.To assess the impact of mutational status in response rates and development of adverse events during long-term use of anagrelide.We retrospectively evaluated 67 patients with essential thrombocythemia treated with anagrelide during 68 (4-176) months.Mutational frequencies were 46.3%, 28.3%, and 1.5% for JAK2V617F, CALR and MPL mutations. Anagrelide yielded a high rate of hematologic responses, which were complete in 49.25% and partial in 46.25%, without differences among molecular subsets. The rate of thrombosis during treatment was one per 100 patient-years, without excess bleeding. Anemia was the major adverse event, 30.3% at 5-yr follow-up, being more frequent in CALR(+) (P0.05). Myelofibrotic transformation developed in 14.9% (12.9%, 21%, and 12.5% in JAK2V617F(+), CALR(+), and triple-negative patients, respectively, P = NS) and those treated60 months were at higher risk, OR (95% CI) 9.32 (1.1-78.5), P0.01, indicating the need for bone marrow monitoring during prolonged treatment.Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.

PURPOSE: The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). METHODS: We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. RESULTS: Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. CONCLUSION: In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.

Apesar dos avanços tecnológicos nas últimas décadas, a mortalidade neonatal é responsável por mais de 2/3 dos óbitos infantis, principalmente em regiões onde o coeficiente de mortalidade infantil é baixo. O objetivo deste estudo é analisar os óbitos neonatais do Município de Londrina, Paraná, Brasil, em três períodos, iniciando por 1994 ano de implantação das UTIs pediátrica e neonatal no município. Foram utilizados dados do SINASC e análise individualizada de cada declaração de óbito neonatal dos anos de 1994, 1999 e 2002. Verificou-se redução do número de nascimentos no município, o índice de baixo peso aumentou de 7,7 para 8,8%, e o de prematuridade aumentou de 6,3 para 8,4%. Houve aumento de gestações múltiplas. A taxa de cesariana variou de 48 a 52%. O coeficiente de mortalidade neonatal declinou de 10,1 para 6,4 por mil nascidos vivos. A maioria dos óbitos são evitáveis, principalmente, por adequada atenção na gravidez. Conclui-se que está ocorrendo uma melhora progressiva na assistência ao recém-nascido, e isso é um bom indicador das ações de saúde do município.

Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-12-01Bitstream added on 2015-02-02T13:07:52Z : No. of bitstreams: 1 S0021-75572014000600616.pdf: 538774 bytes, checksum: f77d33775a668b04ad4851c5a1d3e6fc (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Objetivo Analisar os efeitos da terapêutica adotada para o canal arterial (CA) em recém-nascidos (RN) < 1.000gadmitidos em unidades neonatais (UN) da Rede Brasileira de Pesquisas Neonatais (RBPN), sobre os desfechos: óbito, displasia broncopulmonar (DBP), hemorragia intraventricular grave (HIVIII/IV), retinopatia da prematuridade cirúrgica (ROPcir), enterocolite necrosante cirúrgica (ECNcir) e o desfecho combinado óbito e DBP. Métodos Estudo multicêntrico, de coorte, coleta de dados retrospectiva, incluindo RN de 16 UN da RBPN de 01/01/2010 a 31/12/2011, PN < 1.000 g, idade gestacional (IG) < 33 semanas e diagnóstico ecocardiográfico de PCA. Excluídos: óbitos ou transferências até o terceiro dia de vida, infecções congênitas ou malformações. Grupos: G1 – conservadora (sem intervenção medicamentosa ou cirúrgica), G2 – farmacológica (indometacina ou ibuprofeno) e G3 – cirúrgico (com ou sem tratamento farmacológico anterior). Analisou-se: uso de esteroide antenatal, parto cesárea, PN, IG, Apgar5′ < 4, sexo masculino, SNAPPE II, síndrome do desconforto respiratório (SDR), sepse tardia, ventilação mecânica (VM), surfactante < 2 horas de vida, tempo de VM e os desfechos: óbito, dependência de oxigênio com 36 semanas (DBP36s), HIV III/IV, ROPcir, ECNcir e óbito/DBP36s. Estatística: Teste t-Student, Qui-Quadrado ou teste Exato de Fisher. Testes de Regressão Binária Logística e Regressão Múltipla Stepwise Backward. MedCalc (Medical Calculator) software, versão 12.1.4.0.p < 0,05. Resultados Foram selecionados 1.097 RN e 494 foram incluídos: G1-187 (37,8%), G2-205 (41,5%) e G3-102 (20,6%). Verificou-se: maior mortalidade (51,3%) no G1 e menor no G3(14,7%); maior frequência DBP36s (70,6%) e ROPcir (23,5%) no G3; maior frequência de óbito/DBP36s no G2 (58,0%). As abordagens farmacológica (OR-0,29; 95%, IC-0,14-0,62) e conservadora (OR-0,34; 95%, IC- 0,14-0,79) foram protetoras somente para o desfecho óbito/DBP36sem. Conclusão Em RN com PCA, a abordagem conservadora relacionou-se à maior mortalidade, a cirúrgica à ocorrência de DBP36s e ROPcir., enquanto o tratamento farmacológico mostrou-se protetor para o desfecho óbito/DBP36sem. Objective: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. Methods: This was a multicentric, cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 – conservative approach (without treatment), G2 – pharmacologic (indomethacin or ibuprofen), G3 – surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. Results: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. Conclusion: The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks. Universidade de São Paulo Faculdade de Medicina Universidade de São Paulo Faculdade de Medicina Department of Pediatrics Universidade Federal do Rio Grande do Sul Faculdade de Medicina Department of Pediatrics and Child Care Universidade Estadual de Campinas Faculdade Ciências Médicas Department of Pediatrics Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Department of Pediatrics Universidade Estadual Paulista Faculdade de Medicina de Botucatu Department of Pediatrics Instituto Fernandes Figueira Fundação Oswaldo Cruz (FIOCRUZ) Department of Neonatology Pontifícia Universidade Católica do Rio Grande do Sul Faculdade de Medicina Department of Pediatrics Universidade Estadual de Londrina Faculdade de Medicina Instituto de Medicina Integral Prof. Fernando Figueira Universidade Federal do Paraná Department of Pediatrics Universidade Federal de Uberlândia Universidade Estadual do Rio de Janeiro Universidade Federal do Maranhão Universidade Federal de Minas Gerais Faculdade de Ciências Médicas de Minas Gerais Universidade Estadual Paulista Faculdade de Medicina de Botucatu Department of Pediatrics

Focal rTMS in Alzheimer’s disease (AD) revealed cognitive benefits. H-coil can depolarize deeper and wider structures compared with focal coils, thus targeting widespread networks involved in neurodegenerative disorders. We aimed to evaluate H-coil rTMS safety and efficacy in AD. Thirty AD subjects (70.21 ± 8.66 y.o.), randomized in real or sham groups, underwent 16 rTMS sessions (3 weekly for 4 weeks, 1 weekly for other 4 weeks), over fronto-parieto-temporal lobes at 10 Hz. Neuropsychological assessment was performed at baseline, after 4 weeks (4w), at the end of treatment (8w). Primary outcome was an improvement in Alzheimer’s disease scale-cognitive (ADAS-cog). No serious side effects were reported. Four subjects were excluded (1 acute myocardial infarction in the sham group, 1 misdiagnosis, 2 missing data), thus statistical analysis included 26 subjects. At 4w, percent ADAS-cog improvement from baseline (4 w%) was greater in the real compared with the sham group (p = 0.042). The relationship between baseline ADAS-cog and 4 w% differed between the two groups (p = 0.009), with higher improvement for less cognitively impaired subjects at baseline only in the real. These findings suggest that H-coil may be safe and effective in AD and that deep rTMS may better impact the course of the disease when administered at earlier stages.

To evaluate the role of optical coherence tomography (OCT) and visual evoked potentials (VEPs) in patients with multiple sclerosis (MS). Study of 121 consecutive subjects with MS. Of 242 eyes, 166 had no previous history of optic neuritis (ON), 22 had a single recent ON episode (3 months before). All patients underwent assessment of EDSS, OCT retinal nerve fiber layer (RNFL) thickness and VEP. 77 subjects underwent to a second EDSS (EDSS2) evaluation after a mean time of 1, 94 years. In eyes with recent ON, the sensitivity of OCT was 38.9% with a higher sensitivity of VEP (77.3%; McNemar p

Background Three variants of primary progressive aphasia (PPA) have been currently characterized: non fluent/agrammatic (nfv-PPA), semantic (sv-PPA), and logopenic variant (lv-PPA). lv-PPA is most commonly associated with Alzheimer's disease (AD), while nfv-PPA and sv-PPA are related to frontotemporal lobar degeneration. Objective We aimed to determine whether cerebrospinal fluid (CSF) amyloid-β42 (Aβ42), total tau protein (t-tau), and phosphorylated tau (p-tau), frequently abnormal in AD, could constitute a useful tool in the PPA diagnostic work up, in order to identify subjects with an underlying AD pathology. Methods We measured CSF biomarker levels in a group of twenty-eight patients, fourteen lv-PPA, nine nfv-PPA, and five sv-PPA. Results Since there were no significant differences in any of the parameters investigated between nfv-PPA and sv-PPA, the two groups were considered as one (nfv/sv-PPA). At diagnosis, lv-PPA were older than nfv/sv-PPA patients (mean values: 70.7 versus 64.6 years, p = 0.02). CSF biomarker mean concentrations were significantly different in lv-PPA versus nfv/sv-PPA patients (p = 0.000): Aβ42 350.64 versus 661.64 ng/L; tau 631.21 versus 232.71 ng/L; p-tau 101 versus 38.21 ng/L. According to the recent AD diagnostic criteria, (Cummings et al., 2013) eleven lv-PPA and only one nfv/sv-PPA showed a liquoral pattern typical for AD. Finally lv-PPA had CSF biomarker levels very similar to a sample of 72 AD patients from our Department. Conclusions Our data showed that CSF biomarkers can easily and reliably detect those patients with language disorders due to an underlying AD pathology, thus offering the possibility of targeted therapeutic interventions. However, because of the small sample size, such analyses should be reproduced in larger populations of patients to confirm our data.

We characterized the functional consequences of intravesical bacillus Calmette-Guérin on the molecular mechanism of the AKT/mTOR signaling pathway in nonmuscle invasive bladder cancer. To our knowledge this has not been reported previously.At age 7 weeks female Fischer 344 rats received 1.5 mg/kg MNU intravesically every other week for 6 weeks. They were randomized at 10 per group to MNU (0.2 ml vehicle), bacillus Calmette-Guérin (10(6) cfu Connaught strain), rapamycin (15 μg/ml) and bacillus Calmette-Guérin plus simultaneous rapamycin, each intravesically for 6 weeks. At week 15 the bladders were collected for histopathology, immunohistochemistry and immunoblot to determine p-AKT, Rictor, Raptor, p-4E-BP1, p-p70S6K1, p-AMPK-α, p-mTOR and p-p53.Papillary carcinoma (pTa) and high grade intraepithelial neoplasia (pTis) predominated in the MNU group while normal urothelium, papillary and flat hyperplasia were more common in treated groups. Nonmuscle invasive bladder cancer treated with bacillus Calmette-Guérin showed suppression of p70S6K1 but not 4E-BP1 phosphorylation. This suggests that 4E-BP1 is regulated differently than p70S6K1, escaping the bacillus Calmette-Guérin action that occurs in a mTOR independent manner. The association of bacillus Calmette-Guérin with rapamycin but not rapamycin monotherapy affected p70S6K1 and 4E-BP1 phosphorylation with no features of in situ carcinoma (pTis).The activation status of p70S6K1 and 4E-BP1 might be used to stratify patients who could benefit from targeting such molecular elements with multitarget/multidrug intravesical therapy. In the future 4E-BP1 might be a worthwhile new target for bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer.

We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010-2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1-10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.

Objective: To assess the sensitivity of optic coherence tomography (OCT) and visual evoked potentials (VEPs) to visual pathway abnormalities in multiple sclerosis (MS). Methods: A total of 40 MS subjects, 28 with optic neuritis (ON) at least 3 months before (bilateral in 5), underwent assessment of visual acuity, Expanded Disability Status Scale (EDSS), OCT and VEPs, the latter quantified with a 0–4 conventional score. Results: OCT and VEPs were abnormal in 36% and 56% respectively in all eyes ( p=0.11), 68% and 86% in eyes with previous ON ( p=0.12), and in 19% versus 40% in eyes without ON history ( p=0.007). Combining VEP and OCT increased sensitivity to 89% in ON and 44% in non-ON eyes. Considering all eyes, global retinal nerve fibre layer (RNFL) thickness and VEP score were significantly correlated between them (ρ=−0.63, pConclusions: In eyes without ON, VEPs were more frequently abnormal than OCT, while the two techniques showed similar sensitivity in eyes previously affected by ON. The correlation of VEPs and OCT measures with disability prompts further exploration of the two techniques as potential markers of disease burden.

The authors report a case of subdural haematoma (HSD), which occurred following epidural analgesia for labour, complicated by post dural puncture headache (PDPH). A 26-year-old woman displayed a typical PDPH following epidural anaesthesia. On the sixth day, she was given a blood patch (BP), which was partially efficacious. Because of worsening of the headache, of disappearance of the postural characteristics, and of vomiting without focal neurological signs on the 9th day, a CT-scan was done. The CT-scan showed a small hemispheric subdural haematoma. The recovery was complete with only medical treatment. HSD is a rare serious complication of dural puncture. When the characteristics of PDPH change, HSD should be evoked even without focal neurological signs. An early diagnosis and the small size of the haematoma may allow HSD to be treated medically and avoid surgical evacuation.