Venous thromboembolism-related genetic determinant F11 rs4253417 is a potential prognostic factor in ischaemic stroke.

Ischaemic stroke (IS) and venous thromboembolism (VTE) are two forms of thromboembolism that, although distinct, seem to share numerous risk factors. Concerning genetic risk factors, while many VTE genetic markers have been reported, inclusively by genome-wide association studies (GWAS), the identification and validation of genetic determinants underlying IS pathogenesis have been challenging. Considering that IS and VTE shared biological pathways and aetiological factors, the severity of IS might be also influenced by VTE-related genetic variants. Thus, the present study was designed to analyse the impact of six VTE GWAS-identified genetic variants on the clinical outcome of 363 acute IS patients. Results revealed that the single-nucleotide polymorphism (SNP) F11 rs4253417 was an independent predictor of the 5-year risk of death among patients with total anterior circulation infarct (TACI). Namely, the ones carrying the SNP C allele presented a fourfold increase in the 5-year risk of death compared to TT genotype carriers (CC/CT vs. TT; adjusted HR, 4.240; 95% CI, 1.260-14.270; P = 0.020). This SNP is known to be associated with coagulation factor XI (FXI) levels, thus with implications in haemostasis and inflammation. As such, F11 rs4253417 might be a promising prognostic biomarker among TACI patients to aid in clinical decision-making. However, additional investigation is required to confirm the study's results and dissect the underlying mechanisms.

Acquired Hemophilia A associated with bullous pemphigoid: A rare combination.

Acquired Hemophilia A (AHA) is a rare autoimmune disorder, caused by the development of circulating autoantibodies against coagulation factor VIII (FVIII). AHA is associated with bullous pemphigoid in 2% of patients. We report a case of a 74-year-old man admitted with anemia and a tense subcutaneous and muscular hematoma in the right thigh. Blood analysis confirmed AHA. The patient had a recent diagnosis of bullous pemphigoid. Response to bypass agents and corticosteroids was good with bleeding control and normalization of FVIII and negative autoantibodies, respectively. In a 3-month follow-up period after tapering and stopping prednisolone, a relapse occurred, and immunosuppression was reinitiated. An early diagnosis and effective treatment in AHA are essential to reduce morbimortality. A careful tapering of immunosuppression is important to minimize FVIII inhibitor recurrence, as observed in this case.

Can the previous therapeutic control of the main risk factors of cerebrovascular disease influence the acetylsalicylic Acid-nonresponsive status in acute ischemic stroke patients? Results from a portuguese prospective cohort study.

BACKGROUND: Acute ischemic stroke (AIS) is a complex disease, and the therapeutic control of its risk factors may influence the efficacy of acetylsalicylic acid (ASA) and the occurrence of new vascular events. The aim of this study was to investigate the potential in vivo properties of a previous treatment controlling the main risk factors of cerebrovascular disease, in the ASA-nonresponsive status in a Portuguese population. METHODS: We conducted a prospective cohort study with the recruitment of 90 patients diagnosed with AIS and a follow-up protocol was set up with recurrent stroke as the main clinical end point under evaluation. At admission, PFA-100 (platelet function analyzer) test was evaluated in blood samples from AIS patients treated with 100 mg/day of ASA and previously treated with antihypertensive, antidiabetic, or statin drugs. RESULTS: We observed that 30% of patients were ASA nonresponders. Multivariate regression analysis indicated that the previous treatment with antihypertensive drugs emerged with a significant risk reduction of an ASA-nonresponsive status (odds ratio, .119; 95% confidence interval, .026-.538; P = .006). Furthermore, our results indicated an influence of ASA-nonresponsive status in a decreased period to a new recurrent stroke event in the time frame of 24 months (P = .005, log-rank test). CONCLUSIONS: ASA is an important part of treatment of AIS, and its efficacy may be improved in previous high-risk cerebrovascular patients, particularly with antihypertensive therapeutic control.

The platelet-to-lymphocyte ratio as an indirect outcome predictor in primary hypertension: a retrospective study.

Background: Nondipper hypertensive patients have higher levels of platelet-to-lymphocyte ratio, a new studied inflammatory biomarker in primary hypertension. Furthermore, these patients have a higher risk of cardiovascular morbidity and mortality. This study aimed to assess the relationship between platelet-to-lymphocyte ratio and hypertensive pattern (dipper vs nondipper) and the association between the hypertensive pattern and major adverse cardiovascular events. Methods: A retrospective analysis was performed. One hundred fifty-three patients were included and classified as dipper or nondipper according to 24-hour ambulatory blood pressure measurements. Platelet-to-lymphocyte ratio was calculated based on complete blood count data. Results: The dipper group included 109 patients, and the nondipper group included 44 patients. Nondipper patients have 2.11 more risk of presenting a higher platelet-to-lymphocyte ratio than dipper individuals (odds ratio [OR] = 2.11; 95% CI, 1.220-3.664; P = .007). Nondipper patients also registered earlier cardiovascular events, such as acute myocardial infarction and stroke (P < .001). Conclusions: Nondipper hypertensive individuals registered higher levels of platelet-to-lymphocyte ratio and earlier cardiovascular events than dipper patients. Therefore, platelet-to-lymphocyte ratio could be used as an indirect predictor of cardiovascular risk in primary hypertension and contribute to optimize preventive strategies.

Risk factors among stroke subtypes and its impact on the clinical outcome of patients of Northern Portugal under previous aspirin therapy.

BACKGROUND: In Western European countries, acute ischemic stroke (AIS) remains the third leading cause of death. Among the risk factors for cerebrovascular disease, some have more influence than others in certain stroke subtypes. The aim of this study was to evaluate the impact of risk factors among Stroke Subtypes on the clinical outcome of Portuguese patients under previous aspirin therapy. MATERIALS AND METHODS: We studied a cohort of 371 patients diagnosed with AIS and a clinical follow-up protocol was set up.The patients were admitted in a Department of Internal Medicine of a major hospital. Standardized data assessment and stroke subtype classification (Oxfordshire Community Stroke Project) were used. RESULTS: Arterial hypertension (80.4 %), overweight (72.6 %) and dyslipidemia (62.0 %) were the most prevalent risk factors with no statistical differences among the group's subtypes. Current smoking was more prevalent in POCI(62.9 %) with differences among subtypes (p = 0.002). Atrial fibrillation was more commonly reported in TACI (39.3 %) and less common in POCI (8.1 %) (p < 0.001).Comparing TACI vs Non TACI Stroke Subtypes demonstrated major differences in cumulative survival,among the cases with no previous aspirin treatment, after 3 years (51.9 % vs 88.8 %).The increased risk of mortality at 12 months is consistently observed for the presence of a previous atrial fibrillation (OR 3.01 95 %CI 1.69-5.39), TACI subtype (OR 10.4 95 %CI 4.83-22.6) and NIHSS over 10 (OR 9.33 95 % CI 4,49-19.4). When we analyze the impact of previous aspirin treatment in the risk for a new stroke event, it seems to have a protective effect in a time frame of 12 months, but this protection is lost extending at 24 months (p = 0.094 vs p = 0.005). DISCUSSION: Our results indicate that smoking, atrial fibrillation and age have different relevance in their distribution among ischemic stroke subtypes at the time of diagnosis. Concerning the influence of the main stroke risk factors on the clinical outcome, our results present a strong influence of atrial fibrillation and of age. Severity of disease at diagnosis, represented by TACI subtype is clearly associated to decreased survival among patients with no record of previous aspirin therapy. Our results reinforce the relevance cohort studies of different populations, to achieve a more comprehensive knowledge of the impact of risk factors on stroke subtypes and on its clinical outcome.

Pancoast Tumor as the Initial Presentation of a Metastatic Colon Adenocarcinoma.

A Pancoast tumor is a rare condition, representing 3% to 5% of all lung cancers. The particular location of these lesions leads to the invasion of structures in the thoracic inlet, causing a constellation of symptoms known as Pancoast-Tobias syndrome. Diagnosis can be challenging due to their low prevalence and the possibility of being asymptomatic. Most of these tumors are non-small cell lung cancers. However, rare conditions might arise at the same location, and histologic confirmation is relevant. We report the case of a 45-year-old man admitted to the internal medicine department with a one-month history of night sweats. A full-body computed tomography (CT) scan revealed a mass on the upper lobe of the left lung, with soft tissue invasion. Histopathologic examination revealed an adenocarcinoma pattern originating from the colon. Colonoscopy showed two synchronous lesions. Hitherto, this is the second case ever described of a Pancoast tumor as metastasis of colon adenocarcinoma.

Low density lipoprotein cholesterol values and outcome of stroke patients: influence of previous aspirin therapy.

Background: The link between low-density lipoprotein cholesterol (LDL-C) and stroke risk remains controversial and few studies have evaluated the effect of LDL-C after stroke survival.Aims: We assessed the hypothesis proposing the effect of LDL-C on the outcome of stroke patients under the influence of previous Aspirin Therapy.Methods: Associations between LDL-C and outcomes. The effect of LDL cholesterol on stoke outcome was evaluated using Kaplan-Meier methodology, log-rank test, Cox proportional hazard models and Bootstrap Analysis.Results: In a cohort of 342 cases, we observed that among stroke patients with no record of previous aspirin therapy LDL-C levels within recommended range (nLDL-C) are associated to a poor overall survival on (p < 0.001, log-rank test) leading to a 4-fold increased mortality risk in both timeframes of 12 (HR 4.45, 95% CI 1.55-12.71; p = 0.004) or 24 months (HR 4.13, 95%CI 1.62-10.50;p = 0.003) after the first event of stroke. Moreover, modelling the risk of a second event after the first stroke in the timeframe of 24 months demonstrated a predictive capacity for nLDL-C plasmatic levels (HR 3.94, 95%CI 1.55-10.05; p = 0.004) confirmed by Bootstrap analysis (p = 0.003; 1000 replications). In a further step, the inclusion of LDL-C in simulating models equations to predict the risk of a second event in the timeframe of 12 months increased nearly 20% the predictive ability (c-index from 0.763 to 0.956).Conclusion: A worse outcome was seen in stroke patients with normal levels of LDLC, but this finding was restricted to patients not under previous aspirin therapy.

The emergent phenomenon of aspirin resistance: insights from genetic association studies.

Despite the clinical benefits of aspirin, the interindividual variation in response to this antiplatelet drug is considerable. The manifestation of aspirin resistance (AR) is frequently observed, although this complex process remains poorly understood. While AR etiology is likely to be multifactorial, genetic factors appear to be preponderant. According to several genetic association studies, both genome-wide and candidate gene studies, numerous SNPs in cyclooxygenase, thromboxane and platelet receptors-related genes have been identified as capable of negatively affecting aspirin action. Thus, it is essential to understand the clinical relevance of AR-related SNPs as potential predictive and prognostic biomarkers as they may be essential to defining the AR phenotype.

GWAS contribution to atrial fibrillation and atrial fibrillation-related stroke: pathophysiological implications.

Atrial fibrillation (AF) and stroke are included in a group of complex traits that have been approached regarding of their study by susceptibility genetic determinants. Since 2007, several genome-wide association studies (GWAS) aiming to identify genetic variants modulating AF risk have been conducted. Thus, 11 GWAS have identified 26 SNPs (p < 5 × 10-2), of which 19 reached genome-wide significance (p < 5 × 10-8). From those variants, seven were also associated with cardioembolic stroke and three reached genome-wide significance in stroke GWAS. These associations may shed a light on putative shared etiologic mechanisms between AF and cardioembolic stroke. Additionally, some of these identified variants have been incorporated in genetic risk scores in order to elucidate new approaches of stroke prediction, prevention and treatment.

The Importance of Computed Tomography Findings in Detecting Tuberculous Addison's Disease.

Addison's disease is an endocrine disorder characterized by primary adrenal insufficiency due to various causes. Mycobacterium tuberculosis infection was a major cause in the past but is rare nowadays. We describe a patient admitted to our hospital who was diagnosed with tuberculous Addison's disease. LEARNING POINTS: Tuberculosis is a rare cause of Addison's disease in developed countries and so diagnosis is a clinical challenge and requires a high index of suspicion.Tuberculosis should always be considered as a cause of Addison's disease since treating active tuberculosis with steroids alone may have serious consequences.Computed tomography findings can be very helpful in the diagnosis of tuberculous Addison's disease.

Angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women.

Endometrial carcinoma is one of the most common gynecological malignancies. Most cases are diagnosed in older patients with diabetes, hypertension, or obesity. The renin-angiotensin system (RAS) has a central role controlling blood pressure and sodium homeostasis. RAS polymorphisms have been reported as genetic determinants of essential hypertension. The objective of this study was to analyze angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. The presence of an angiotensin converting enzyme (ACE) polymorphism was analyzed by polymerase chain reaction in DNA isolated from peripheral blood samples of 171 women: 70 cases with endometrial cancer (age, 63.6 +/- 9.5 years) and 101 normal control women (age, 61.3 +/- 6.4 years). We detected DD genotype in 47.5%, ID genotype in 44.3%, and II genotype in 8.2% of cases. The allele frequency was 0.69 for D allele and 0.30 for I allele. In normotensives, we found that the presence of I allele (genotypes ID and II) is significantly associated to an earlier age (56.0 +/- 10.1 versus 65.8 +/- 9.9) of onset of endometrial carcinoma (P=0.029). We observed that normotensive women carriers of an allele I have a higher risk of development of endometrial cancer under the age of 63 years (odds ratio=3.60, 95% confidence interval=1.03-12.56; P=0.037). Our findings suggest that ACE polymorphism may be associated with the development of endometrial carcinoma and with the onset of this tumor in younger women. The definition of a pharmacogenomic profile of human neoplasia may help to identify targets for the development of therapeutic or chemoprevention strategies.

Acute renal failure as a form of presentation of sarcoidosis in a young adult: a case report.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease. Renal involvement is a rare initial presentation of this disease. Few articles on renal involvement as an initial presentation of sarcoidosis have been published in the literature. CASE PRESENTATION: A 26-year-old Caucasian woman presented with acute renal failure as an initial manifestation of sarcoidosis. CONCLUSIONS: Renal involvement is an uncommon feature of sarcoidosis and it is essential to establish a fast and correct diagnosis because early therapy avoids progression to terminal renal failure.

Renal failure due to primary amyloidosis: a case report and literature review.

CONTEXT: Primary amyloidosis, also known as AL amyloidosis, is commonly caused by clonal expansion of plasma cells in the bone marrow, thereby segregating light chains of clonal immunoglobulin that settle in tissues in the form of insoluble amyloid fibrils. The aim of this study was to report a case of primary amyloidosis with renal failure, diagnosed in Hospital São João, Porto, Portugal, focusing on the diagnostic difficulties and presenting a literature review. CASE REPORT: A 68-year-old Caucasian man was admitted to the Internal Medicine Department of the hospital with a condition of anasarca and nephrotic syndrome. After performing a renal biopsy that tested positive using Congo red and immunohistochemistry, lambda light chain amyloidosis was diagnosed. This evolved into terminal renal disease, which led to hemodialysis and several episodes of urinary and catheter infections. He was started on chemotherapy, consisting of bortezomib 0.7 mg/m(2) and dexamethasone 40 mg in six cycles. This led to clinical improvement, stabilization of the illness and good tolerance of the treatment. CONCLUSION: Amyloidosis is a rare entity that is difficult to diagnose. This is because of the unspecific early clinical manifestations of the disease. The hypothesis of amyloidosis is only considered when specific organ failure occurs. This case consisted of primary amyloidosis with involvement of the kidneys as an initial presentation of the disease and its difficulties were shown, going from the clinical approach to the final diagnosis.

Langerhans cell histiocytosis involving the liver of a male smoker: a case report.

INTRODUCTION: Langerhans' cell histiocytosis is a proliferative histiocytic disorder of unknown cause originating from dendritic cells. CASE PRESENTATION: The authors report a case of Langerhans' cell histiocytosis in a 48-year-old man with multisystemic disease presentation, including liver involvement. CONCLUSION: Hepatic involvement is an uncommon feature in this rare disease and there is no consensus on the most effective therapeutic approach.

Renal failure due to primary amyloidosis: a case report and literature review / Falência renal devida a amiloidose primária: um relato de caso e revisão da literatura

CONTEXT: Primary amyloidosis, also known as AL amyloidosis, is commonly caused by clonal expansion of plasma cells in the bone marrow, thereby segregating light chains of clonal immunoglobulin that settle in tissues in the form of insoluble amyloid fibrils. The aim of this study was to report a case of primary amyloidosis with renal failure, diagnosed in Hospital São João, Porto, Portugal, focusing on the diagnostic difficulties and presenting a literature review. CASE REPORT: A 68-year-old Caucasian man was admitted to the Internal Medicine Department of the hospital with a condition of anasarca and nephrotic syndrome. After performing a renal biopsy that tested positive using Congo red and immunohistochemistry, lambda light chain amyloidosis was diagnosed. This evolved into terminal renal disease, which led to hemodialysis and several episodes of urinary and catheter infections. He was started on chemotherapy, consisting of bortezomib 0.7 mg/m² and dexamethasone 40 mg in six cycles. This led to clinical improvement, stabilization of the illness and good tolerance of the treatment. CONCLUSION: Amyloidosis is a rare entity that is difficult to diagnose. This is because of the unspecific early clinical manifestations of the disease. The hypothesis of amyloidosis is only considered when specific organ failure occurs. This case consisted of primary amyloidosis with involvement of the kidneys as an initial presentation of the disease and its difficulties were shown, going from the clinical approach to the final diagnosis.

CONTEXTO: A amiloidose primária, também conhecida como amiloidose AL, é geralmente causada pela expansão clonal de plasmócitos na medula óssea que segregam cadeias leves de imunoglobulina clonal, as quais se depositam nos tecidos na forma de fibrilas amiloides insolúveis. O objetivo deste estudo é relatar um caso de amiloidose primária com acometimento renal diagnosticado no Hospital São João, Porto, Portugal, enfatizando as dificuldades do diagnóstico e apresentando uma revisão da literatura. RELATO DO CASO: Homem de 68 anos, branco, foi admitido no Serviço de Medicina Interna do hospital com quadro de anasarca e síndrome nefrótica. Após realizar biópsia renal, que foi positiva para o vermelho congo e imunoistoquímica, foi diagnosticada amiloidose de cadeia leve lambda. Evoluiu para doença renal terminal, o que levou a hemodiálise e tendo vários episódios de infecções urinárias e do cateter. Iniciou a quimioterapia com bortezimib, 0,7 mg/m², e dexametasona, 40 mg em seis ciclos, levando a uma melhoria clínica, a estabilização da doença e boa tolerância ao tratamento. CONCLUSÃO: Amiloidose consiste em uma entidade rara e de difícil diagnóstico. Isso ocorre devido a manifestações clínicas da doença pouco específicas, e esta hipótese só é considerada quando do acometimento de um órgão em particular. O caso em questão refere-se a uma apresentação da amiloidose primária com envolvimento renal, como apresentação clínica inicial da doença, e as dificuldades desde a abordagem clínica até o diagnóstico final.

Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome.

BACKGROUND: The glutathione S-transferases (GSTs) are a group of multifunctional enzymes that catalyze the conjugation of glutathione with a variety of electrophilic compounds, including cytotoxic agents. A significant percentage of normal individuals exhibit genetic polymorphism with a homozygous deletion (null genotype) of the genes, leading to absence of the enzyme. METHODS: In the present study we analyzed GSTM1 and GSTT1 polymorphisms in the genomic DNA isolated from peripheral blood of patients with ovarian cancer treated with chemotherapy (paclitaxel and cisplatinum) after cytoreductive surgery and assessed its correlation with the clinical outcome of these patients. The median follow-up for the patients was 30 months. RESULTS: The estimated 3-year survival rate was 59.8% for all patients and 20.8% for carriers of GSTM1-wt/GSTT1-wt (wt indicates wild type) genotype combination (37.7% for GSTM1-wt alone) compared with 83.1% for non-GSTM1-wt/GSTT1-wt genotype carriers (100% for GSTM1-null). The mean survival time was significantly better in patients who are carriers of the GSTM1-null genotype (40.5 vs. 33.5; P=0.006) or carriers of non-GSTM1-wt/ GSTT1-wt genotypes (55.4 vs. 30.7; P=0.009). The progression-free interval was more favorable for GSTM1-null carriers (41.9 vs. 27.4; P=0.024). CONCLUSION: The study suggests that characterization of the drug-metabolizing genetic individual profile can be of great interest in clinical oncology. It can define the optimal chemotherapy for each patient, improve the efficiency, and reduce the incidence of drug toxicity and poor drug responses.