Geriatric screening and comprehensive geriatric assessment during initial oncology appointments.

INTRODUCTION: Geriatric oncology underscores the significance of assessing functional age in guiding medical decisions, endeavouring to delineate practical and efficacious methodologies for evaluating functionality, adapting therapeutic regimens and attenuating the risks of treatment-related deterioration. OBJECTIVES AND METHODS: In this prospective study, we aimed to delineate the characteristics of older patients presenting for their initial oncology appointment by using geriatric screening (G8 score) and comprehensive geriatric assessment (CGA), while also assessing the feasibility of these evaluations. Secondary objectives included comparing the initial Eastern Cooperative Oncology Group (ECOG) performance status and any deviations from standard therapeutic strategies against the identified frailty in geriatric assessment. RESULTS: Most patients exhibited a G8 score ≤14 and underwent comprehensive geriatric assessment. While oncologists typically perceive patients' general conditions, CGA enables a systematic assessment, providing a comprehensive characterisation of elderly patients to inform therapeutic decisions and address identified fragilities. The CGA highlighted vulnerabilities across all primary domains. Notably, even among patients with ECOG scores of 0 and 1, the application of G8 score and CGA revealed numerous fragilities. Consistent with existing literature, these scales offered additional insights beyond ECOG evaluation alone, suggesting their potential to guide therapeutic adaptations for this demographic. CONCLUSION: Ongoing research and continuous evaluation are imperative to refine and broaden the implementation of geriatric-focused interventions.

Second-look upper endoscopy as the initial approach to subepithelial lesions: a reassuring and reliable strategy.

BACKGROUND: Although endoscopic ultrasound (EUS) plays a critical role in the management of subepithelial lesions (SEL) of upper gastrointestinal tract many can be classified solely by a thorough upper gastrointestinal endoscopy (UGE) which can reduce the burden of additional studies. AIMS: Analyze the impact of a stepwise approach starting with a second-look UGE before the decision of EUS in patients referred to our center with suspected SEL. METHODS: Retrospective cohort study which included all adult patients referred to our center between 2015 and 2020 with suspected SEL.Second-look UGE evaluated the location, size, color, surface characteristics, movability and consistency of the SEL and bite-on-bite biopsies were performed. Decisions on SEL management and follow-up were collected. RESULTS: A total of 193 SEL (190 patients) were included. At the index-UGE, stomach was the most frequent location (n = 115;59.6%). Most patients performed a second-look UGE (n = 180; 94.7%). A minority was oriented directly to EUS (n = 8;4.2%) or endoscopic resection (n = 2; 1.1%). In patients who underwent a second-look UGE, SEL were excluded in 25 (13.9%) and 21 (11.7%) did not need further work-up. The remaining patients were submitted to EUS (n = 88;48.9%), surveillance by UGE (n = 44; 24.4%) or endoscopic resection (n = 2; 1.1%). CONCLUSION: Systematically performing a second-look UGE, in patients referred with suspected SEL, safely preclude the need for subsequent investigation in approximately one-fourth of the patients. As UGE is less invasive and more readily available, we suggest that a second-look UGE should be the initial approach in SEL management.

Visualizing the target estimand in comparative effectiveness studies with multiple treatments.

Aim: Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bias. We show that corresponding treatment effect estimates may have limited external validity, and propose two visualization tools to clarify the target estimand. Materials & methods: We conduct a simulation study to demonstrate, with bivariate ellipses and joy plots, that differences in covariate distributions across treatment groups may affect the external validity of treatment effect estimates. We showcase how these visualization tools can facilitate the interpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF) and natalizumab (NAT) on manual dexterity in patients with multiple sclerosis. Results: In the simulation study, estimates of the treatment effect greatly differed depending on the target population. For example, when comparing treatment B with C, the estimated treatment effect (and respective standard error) varied from -0.27 (0.03) to -0.37 (0.04) in the type of patients initially receiving treatment B and C, respectively. Visualization of the matched samples revealed that covariate distributions vary for each comparison and cannot be used to target one common treatment effect for the three treatment comparisons. In the case study, the bivariate distribution of age and disease duration varied across the population of patients receiving TERI, DMF or NAT. Although results suggest that DMF and NAT improve manual dexterity at 1 year compared with TERI, the effectiveness of DMF versus NAT differs depending on which target estimand is used. Conclusion: Visualization tools may help to clarify the target population in comparative effectiveness studies and resolve ambiguity about the interpretation of estimated treatment effects.

Gastric dysplasia in random biopsies: the influence of Helicobacter pylori infection and alcohol consumption in the presence of a lesion.

BACKGROUND: Gastric dysplasia in the absence of an endoscopically defined lesion is rare, usually either a false positive diagnosis or a previously unidentified precancerous lesion during esophagogastroduodenoscopy (EGD). AIMS: Evaluate factors associated with the presence of an endoscopically visible lesion during follow-up in patients with histologic diagnosis of gastric dysplasia in random biopsies. METHODS: Retrospective cohort study including patients referred to our institution for gastric dysplasia in random biopsies during Index EGD. Endoscopic evaluation was performed with a high-definition endoscope using narrow band imaging (HD EGD-0). If no lesion was detected, endoscopic surveillance (HD EGD-FU) was conducted within 6 months for high grade dysplasia (HGD) or 12 months for low grade (LGD) or indefinite for dysplasia (IFD). RESULTS: From a total sample of 96 patients, 5 (5.2%) presented with an endoscopically visible lesion during HD EGD-0, while 10 lesions (10.4%) were identified during HD EGD-FU. Patients with Helicobacter pylori infection at Index EDG and with regular alcohol consumption (≥25 g/day) were 8 and 4 times more likely to have an endoscopically visible lesion on HD EGD-FU (p = 0.012 and p = 0.047). In binary logistic regression, both factors were independent predictors of the presence of gastric lesion on HD EGD-FU (OR 9.284, p = 0.009 and OR 5.025, p = 0.033). CONCLUSIONS: The presence of an endoscopically visible lesion after the histologic diagnosis of gastric dysplasia in random biopsies was more frequent during HD EGD-FU. H. pylori infection at Index EGD and regular alcohol consumption were significant predictors of the presence of gastric lesion on HD EGD-FU.

Identifying inflammatory bowel disease patients at risk of metabolic dysfunction-associated fatty liver disease: usefulness of non-invasive steatosis predictive scores.

BACKGROUND: Inflammatory bowel disease (IBD) patients have a higher risk of metabolic dysfunction-associated fatty liver disease (MAFLD) compared with the general population. However, it is not known whether available non-invasive hepatic steatosis scores are useful in predicting MAFLD in IBD patients. We aimed to analyze the performances of MAFLD screening score (MAFLD-S), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Clinical Prediction Tool for NAFLD in Crohn's Disease (CPN-CD), in identifying MAFLD in IBD patients. METHODS: A cross-sectional study was carried out including consecutive adult IBD outpatients submitted to transient elastography (TE). MAFLD criteria were assessed, and hepatic steatosis (HS) was defined by a controlled attenuation parameter (CAP) >248 dB/m using TE. MAFLD-S, FLI, HSI, and CPN-CD were calculated and their accuracy for the prediction of MAFLD was evaluated through their areas under the receiver-operating characteristic (AUROC) curves. RESULTS: Of 168 patients, body mass index ≥25, type 2 diabetes mellitus, dyslipidemia and arterial hypertension were present in 76 (45.2%), 10 (6.0%), 53 (31.5%), 20 (11.9%), respectively. HS was identified in 77 (45.8%) patients, of which 65 (84.4%) fulfilled MAFLD criteria. MAFLD-S (AUROC, 0.929 [95% CI, 0.888-0.971]) had outstanding and FLI (AUROC, 0.882 [95% CI, 0.830-0.934]), HSI (AUROC, 0.803 [95% CI, 0.736-0.871]), and CPN-CD (AUROC, 0.822 [95% CI, 0.753-0.890) had excellent discrimination in predicting MAFLD. CONCLUSIONS: MAFLD-S, FLI, HSI and CPN-CD scores can accurately identify MAFLD in IBD patients, allowing the selection of those in whom hepatic steatosis and metabolic risk factors assessment may be particularly beneficial.

Adjuvant Hyperthermic Intravesical Chemotherapy in Intermediate- and High-Risk Non-muscle Invasive Bladder Cancer.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a frequently diagnosed neoplasm, which is typically managed with transurethral resection of bladder tumor (TURBT) eventually followed by intravesical therapies. Bacillus Calmette-Guérin (BCG) is used as first-line adjuvant treatment in high- (HR) and intermediate-risk (IR) NMIBC, although, in the latter, mitomycin C (MMC) may also be used. Multiple limitations to the use of BCG encouraged the search for therapeutic alternatives. In this context, hyperthermic intravesical chemotherapy with MMC (HIVEC-MMC) emerged as a promising therapy in the adjuvant setting for NMIBC. The aim of our study was to evaluate the tolerability, compliance, and survival outcomes of HIVEC-MMC in patients with IR- and HR-NMIBC. MATERIAL AND METHODS: This was a single-center retrospective analysis of IR- and HR- NMIBC patients who received HIVEC-MMC after TURBT between August 2018 and August 2022. Levels of risk stratification were defined using the European Association of Urology (EAU) criteria. The protocol consisted of four weekly HIVEC-MMC instillations (induction) followed by six monthly instillations (maintenance). The primary outcomes were to evaluate the tolerability and compliance with the HIVEC-MMC protocol and secondary outcomes were disease-free survival (DFS) and overall survival (OS). For the purpose of statistical analysis, methods of descriptive statistics, survival analysis (Kaplan-Meier estimation), and multivariate analysis (Cox regression, and binary logistic regression) were used. RESULTS: Fifty-seven patients were enrolled with a median age of 67.9 (34.4-83.5) years old. In this cohort, 40 patients (70.2%) had primary tumors. At the time of referral for HIVEC-MMC, the majority of the patients had IR-NMIBC (n= 33, 57.9%). A total of 41 patients (71.9%) completed the HIVEC-MMC protocol. Disease recurrence and adverse events (AEs) were the most common reasons to stop the protocol. After a median follow-up of 31 months (95% CI, 5.0-54.0), 32 patients (61.4%) were disease-free, 22 (38.6%) experienced recurrent disease and six patients (10.5%) died, although only one death was directly attributable to bladder cancer. The median DFS was 42 months (95% CI, 28.0-56.0). Completion of the HIVEC-MMC maintenance phase protocol stood as a predictive factor for DFS (44 months, 95% CI 29.1-58.9 vs. 14 months, 95% CI 0.0-29.6, p < 0.001; HR 4.48, 95% CI 1.65-12.15). The median OS was not reached; the 24- and 48-month OS were 92.6% and 82.7%, respectively. EAU risk group, ECOG-PS, and completion of HIVEC protocol were found to be significant predictive factors of OS but lost their significance on multivariate analysis. However, if we exclude those who experienced recurrence during the maintenance phase protocol, treatment completion had a significant positive impact on OS (HR: 42.8, 95% CI 1.75-1045.072, p= 0.021). CONCLUSIONS: Our study suggests that HIVEC is a secure and well-tolerated treatment with promising efficacy data, making this therapeutic approach a feasible option in IR- and HR-NMIBC patients, mainly in those who cannot tolerate or have contraindications to BCG therapy, but also as an alternative during BCG shortages.

"Grey areas" in large rectal neuroendocrine tumors: when endoscopic ultrasound becomes the silver lining.

A 50-years old male with irrelevant medical history underwent colonoscopy for colorectal cancer screening. On the distal rectum, a subpedunculated (Paris classification Isp) lesion with 15mm was detected. This lesion presented yellowish mucosa and had irregular surfaces, suggesting a subepithelial lesion. Bite-on-bite biopsy confirmed a well-differentiated neuroendocrine tumor (r-NET), positive for synaptophysin, with a low-proliferative index. As r-NETs with 10-20mm fall on a grey area between endoscopic or surgical treatment, a lower endoscopic ultrasound (EUS) was performed, showing a round hypoechoic "salt and pepper" lesion of the mucosa, with focal involvement of the submucosa (3rd layer), but without muscularis propria invasion or regional lymph node involvement (uT1N0). No distal metastases were detected on computed tomography. Thus, the patient was proposed for endoscopic submucosal dissection. With this case we aim to recall EUS importance in large r-NETs, as adequate staging is crucial when deciding optimal therapeutic options.

HER2 Status in RAS and BRAF Wild-Type Metastatic Colorectal Cancer: A Portuguese Study.

INTRODUCTION: Colorectal cancer (CRC) is the second-most deadly cancer worldwide. However, there remains a scarcity of precision treatments available for this type of cancer. Amplification or overexpression of human epidermal growth factor receptor 2 (HER2+) is a well-established therapeutic target in gastric and breast cancer. HER2 is positive in approximately 5% of CRC cases and has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies. The aim of this study was to evaluate HER2 status in RAS and BRAF wild-type metastatic CRC (mCRC) and its correlation with survival outcomes. MATERIALS AND METHODS: A single-center retrospective analysis of RAS and BRAF wild-type mCRC patients undergoing systemic treatment was conducted from July 2014 to September 2020. Tissue HER2 status was determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) and/or chromogenic in situ hybridization (CISH). HER2+ was defined as IHC3 (+) or IHC2 (+) through FISH or CISH (+). RESULTS: Fifty-nine patients were included. The median age of all the included patients was 64 years (33-82). Four patients had HER2+ tumors (7%). Four patients had HER2+ tumors (7%). The majority of HER2+ mCRC cases were males (n=3) and left-sided CRC (n=3). All patients received FOLFIRI plus cetuximab as first-line treatment. At the median follow-up of 24.0 months, patients with HER2-negative mCRC presented with a median overall survival (mOS) of 39.4 months (95% confidence interval (CI) 32.7-46.0) and the four patients with HER2+ mCRC had a mOS of 20.4 months (95% CI; 9.5-31.3; p=0.07). In HER2-negative patients, the median PFS (mPFS) was 11.3 months (95% CI; 9.2-13.4) vsHER2-positive patients with a mPFS of 10.9 months (95% CI; 1.3-20.4; p=0.47). CONCLUSIONS: To our knowledge, this is the first study reporting HER2+ in mCRC patients in a Portuguese population and the HER2+ rate was consistent with previous studies. Our study suggests that HER2+ may potentially be a marker that is able to predict poor prognosis in RAS and BRAF wild-type mCRC.

Development and validation of a machine learning-supported strategy of patient selection for osteoarthritis clinical trials: the IMI-APPROACH study.

Objectives: To efficiently assess the disease-modifying potential of new osteoarthritis treatments, clinical trials need progression-enriched patient populations. To assess whether the application of machine learning results in patient selection enrichment, we developed a machine learning recruitment strategy targeting progressive patients and validated it in the IMI-APPROACH knee osteoarthritis prospective study. Design: We designed a two-stage recruitment process supported by machine learning models trained to rank candidates by the likelihood of progression. First stage models used data from pre-existing cohorts to select patients for a screening visit. The second stage model used screening data to inform the final inclusion. The effectiveness of this process was evaluated using the actual 24-month progression. Results: From 3500 candidate patients, 433 with knee osteoarthritis were screened, 297 were enrolled, and 247 completed the 2-year follow-up visit. We observed progression related to pain (P, 30%), structure (S, 13%), and combined pain and structure (P â€‹+ â€‹S, 5%), and a proportion of non-progressors (N, 52%) ∼15% lower vs an unenriched population. Our model predicted these outcomes with AUC of 0.86 [95% CI, 0.81-0.90] for pain-related progression and AUC of 0.61 [95% CI, 0.52-0.70] for structure-related progression. Progressors were ranked higher than non-progressors for P â€‹+ â€‹S (median rank 65 vs 143, AUC = 0.75), P (median rank 77 vs 143, AUC = 0.71), and S patients (median rank 107 vs 143, AUC = 0.57). Conclusions: The machine learning-supported recruitment resulted in enriched selection of progressive patients. Further research is needed to improve structural progression prediction and assess this strategy in an interventional trial.

Ageing in the brain: mechanisms and rejuvenating strategies.

Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism's fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. With the rise in life expectancy, characterizing the brain ageing process becomes fundamental for developing therapeutic interventions against the increased incidence of age-related neurodegenerative diseases and to aim for an increase in human life span and, more importantly, health span. In this review, we start by introducing the molecular/cellular hallmarks associated with brain ageing and their impact on brain cell populations. Subsequently, we assess emerging evidence on how systemic ageing translates into brain ageing. Finally, we revisit the mainstream and the novel rejuvenating strategies, discussing the most successful ones in delaying brain ageing and related diseases.

Nanoparticles as a Delivery System of Antigens for the Development of an Effective Vaccine against Toxoplasma gondii.

Nanoparticles include particles ranging in size from nanometers to micrometers, whose physicochemical characteristics are optimized to make them appropriate delivery vehicles for drugs or immunogens important in the fight and/or prevention of infectious diseases. There has been a rise in the use of nanoparticles in preventive vaccine formulations as immunostimulatory adjuvants, and as vehicles for immunogen delivery to target immune cells. Toxoplasma is important worldwide, and may cause human toxoplasmosis. In immunocompetent hosts, infection is usually asymptomatic, but in immunocompromised patients it can cause serious neurological and ocular consequences, such as encephalitis and retinochoroiditis. Primary infection during pregnancy may cause abortion or congenital toxoplasmosis. Currently, there is no effective human vaccine against this disease. Evidence has emerged from several experimental studies testing nanovaccines showing them to be promising tools in the prevention of experimental toxoplasmosis. For the present study, a literature review was carried out on articles published over the last 10 years through the PubMed database, pertaining to in vivo experimental models of T. gondii infection where nanovaccines were tested and protection and immune responses evaluated. This review aims to highlight the way forward in the search for an effective vaccine for toxoplasmosis.

Peripheral Nerve Block Practice in Portugal: A National Survey.

Regional anesthesia (RA) has several benefits and its use has increased with the advent of ultrasound-guided techniques. Opioid-sparing anesthesia and reduced use of general anesthesia are some of the mainstay advantages of RA. Although anesthetic practices differ deeply between countries, RA has assumed a crucial role in the daily practice of anesthesiologists, particularly during the COVID-19 pandemic period. This cross-sectional study provides an overview of peripheral nerve block (PNB) techniques performed in Portuguese hospitals. An online survey was reviewed by members of Clube de Anestesia Regional (CAR/ESRA Portugal) and then sent to a national mailing list of anesthesiologists. The survey focused on specific topics related to RA techniques such as the importance of training and experience, and the relevance of logistical limitations during the execution of RA. All data were collected anonymously and included in a Microsoft Excel (Microsoft Corp., Redmond, WA, USA) database, for further analysis. A total of 335 valid answers were obtained. All participants considered RA as a key competence in their daily practice. Half of those inquired performed PNB techniques once to twice per week. The main limitations identified for performing RA in Portuguese hospitals were the absence of block rooms and insufficiently trained personnel for the appropriate and safe execution of these techniques. This survey provides a comprehensive overview of RA in the Portuguese setting and could serve as a baseline for further studies.

Oral Hygiene in Patients with Stroke: A Best Practice Implementation Project Protocol.

Oral hygiene has been shown to reduce adverse events and promote the quality of life of patients with stroke. However, a stroke can result in the impairment of physical, sensory, and cognitive abilities, and comprise self-care. Although nurses recognize its benefits, there are areas for improvement in the implementation of the best evidence-based recommendations. The aim is to promote compliance with the best evidence-based recommendations on oral hygiene in patients with stroke. This project will follow the JBI Evidence Implementation approach. The JBI Practical Application of Clinical Evidence System (JBI PACES) and the Getting Research into Practice (GRiP) audit and feedback tool will be used. The implementation process will be divided into three phases: (i) establishing a project team and undertaking the baseline audit; (ii) providing feedback to the healthcare team, identifying barriers to the implementation of best practices, and co-designing and implementing strategies using GRIP, and (iii) undertaking a follow-up audit to assess the outcomes and plan for sustainability. So, the successful adoption of the best evidence-based recommendations on oral hygiene in patients with stroke will reduce the adverse events related to poor oral care and may improve patients' quality of care. This implementation project has great transferability potential to other contexts.

A "new" option in Helicobacter pylori eradication: High-dose amoxicillin dual therapy outperforms bismuth quadruple therapy in a high dual resistance setting.

BACKGROUND: Currently, bismuth quadruple therapy (BQT) is indicated as a first-line treatment for Helicobacter pylori eradication in areas with high dual metronidazole and clarithromycin resistance, with its use being limited by its low tolerability and significant cost. A novel regimen with high-dose amoxicillin dual therapy (HDADT) has emerged as an alternative. The aim of this study was to compare the results of these two treatments on HP eradication. MATERIALS AND METHODS: Prospective randomized study including 100 consecutive patients undergoing H. pylori eradication. Each patient was randomized (in a 1:1 ratio) to one group of treatment: BQT (bismuth 140 mg + metronidazole 125 mg + tetracycline 125 mg, four times a day, for 10 days) or HDADT (amoxicillin 1000 mg alternating with amoxicillin 500 mg, four times a day, for 14 days), both associated with esomeprazole 40 mg twice a day. The primary aim was to compare treatments' efficacies. Secondary aims were to assess symptoms persistence and tolerability. RESULTS: A total of 100 patients were included, 54% women, with a mean age of 55 ± 14 years. From these, five were lost to follow-up. Effective eradication proven by negative stool antigen test was significantly higher in patients randomized to HDADT when compared to BQT for both intention-to-treat (ITT) (96.2% vs. 81.4%; p = .022) and per-protocol (PP) (95.9% vs. 81%; p = .025) analysis. These differences were even more pronounced when only considering second line treatment (100% vs. 62.5%; p = .028). Side effects did not differ significantly between BQT and HDADT groups for both ITT (7.0% vs. 2.0%; p = .254) and PP (4.8% vs. 0%; p = .210) analysis. CONCLUSIONS: When compared to BQT, treatment with HDADT presented higher and near 100% efficacy in eradicating H. pylori, without differences in reported side effects or compliance. This treatment represents an important alternative for populations with increasing incidences of resistance to the currently recommended antibiotic regimens.

The New FibroScan-AST (FAST) Score: Enhancing Diabetes Mellitus Impact on Metabolic-Associated Fatty Liver Disease.

Background: Metabolic-associated fatty liver disease (MAFLD) is an increasingly prevalent cause of chronic liver disease. In 2020, the FibroScan-AST (FAST) score was internationally validated as a new tool able to identify patients with steatohepatitis who benefit the most from further therapies, based on liver transient elastography (LTE) findings and serum levels of aspartate aminotransferase (AST). We aimed to identify, in MAFLD patients, which metabolic features may predict a higher FAST score. Methods: Retrospective study of consecutive patients with MAFLD submitted to LTE for two consecutive years. Patients without an AST sample collected within 6 months of the LTE were excluded. FAST score was calculated, stratifying the patient's risk as low (<0.35), medium (0.35-0.67), or high (>0.67). Results: The sample included 117 patients, 53.0% of the female gender, with a mean age of 53 years. On multivariate analysis, patients with type 2 diabetes (T2DM) (p < 0.001), dyslipidemia (p = 0.046), and smoking habits (p = 0.037) presented with significantly higher FAST score values. Furthermore, diabetic patients did not only present significantly higher FAST scores but were also more frequently assigned to the high-risk group according to FAST score criteria (OR = 9.2; 95% CI = 1.8-45.5; p = 0.007). Conclusions: Calculating the FAST score, patients with T2DM presented a significantly higher risk of having significant fibrosis and steatohepatitis. Physicians may rely on this validated instrument to more easily identify which patients with T2DM and MAFLD benefit the most from a specialized follow-up.

Introdução: O figado gordo associado a disfuncao metabolica (FGADM) e uma causa crescente de doenca hepatica cronica. Em 2020, o score Fibroscan-AST (FAST) foi validado internacionalmente como uma nova ferramenta capaz de identificar pacientes com esteatohepatite que beneficiam de terapeuticas adicionais, baseado nos achados da elastografia hepatica transitoria (EHT) e niveis sericos de aspartato aminotransferase (AST). Os autores procuraram identificar, em pacientes com FGADM, que fatores metabolicos predizem um score-FAST maior. Métodos: Estudo retrospetivo de pacientes com FGADM submetidos a EHT durante 2 anos consecutivos. Pacientes sem uma amostra de AST colhida nos 6 meses previos a EHT foram excluidos. O score-FAST foi calculado, estratificando o risco do paciente como baixo (<0,35), moderado (0,35-0,67) ou alto (>0,67). Resultados: A amostra incluiu 117 pacientes, 53% do sexo feminino, com uma idade media de 53 anos. Em analise multivariada, pacientes com Diabetes Mellitus tipo 2 (DMT2) (p < 0,001), dislipidemia (p = 0,046) e habitos tabagicos (p = 0,037) apresentaram valores de score-FAST significativamente maiores. Alem disso, os pacientes diabeticos apresentaram nao so valores de score-FAST significativamente maiores, como tambem foram mais frequente classificados como pertencendo ao grupo de alto risco, de acordo com os criterios deste score (OR = 9,2; 95%IC = 1,8­45,5; p = 0,007). Conclusões: Calculando o score-FAST, pacientes com FGADM e DMT2 apresentaram um risco significativamente maior. Esta ferramenta validada podera ser utilizada para selecionar os pacientes com DMT2 e FGADM que poderao beneficiar de seguimento especializado.

End-of-Life Antibiotherapy: Factors Associated With Prescription.

Introduction Most cancer patients spend their last days of life in the hospital, often receiving invasive and non-palliative interventions. These patients are particularly susceptible to infections, which are a major cause of death. The decision to use antimicrobials in a palliative context is difficult, given the lack of guidelines. Objectives To characterize patients who received antimicrobials at the end of life and analyze factors associated with their prescription decisions. Methods A retrospective analysis of patients who died in the Medical Oncology Service from January to December 2017 was done. In addition, the use of antibiotics in the last 15 days of life was considered. Clinical, therapeutic, and Eastern Corporative Oncology Group Performance Status Scale (ECOG PS) variables were analyzed using SPSS v23. Results There were a total of 116 deaths, of which 48.3% (n = 56) received antimicrobials in their last 15 days of life. The median age of the patients was 64.5 years. Most patients (55.4%) had an ECOG PS 4, of which 82.1% were stage IV tumors. The most frequent tumors were colorectal adenocarcinomas (21.3%), digestive non-colorectal (predominantly gastric or esophageal adenocarcinomas) (20.5%), and invasive breast carcinomas (16.4%). Asthenia (33.6%) and dyspnea (19.8%) were the main complaints, and most patients (55.4%) had respiratory infections. Fever was present in 51.8% of patients on antibiotics and was related to their use (p < 0.001). The use of antimicrobials is also related to higher C-reactive protein (CRP) values (p = 0.015). Conclusions The decision to institute antimicrobials at the end of life is related to clinical and analytical aspects suggestive of infection without considering the patient's general condition and the oncological disease's prognosis. Deprescription of antibiotic therapy is not yet a current clinical practice.

Epigallocatechin-3-gallate Delivered in Nanoparticles Increases Cytotoxicity in Three Breast Carcinoma Cell Lines.

The anticancer activity of epigallocatechin-3-gallate (EGCG), orally administrated, is limited by poor bioavailability, absorption, and unpredictable distribution in human tissues. EGCG charged nanoparticles may represent an opportunity to overcome these limitations. We assayed two different kinds of lipid nanoparticles (LNPs and LNPs functionalized with folic acid) charged with EGCG on three breast carcinoma cell lines (MCF-7, MDA-MB-231, and MCF-7TAM) and the human normal MCF10A mammary epithelial cells. Both LNPs loaded with EGCG, at low concentrations, induced a significant cytotoxicity in the three breast carcinoma cells but not in MCF10A cells. In view of a future application, both LNPs and LNPs-FA were found to be very suitable for in vitro studies and useful to improve EGCG administration in vivo. Since they are produced by inexpensive procedures using bioavailable, biocompatible, and biodegradable molecules, they represent an applicable tool for a more rationale use of EGCG as an anti-cancer agent.

Adenosine A2A receptors control synaptic remodeling in the adult brain.

The molecular mechanisms underlying circuit re-wiring in the mature brain remains ill-defined. An eloquent example of adult circuit remodelling is the hippocampal mossy fiber (MF) sprouting found in diseases such as temporal lobe epilepsy. The molecular determinants underlying this retrograde re-wiring remain unclear. This may involve signaling system(s) controlling axon specification/growth during neurodevelopment reactivated during epileptogenesis. Since adenosine A2A receptors (A2AR) control axon formation/outgrowth and synapse stabilization during development, we now examined the contribution of A2AR to MF sprouting. A2AR blockade significantly attenuated status epilepticus(SE)-induced MF sprouting in a rat pilocarpine model. This involves A2AR located in dentate granule cells since their knockdown selectively in dentate granule cells reduced MF sprouting, most likely through the ability of A2AR to induce the formation/outgrowth of abnormal secondary axons found in rat hippocampal neurons. These A2AR should be activated by extracellular ATP-derived adenosine since a similar prevention/attenuation of SE-induced hippocampal MF sprouting was observed in CD73 knockout mice. These findings demonstrate that A2AR contribute to epilepsy-related MF sprouting, most likely through the reactivation of the ability of A2AR to control axon formation/outgrowth observed during neurodevelopment. These results frame the CD73-A2AR axis as a regulator of circuit remodeling in the mature brain.