Haemostatic gene variations in cervical cancer-associated venous thrombosis: considerations for clinical strategies.

Venous thromboembolism (VTE) is a life-threatening haemostatic disease frequently diagnosed among the cancer population. The Khorana Score is currently the primal risk assessment model to stratify oncological patients according to their susceptibility to VTE, however, it displays a limited performance. Meanwhile, intensive research on VTE pathophysiology in the general population has uncovered a range of single-nucleotide polymorphisms (SNPs) associated with the condition. Nonetheless, their predictive ability concerning cancer-associated thrombosis (CAT) is controversial. Cervical cancer (CC) patients undergoing chemoradiotherapy often experience VTE, which negatively affects their survival. Thus, aiming for an improvement in thromboprophylaxis, new thrombotic biomarkers, including SNPs, are currently under investigation. In this study, the predictive capability of haemostatic gene SNPs on CC-related VTE and their prognostic value regardless of VTE were explored. Six SNPs in haemostatic genes were evaluated. A total of 401 CC patients undergoing chemoradiotherapy were enrolled in a retrospective cohort study. The implications for the time to VTE occurrence and overall survival (OS) were assessed. CAT considerably impacted the CC patients' OS (log-rank test, P < 0.001). SERPINE1 rs2070682 (T > C) showed a significant association with the risk of CC-related VTE (CC/CT vs. TT, log-rank test, P = 0.002; C allele, Cox model, hazard ratio (HR) = 6.99 and P = 0.009), while F2 rs1799963 (G > A) demonstrated an important prognostic value regardless of VTE (AA/AG vs. GG, log-rank test, P = 0.020; A allele, Cox model, HR = 2.76 and P = 0.026). For the remaining SNPs, no significant associations were detected. The polymorphisms SERPINE1 rs2070682 and F2 rs1799963 could be valuable tools in clinical decision-making, aiding in thromboprophylaxis and CC management, respectively.

Primary thromboprophylaxis in cancer outpatients - real-world evidence.

INTRODUCTION: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal. AIMS: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal. METHODS: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death. RESULTS: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542). CONCLUSION: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population.

Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients.

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.

Assessment of cardiovascular physiology using dobutamine stress cardiovascular magnetic resonance reveals impaired contractile reserve in patients with cirrhotic cardiomyopathy.

BACKGROUND: Liver cirrhosis has been shown to affect cardiac performance. However cardiac dysfunction may only be revealed under stress conditions. The value of non-invasive stress tests in diagnosing cirrhotic cardiomyopathy is unclear. We sought to investigate the response to pharmacological stimulation with dobutamine in patients with cirrhosis using cardiovascular magnetic resonance. METHODS: Thirty-six patients and eight controls were scanned using a 1.5 T scanner (Siemens Symphony TIM; Siemens, Erlangen, Germany). Conventional volumetric and feature tracking analysis using dedicated software (CMR42; Circle Cardiovascular Imaging Inc, Calgary, Canada and Diogenes MRI; Tomtec; Germany, respectively) were performed at rest and during low to intermediate dose dobutamine stress. RESULTS: Whilst volumetry based parameters were similar between patients and controls at rest, patients had a smaller increase in cardiac output during stress (p = 0.015). Ejection fraction increase was impaired in patients during 10 µg/kg/min dobutamine as compared to controls (6.9 % vs. 16.5 %, p = 0.007), but not with 20 µg/kg/min (12.1 % vs. 17.6 %, p = 0.12). This was paralleled by an impaired improvement in circumferential strain with low dose (median increase of 14.4 % vs. 30.9 %, p = 0.03), but not with intermediate dose dobutamine (median increase of 29.4 % vs. 33.9 %, p = 0.54). There was an impaired longitudinal strain increase in patients as compared to controls during low (median increase of 6.6 % vs 28.6 %, p < 0.001) and intermediate dose dobutamine (median increase of 2.6%vs, 12.6 % p = 0.016). Radial strain response to dobutamine was similar in patients and controls (p > 0.05). CONCLUSION: Cirrhotic cardiomyopathy is characterized by an impaired cardiac pharmacological response that can be detected with magnetic resonance myocardial stress testing. Deformation analysis parameters may be more sensitive in identifying abnormalities in inotropic response to stress than conventional methods.

Comprehensive look at rectal squamous cell carcinoma.

Rectal squamous cell carcinoma (rSCC) is a rare cancer (0.5% of all rectal cancers). It typically presents at an advanced stage and has a poor prognosis. Recently, chemoradiotherapy with organ preservation has become an option for complete response (CR). Surveillance is essential to prompt recognition of recurrence due to its high risk. We present a case of an elderly woman with rSCC stage cT4N1aM0 who underwent a combination of chemotherapy (mitomycin and fluoropyrimidine) and radiotherapy with CR and organ preservation. The patient has been in follow-up for 2 years with digital rectal examination, tumour markers, pelvic MRI, thoracic and upper abdominal CT, proctoscopy and positron emission tomography, with no disease recurrence. This highlights the success of chemoradiotherapy for rSCC treatment, allowing organ preservation.

Lung ultrasound and diuretic therapy in chronic heart failure: a randomised trial.

BACKGROUND: Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. AIMS: To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. METHODS: Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). RESULTS: A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile25-75) age was 72 (63-82) years, 82 (62%) were men, and the median LVEF was 39 (31-51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07-6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. CONCLUSIONS: Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status.

Haemostatic Gene Expression in Cancer-Related Immunothrombosis: Contribution for Venous Thromboembolism and Ovarian Tumour Behaviour.

Ovarian cancer (OC) is the deadliest gynaecological malignancy. Identifying new prognostic biomarkers is an important research field. Haemostatic components together with leukocytes can drive cancer progression while increasing the susceptibility to venous thromboembolism (VTE) through immunothrombosis. Unravelling the underlying complex interactions offers the prospect of uncovering relevant OC prognostic biomarkers, predictors of cancer-associated thrombosis (CAT), and even potential targets for cancer therapy. Thus, this study evaluated the expression of F3, F5, F8, F13A1, TFPI1, and THBD in peripheral blood cells (PBCs) of 52 OC patients. Those with VTE after tumour diagnosis had a worse overall survival (OS) compared to their counterparts (mean OS of 13.8 ± 4.1 months and 47.9 ± 5.7 months, respectively; log-rank test, p = 0.001). Low pre-chemotherapy F3 and F8 expression levels were associated with a higher susceptibility for OC-related VTE after tumour diagnosis (χ2, p < 0.05). Regardless of thrombogenesis, patients with low baseline F8 expression had a shorter progression-free survival (PFS) than their counterparts (adjusted hazard ratio (aHR) = 2.54; p = 0.021). Among those who were not under platelet anti-aggregation therapy, low F8 levels were also associated with a shorter OS (aHR = 6.16; p = 0.006). Moving forward, efforts should focus on external validation in larger cohorts.

Plasma microRNA Environment Linked to Tissue Factor Pathway and Cancer-Associated Thrombosis: Prognostic Significance in Ovarian Cancer.

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway-miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p-in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.

Advances and Challenges in Cell Biology for Cultured Meat.

Cultured meat is an emerging biotechnology that aims to produce meat from animal cell culture, rather than from the raising and slaughtering of livestock, on environmental and animal welfare grounds. The detailed understanding and accurate manipulation of cell biology are critical to the design of cultured meat bioprocesses. Recent years have seen significant interest in this field, with numerous scientific and commercial breakthroughs. Nevertheless, these technologies remain at a nascent stage, and myriad challenges remain, spanning the entire bioprocess. From a cell biological perspective, these include the identification of suitable starting cell types, tuning of proliferation and differentiation conditions, and optimization of cell-biomaterial interactions to create nutritious, enticing foods. Here, we discuss the key advances and outstanding challenges in cultured meat, with a particular focus on cell biology, and argue that solving the remaining bottlenecks in a cost-effective, scalable fashion will require coordinated, concerted scientific efforts. Success will also require solutions to nonscientific challenges, including regulatory approval, consumer acceptance, and market feasibility. However, if these can be overcome, cultured meat technologies can revolutionize our approach to food.

Acute heart failure - an EFIM guideline critical appraisal and adaptation for internists.

BACKGROUND: Over the past two decades, several studies have been conducted that have tried to answer questions on management of patients with acute heart failure (AHF) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) have endorsed the findings of these studies. The aim of this document was to adapt recommendations of existing guidelines to help internists make decisions about specific and complex scenarios related to AHF. METHODS: The adaptation procedure was to identify firstly unresolved clinical problems in patients with AHF in accordance with the PICO (Population, Intervention, Comparison and Outcomes) process, then conduct a critical assessment of existing CPGs and choose recommendations that are most applicable to these specific scenarios. RESULTS: Seven PICOs were identified and CPGs were assessed. There is no single test that can help clinicians in discriminating patients with acute dyspnoea, congestion or hypoxaemia. Performing of echocardiography and natriuretic peptide evaluation is recommended, and chest X-ray and lung ultrasound may be considered. Treatment strategies to manage arterial hypotension and low cardiac output include short-term continuous intravenous inotropic support, vasopressors, renal replacement therapy, and temporary mechanical circulatory support. The most updated recommendations on how to treat specific patients with AHF and certain comorbidities and for reducing post-discharge rehospitalization and mortality are provided. Overall, 51 recommendations were endorsed and the rationale for the selection is provided in the main text. CONCLUSION: Through the use of appropriate tailoring process methodology, this document provides a simple and updated guide for internists dealing with AHF patients.

Beyond clinical trials - The cost saving associated with dapagliflozin use in Portugal hospital clinical practice.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals. METHODS: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials. RESULTS: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1612851.54 up to EUR 6587360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data. CONCLUSIONS: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals.

Systolic and diastolic dysfunction in cirrhosis: a tissue-Doppler and speckle tracking echocardiography study.

BACKGROUND & AIMS: Cardiac dysfunction has been described in patients with cirrhosis. Conventional echocardiographic methods are frequently unable to detect abnormalities at rest and have limitations. We aimed to evaluate cardiac function in cirrhosis patients assessing: (i) left ventricular systolic function using speckle-tracking imaging; (ii) diastolic function using a tissue-Doppler based algorithm and comparing it with previously proposed definition of diastolic dysfunction (DD). METHODS: We included 109 hospitalized and ambulatory patients with cirrhosis and 18 healthy controls. Detailed echocardiographic evaluation was performed including tissue-Doppler and speckle-tracking analysis. RESULTS: Peak systolic longitudinal strain (PLS) was lower in patients [-19.99% (-21.88 to -18.71) vs -22.02% (-23.10 to -21.18), P = 0.003]. Ejection fraction was similar in patients and controls [64% (59-67) vs 61% (60-65), P = 0.42)]. Based on mitral-flow pattern, DD was present in 44 patients (40.4%). Patients without DD had higher cardiac output compared with those with DD [6.4 L/min (5.4-7.2) vs 5.6 L/min (4.6-6.8), P = 0.02]. Using a tissue-Doppler based definition, the prevalence of DD was 16.5%. No differences in haemodynamic variables were found in patients with and without this definition of DD. The agreement between the two definitions of DD was weak (kappa = 0.24, P = 0.003). Echocardiographic abnormalities in systolic and diastolic function were not different in compensated vs decompensated patients in different Child-Pugh classes or cirrhosis aetiologies. CONCLUSIONS: Patients with cirrhosis have systolic and diastolic cardiac dysfunction at rest. Newer echocardiographic techniques may identify patients with functional impairment more accurately than conventional methods, which are more influenced by flow conditions.

Mean platelet volume is associated with the presence of left atrial stasis in patients with non-valvular atrial fibrillation.

BACKGROUND: Mean platelet volume has been associated with stroke in patients with atrial fibrillation. However, its role as a predictor of left atrial stasis, assessed by transesophageal echocardiography, in patients with non-valvular atrial fibrillation has not yet been clarified. METHODS: Single center cross-sectional study comprising 427 patients admitted to the emergency department due to symptomatic atrial fibrillation and undergoing transesophageal echocardiogram evaluation for exclusion of left atrial appendage thrombus before cardioversion. All patients had a complete blood count performed in the 12 hours prior to transesophageal echocardiogram. Markers of left atrial stasis were sought: left atrial appendage thrombus, dense spontaneous echocardiographic contrast and low flow velocities in the left atrial appendage. The presence of at least one of the former markers of left atrial stasis was designated left atrial abnormality. Binary logistic multivariate analysis was used for obtaining models for the prediction of transesophageal echocardiogram endpoints. RESULTS: Left atrial appendage thrombus was found in 12.2%, dense spontaneous echocardiographic contrast in 29.7%, low flow velocities in 15.3% and left atrial abnormality in 34.2%. Mean platelet volume (exp ß = 3.41 p = 0.048) alongside with previous stroke or transient ischemic attack (exp ß = 5.35 p = 0.005) and troponin I (exp ß = 5.07 p = 0.041) were independent predictors of left atrial appendage thrombus. Mean platelet volume was also incorporated in the predictive models of dense spontaneous echocardiographic contrast, low flow velocities and left atrial abnormality, adding predictive value to clinical, echocardiographic and laboratory variables. CONCLUSIONS: These findings suggest that mean platelet volume may be associated with the presence of markers of left atrial stasis, reinforcing a likely cardioembolic mechanism for its association with stroke in patients with non-valvular atrial fibrillation.

Nutritional Risk and Malnutrition in Paediatrics: From Anthropometric Assessment to Strongkids® Screening Tool.

INTRODUCTION: The prevalence of malnutrition in hospitalized children is high and is associated with negative health impact. The aim of this study was to characterize the nutritional status of hospitalized children as well as comparing nutritional risk stratification using the STRONGkids® tool and anthropometric assessment. MATERIAL AND METHODS: A prospective study was conducted between March and June 2019 in a paediatric unit of a district hospital. Children with ages between one month and 17 years were included. Nutritional screening (STRONGkids®) was performed, and demographic and anthropometric variables were assessed by trained doctors and nurses (z-scores for height-for-age, weight-for-age, weight-for-height and body mass index were compared to the World Health Organization reference values) and related to the underlying condition (cause of hospitalization; hospital stay; the presence of chronic disease). RESULTS: A total of 209 children were evaluated, 188 of whom were included. Median age was 4.6 years and median hospital length of stay was four days. Fifty-four per cent were classified with "moderate risk" and 2% with "high risk" of developing malnutrition; 25% were effectively malnourished. Of the 105 children for which it was possible to calculate the z-scores, 6% presented acute malnutrition and nearly 14% presented chronic malnutrition. The STRONGkids® score correlated positively with nutritional status on admission, disease type on admission, and presence of previous underlying disease (p < 0.05). CONCLUSION: STRONGkids® is a simple, quick nutritional screening tool for hospitalized children that is related to nutritional status on admission. Given that a considerably high percentage of children were identified as being at risk for malnutrition, it is essential to identify this early and provide nutritional intervention during hospitalization.

Treating Advanced Hepatocellular Carcinoma with Sorafenib: A 10-Year Single Center Experience.

Introduction: Sorafenib was the first therapy used for systemic treatment of unresectable hepatocellular carcinoma (HCC). Multiple prognosis factors associated with sorafenib therapy have been described. Objectives: The aim of this work was to evaluate survival and time to progression (TTP) on HCC patients treated with sorafenib, and check for predictive factors of sorafenib benefit. Materials and Methods: Retrospectively, data from all HCC patients treated with sorafenib in a Liver Unit from 2008 to 2018 were collected and analyzed. Results: Sixty-eight patients were included; 80.9% were male, the median age was 64.5 years, 57.4% had Child-Pugh A cirrhosis and 77.9% were BCLC stage C. Macrovascular invasion (MVI) was present in 25% of the patients and 25% of the subjects had other extrahepatic metastasis. The median survival was 10 months (IQR 6.0-14.8) and median TTP was 5 months (IQR 2.0-7.0). Survival and TTP were similar between Child-Pugh A and B patients: 11.0 months (IQR 6.0-18.0) for Child-Pugh A and 9.0 months (IQR 5.0-14.0) for Child-Pugh B (p = 0.336). In univariate analysis, larger lesion size (LS >5 cm), higher alpha-fetoprotein (AFP >50 ng/mL), and no history of locoregional therapy were statistically associated with mortality (HR 2.17, 95% CI 1.24-3.81; HR 3.49, 95% CI 1.90-6.42; HR 0.54, 95% CI 0.32-0.93, respectively), but only LS and AFP were independent predictive factors, as shown in multivariate analysis (LS: HR 2.08, 95% CI 1.10-3.96; AFP: HR 3.13, 95% CI 1.59-6.16). MVI and LS >5 cm were associated with TTP shorter than 5 months in univariate analysis (MVI: HR 2.80, 95% CI 1.47-5.35; LS: HR 2.1, 95% CI 1.08-4.11), but only MVI was an independent predictive factor of TTP shorter than 5 months (HR 3.42, 95% CI 1.72-6.81). Regarding safety data, 76.5% of patients reported at least one side effect (any grade), and 19.1% presented grade III-IV adverse effects leading to treatment discontinuation. Conclusions: We observed no significant difference in survival or TTP in Child-Pugh A or Child-Pugh B patients treated with sorafenib, as compared to more recent real-life studies. Lower primary LS and AFP were associated with a better outcome, and lower AFP was the main predictor of survival. The reality of systemic treatment for advanced HCC has recently changed and continues to evolve, but sorafenib remains a viable therapeutic option.

Introdução: O sorafenib foi o primeiro fármaco usado em primeira linha na terapêutica sistémica do carcinoma hepatocelular (CHC) em estadio avançado. Têm sido descritos múltiplos factores modificadores de prognóstico associados à sua utilização. Objectivos: Caracterizar um grupo de doentes com CHC que realizaram terapêutica com sorafenib, estudar a sobrevivência e o tempo até progressão (TAP), e avaliar os factores preditores de benefício. Material e Métodos: Estudo retrospectivo com recolha e análise dos dados relativos a todos os doentes com CHC tratados com sorafenib numa Unidade de Hepatologia, entre 2008 e 2018. Resultados: Foram incluídos no estudo sessenta e oito doentes; 80.9% do sexo masculino, com mediana de idades de 64.5 anos, 57.4% tinham cirrose em estadio A de Child-Pugh e 77.9% apresentavam CHC em estadio C do Barcelona Clínic Liver Cancer (BCLC). A invasão macrovascular (IMV) estava presente em 25% dos doentes, e também 25% dos doentes tinha metastização extra-hepática (que não a IMV). A mediana de sobrevivência foi de 10 meses (IQR 6.0-14.8) e a mediana de TAP foi de 5 meses (IQR 2.0­7.0). A sobrevivência e o TAP foram similares nos doentes Child-Pugh A e B: 11.0 meses (IQR 6.0­18.0) para Child-Pugh A e 9.0 meses (IQR 5.0­14.0) para Child-Pugh B (p = 0.336). Na análise univariada, o tamanho da lesão >5 cm (TL), alfa-fetoproteína > 50 ng/mL (AFP) e a ausência de terapêuticas locorregionais prévias (TLP) tiveram relação estatisticamente significativa com a mortalidade (TL: HR 2.17, 95% CI 1.24­3.81; AFP: HR 3.49, 95% CI 1.90­6.42; TLP: HR 0.54, 95% CI 0.32­0.93), mas apenas o TL e AFP foram fatores preditores independentes, como mostrou a análise multivariada (TL: HR 2.08, 95% CI 1.10­3.96; AFP: HR 3.13, 95% CI 1.59­6.16). A IMV e o TL >5 cm estiveram associados com o TAP <5 meses na análise univariada (IMV: HR 2.80, 95% CI 1.47­5.35; TL: HR 2.1, 95% CI 1.08­4.11), mas apenas a IMV foi um fator preditor independente de TAP <5 meses (HR 3.42, 95% CI 1.72­6.81). Relativamente aos dados de segurança, 76.5% dos doentes relataram pelo menos um efeito lateral (qualquer grau), e 19.1% apresentaram efeitos adversos de grau III-IV, que levaram à suspensão do fármaco. Conclusões: Não foi observada diferença significativa na sobrevivência ou no tempo até progressão nos doentes Child-Pugh A ou Child-Pugh B tratados com sorafenib, quando comparado com estudos real-life recentes. Menor TL e AFP estiveram associados a melhor outcome e um valor de AFP baixo mostrou-se o principal preditor de sobrevivência. A realidade da terapêutica sistémica para o CHC avançado alterou-se recentemente e continua em mudança, mas o sorafenib permanece uma alternativa terapêutica viável.

Priapism Secondary to Low-Molecular-Weight Heparins: A Case Report.

Priapism may be a side effect of low-molecular-weight heparins, and its mechanism remains unknown. The authors present a clinical case of a 51-year-old male patient with oligodendroglioma. The patient presented ischemic priapism on the third month after starting tinzaparin, without other recent changes to his medication and he denied the use of other new medicines. The patient went through surgery and the erection was resolved but presented fibrosis of the cavernous body which left him with erectile dysfunction. Since this event, the patient is no longer receiving Heparin and has had no other episodes of priapism. The prompt recognition of this side effect may decrease its morbidity and consequent impact on the quality of life. More studies are needed to better understand its pathophysiology.

O priapismo pode ser um efeito adverso das heparinas de baixo peso molecular, cuja fisiopatologia não é totalmente compreendida. Os autores apresentam o caso de um doente, do sexo masculino, 51 anos, com diagnóstico de oligodendroglioma. O doente apresentou um episódio de priapismo, no terceiro mês sob tinzaparina, sem nenhuma outra alteração recente da sua medicação habitual e com consumo de outros medicamentos negado. Foi submetido a cirurgia, com resolução do priapismo, mas apresentou fibrose sequelar dos corpos cavernosos, com consequente disfunção eréctil. Desde então o doente não retomou heparina e não apresentou novos episódios de priapismo. Um célere reconhecimento do quadro pode contribuir para menores sequelas, com consequente diminuição da morbilidade e impacto na qualidade de vida. Mais investigação é necessária para aumentar o conhecimento sobre a fisiopatologia desta situação.

The Association between Childhood Obesity and Cardiovascular Changes in 10 Years Using Special Data Science Analysis.

The increasing prevalence of overweight and obesity is a worldwide problem, with several well-known consequences that might start to develop early in life during childhood. The present research based on data from children that have been followed since birth in a previously established cohort study (Generation XXI, Porto, Portugal), taking advantage of State-of-the-Art (SoA) data science techniques and methods, including Neural Architecture Search (NAS), explainable Artificial Intelligence (XAI), and Deep Learning (DL), aimed to explore the hidden value of data, namely on electrocardiogram (ECG) records performed during follow-up visits. The combination of these techniques allowed us to clarify subtle cardiovascular changes already present at 10 years of age, which are evident from ECG analysis and probably induced by the presence of obesity. The proposed novel combination of new methodologies and techniques is discussed, as well as their applicability in other health domains.

conTemporary reflectiOns regarding heart failure manaGEmenT - How to ovERcome the PorTuguese barriers (TOGETHER-PT).

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a complex clinical syndrome that is a significant burden in hospitalisations, morbidity, and mortality. Although a significant effort has been made to better understand its consequences and current barriers in its management, there are still several gaps to address. The present work aimed to identify the views of a multidisciplinary group of health care professionals on HF awareness and literacy, diagnosis, treatment and organization of care, identifying current challenges and providing insights into the future. METHODS: A steering committee was established, including members of the Heart Failure Study Group of the Portuguese Society of Cardiology (GEIC-SPC), the Heart Failure Study Group of the Portuguese Society of Internal Medicine (NEIC-SPMI) and the Cardiovascular Study Group (GEsDCard) of the Portuguese Association of General and Family Medicine (APMGF). This steering committee produced a 16-statement questionnaire regarding different HF domains that was answered to by a diversified group of 152 cardiologists, internists, general practitioners, and nurses with an interest or dedicated to HF using a five-level Likert scale. Full agreement was defined as ≥80% of level 5 (fully agree) responses. RESULTS: Globally, consensus was achieved in all but one of the 16 statements. Full agreement was registered in seven statements, namely 3 of 4 statements for patient education and HF awareness and 2 in 4 statements of both HF diagnosis and healthcare organization, with proportions of fully agree responses ranging from 82.9% to 96.7%. None of the HF treatment statements registered full agreement but 3 of 4 achieved ≥80% of level 4 (agree) responses. CONCLUSION: This document aims to be a call-to-action to improve HF patients' quality of life and prognosis, by promoting a change in HF care in Portugal.

Thrombosis and cachexia in cancer: Two partners in crime?

Among cancer patients, thrombosis and cachexia are major causes of morbidity and mortality. Although the two may occur together, little is known about their possible relationship. Thus, a literature review was conducted by screening the databases PubMed, Scopus, SciELO, Medline and Web of Science. To summarize, cancer-associated thrombosis (CAT) and cancer-associated cachexia (CAC) seem to share several patient-, tumour- and treatment-related risk factors. Inflammation alongside metabolic and endocrine derangement is the potential missing link between CAT, CAC and cancer. Many key players, including specific pro-inflammatory cytokines, immune cells and hormones, appear to be implicated in both thrombosis and cachexia, representing attractive predictive markers and potential therapeutic targets. Altogether, the current evidence suggests a link between CAT and CAC, however, epidemiological studies are required to explore this potential relationship. Given the high incidence and negative impact of both diseases, further studies are needed for the better management of cancer patients.

Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer.

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Khorana score (KS) is the most studied tool to predict cancer-related VTE, however, it exerts poor sensitivity. Several single-nucleotide polymorphisms (SNPs) have been associated with VTE risk in the general population, but whether they are predictors of cancer-related VTE is a matter of discussion. Compared to other solid tumours, little is known about VTE in the setting of cervical cancer (CC) and whether thrombogenesis-related polymorphisms could be valuable biomarkers in patients with this neoplasia. This study aims to analyse the effect of VTE occurrence on the prognosis of CC patients, explore the predictive capability of KS and the impact of thrombogenesis-related polymorphisms on CC-related VTE incidence and patients' prognosis regardless of VTE. A profile of eight SNPs was evaluated. A retrospective hospital-based cohort study was conducted with 400 CC patients under chemoradiotherapy. SNP genotyping was carried on by using TaqMan® Allelic Discrimination methodology. Time to VTE occurrence and overall survival were the two measures of clinical outcome evaluated. The results indicated that VTE occurrence (8.5%) had a significant impact on the patient's survival (log-rank test, P < 0.001). KS showed poor performance (KS ≥ 3, χ2, P = 0.191). PROCR rs10747514 and RGS7 rs2502448 were significantly associated with the risk of CC-related VTE development (P = 0.021 and P = 0.006, respectively) and represented valuable prognostic biomarkers regardless of VTE (P = 0.004 and P = 0.010, respectively). Thus, thrombogenesis-related genetic polymorphisms may constitute valuable biomarkers among CC patients allowing a more personalized clinical intervention.