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.

Beyond Clinical Trials - The cost-saving associated with dapagliflozin use in portuguese 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 1 612 851.54 up to EUR 6 587 360.09, 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.

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.

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.

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.

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.

Unilateral testicular torsion in a neonate / Torsão testicular unilateral em neonato

A male neonate born at gestational age of 40 weeks was found to have an enlarged and darkened right hemiscrotum after birth. Left testicle was descended and normal. No clinical signs of distress were evident. A color Doppler ultrasound showed an absence of testicular blood flow, consistent with perinatal testicular torsion. The patient underwent a bilateral scrotal exploration through an inguinal incision and a necrotic right testicle was found. A right orchiectomy and left orchiopexy were performed. Perinatal testicular torsion is a rare but severe condition. A high clinical suspicion is required since most of perinatal testicular torsion are intrauterine and can often be asymptomatic, only with localized findings of the affected testis. The management of perinatal testicular torsion is still controversial; however, the most consensual approach is a prompt testicle exploration with orchiectomy of the necrotic testicle and contralateral orchiopexy

Recém-nascido do sexo masculino com idade gestacional de 40 semanas, com edema e escurecimento cutâneo do hemiescroto direito constatados após o nascimento. O testículo esquerdo era palpável na bolsa escrotal e não apresentava alterações. A ecografia escrotal com Doppler revelou ausência de fluxo vascular no testículo direito, achado compatível com torção testicular perinatal. O doente foi submetido a exploração escrotal bilateral através de abordagem por via inguinal, tendo sido confirmada a necrose do testículo direito. Foi realizada orquidectomia direita e orquidopexia esquerda. A torção testicular perinatal corresponde a uma patologia rara, mas com possíveis consequências graves. O seu diagnóstico requer elevada suspeição clínica, uma vez que a maioria dos casos ocorre no período pré-natal, podendo ser assintomáticos após o nascimento e manifestar-se com alterações localizadas ao testículo afetado. A abordagem da torção testicular perinatal é ainda controversa, sendo mais consensual uma exploração escrotal célere com orquidectomia do testículo necrosado e orquidopexia contralateral

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.

Espondilodiscite em idade pediátrica ­ uma doença rara, um diagnóstico difícil / Spondylodiscitis in pediatric age ­ a rare disease, a difficult diagnosis

Introdução e objetivo: a espondilodiscite é a infeção que atinge o disco intervertebral e as vértebras contíguas e representa dois a quatro % do total das infeções osteoarticulares em idade pediátrica. O agente patogénico é identificado em cerca de metade dos casos, sendo o Staphylococcus aureus o mais frequentemente isolado. Estudos recentes demonstram que entre os seis meses e os quatro anos a Kingella kingae tem um papel etiológico importante. O objetivo da exposição deste caso clínico foi chamar atenção para esta patologia rara cujo diagnóstico é difícil e exige um elevado nível de suspeição. Descrição do caso: criança de 16 meses, sexo masculino, com antecedentes de obstipação, é trazida múltiplas vezes à Urgência Pediátrica por quadro com mais de um mês de evolução de irritabilidade persistente, dor abdominal e recusa da marcha de agravamento progressivo. Na segunda vinda à Urgência Pediátrica apresentava dorsolombalgia à palpação da coluna dorsolombar e diminuição da lordose lombar, o que motivou a realização de avaliação analítica, sumária de urina, ecografia renal e vesical e radiografia dorsolombar sem alterações. Na terceira vinda à Urgência Pediátrica foi decidido internamento e solicitada ressonância magnética nuclear dorsolombar e cintigrafia óssea que revelaram espondilodiscite em D7-D8. Parâmetros analíticos sem alterações valorizáveis, exceto discreta elevação da velocidade de sedimentação. Hemoculturas e restante estudo etiológico negativo. Iniciou terapêutica endovenosa com cefu-roxime e flucloxacilina, com melhoria progressiva das queixas álgicas. Aquando da alta, assintomático, mantendo flucloxacilina oral até completar seis semanas de tratamento. Reavaliado posteriormente, encontrando-se assintomático, com um exame físico, reavaliação analítica e radiografia dorsolombar sem alterações. Conclusões: a espondilodiscite é uma identidade de difícil diagnóstico, especialmente na criança, devido à sua raridade, clínica inespecífica, impossibilidade de as crianças verbalizarem os seus sintomas e aos sinais radiológicos tardios, requerendo um alto índice de suspeição. O intervalo médio de tempo entre o início dos sintomas e o diagnóstico é de três semanas a três meses. A ressonância magnética é o exame de escolha. As hemoculturas são, muitas vezes, negativas. O pilar do tratamento é a antibioterapia por várias semanas, mas a sua escolha e duração são controversas. O tratamento inadequado pode originar dor crônica, sequelas ortopédicas graves e complicações neurológicas devastadoras. Quando atempada e adequadamente tratada, a maioria dos casos apresenta uma evolução clínica benigna e autolimitada.

Introduction and objective: spondylodiscitis is an infection that affects the intervertebral disc and the contiguous vertebrae. It represents two to four % of all osteoarticular infections in pediatric age. The pathogen is identified in about half of the cases, with Staphylococcus aureus being the most frequently isolated. Recent studies show that between six months and four years, Kingella kingaehas an important etiological role. The purpose of the presentation of this clinical case was to draw attention to this rare pathology whose diagnosis is difficult and requires a high level of suspicion. Clinical case description: a sixteen-month-old male, with a history of constipation, is brought multiple times to the Pediatric Emergency Department for a clinical picture with more than a month of evolution of persistent irritability, abdominal pain and refusal to walk, with progressive worsening. On the second visit to the Pediatric Emergency Department, he presented dorsolombalgia on palpation of the dorsolumbar spine and decreased lumbar lordosis, which led to the performance of analytical evaluation, urinalysis, renal and bladder ultrasound and dorsolumbar radiography, all without changes. On the third visit to the Pediatric Emergency Department, hospitalization was decided and dorsolumbar nuclear magnetic resonance and bone scintigraphy were requested, revealing spondylodiscitis in D7-D8. Analytical parameters had no changes, except for a slight increase in erythrocyte sedimentation rate. Blood cultures and remaining etiological study negatives. Intravenous therapy with cefuroxime and flucloxacillin was started with progressive improvement of pain. Upon discharge he was asymptomatic and maintained oral flucloxacillin until a total of six weeks of treatment. He was subsequently reassessed and remained asymptomatic, with a physical examination, analytical evaluation and dorsolumbar radiography without changes. Conclusions: spondylodiscitis is an identity that is difficult to diagnose, especially in children, due to its rarity, unspecific clinic, inability for children to verbalize their symptoms and late radiologic signs, requiring a high index of suspicion. The average time between the onset of symptoms and the diagnosis is three weeks to three months. Magnetic resonance imaging is the exam of choice. Blood cultures are often negative. The mainstay of treatment is antibiotic therapy for several weeks, but its choice and duration are controversial. Inappropriate treatment can lead to chronic pain, severe orthopaedic sequelae and devastating neurological complications. When timely and properly treated, most cases have a benign and self-limited clinical course.