Letizia Marconi

Is Incidentally Detected Pulmonary Embolism in Cancer Patients Less Severe? A Case-Control Study

Incidental pulmonary embolism (PE) in cancer patients is usually thought to be of mild degree. We investigated the severity of PE and evaluated the potential of raising the suspicion of PE in such patients. The computed tomography (CT) extent of PE was evaluated in 19 consecutive unsuspected and 19 randomly selected symptomatic patients. A clinical pattern useful for suspecting PE was also searched. On CT, number of embolized vessels, location of emboli, and simple instrumental findings were not different in the two groups. PE is not less severe in unsuspected cancer patients; moreover, PE may be clinically suspected in such patients.

Advantages of Real Time Three‐Dimensional Echocardiography in the Assessment of Right Ventricular Volumes and Function in Patients with Pulmonary Hypertension Compared with Conventional Two‐Dimensional Echocardiography

In recent years, right ventricular (RV) function has acquired greater relevance as a clinical and prognostic marker in many physiopathological conditions. The study aims to point out the value of real time three‐dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI) in the evaluation of patients affected by pulmonary hypertension (PH), compared with conventional two‐dimensional (2D) echocardiography.

Gly482Ser PGC-1α Gene Polymorphism and Exercise-Related Oxidative Stress in Amyotrophic Lateral Sclerosis Patients

The role of exercise in Amyotrophic lateral sclerosis (ALS) pathogenesis is controversial and unclear. Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that regulates mitochondrial biogenesis and antioxidant defense mechanisms. It has been suggested that a Gly482Ser substitution in PGC-1α has functional relevance in human disorders and in athletic performance. To test this hypothesis, we examined the genotype distribution of PGC-1α Gly482Ser (1444 G > A) in ALS patients to evaluate whether or not the minor serine-encoding allele 482Ser is involved in oxidative stress responses during physical exercise. We genotyped 197 sporadic ALS patients and 197 healthy controls in order to detect differences in allelic frequencies and genotype distribution between the two groups. A total of 74 ALS patients and 65 controls were then comparatively assessed for plasmatic levels of the oxidative stress biomarkers, advanced oxidation protein products, ferric reducing ability and thiol groups. In addition a subgroup of 35 ALS patients were also assessed for total SOD and catalase plasmatic activity. Finally in 28 ALS patients we evaluated the plasmatic curve of the oxidative stress biomarkers and lactate during an incremental exercise test. No significant differences were observed in the genotype distribution and allelic frequency in ALS patients compared to the controls. We found significant increased advanced oxidation protein products (p < 0.001) and significant decreased ferric reducing ability (p < 0.001) and thiol groups (p < 0.001) in ALS patients compared to controls. When comparing different genotypes of PGC-1α, no relation between Gly482Ser polymorphism and oxidative stress biomarker levels was detected in resting conditions. On the other hand, when considering exercise performance, lactate levels were significantly higher (between p < 0.01 and p < 0.001) and greater protein oxidative products were found in AA (Ser482Ser) compared to GG (Gly482Gly) and GA (Gly482Ser) ALS patients. Our findings highlight the importance and confirm the involvement of oxidative stress in ALS pathogenesis. Although not associated with 1444 G > A SNP, ALS patients with Gly482Ser allelic variant show increased exercise-related oxidative stress. This thus highlights the possible role of this antioxidant defense transcriptional coactivator in ALS.

The clinical course of pulmonary embolism patients anticoagulated for 1 year: results of a prospective, observational, cohort study.

Summary.  Background: Few studies have examined the clinical course of pulmonary embolism (PE) in patients anticoagulated continuously for 1 year. Objective: We sought to determine the incidence of death, recurrent PE and bleeding during anticoagulation in the first year after acute PE, and to assess associated risk factors. Methods: All consecutive PE patients who were referred to our center in Pisa, Italy between 2001 and 2005 received a conventional initial treatment, followed by vitamin K antagonists [international normalized ratio (INR), 2.0–3.0] for 1 year. They were followed‐up at scheduled times at the study center. The development of recurrent PE was objectively documented and recorded. Results: Out of 497 patients, 48 (9.6%) developed recurrent PE, which was fatal in 36. Of these 48 events, 39 occurred within 10 days of diagnosis and only two patients had a non‐fatal recurrent PE between 6 and 12 months. Risk factors associated with the risk for overall recurrent PE were persistent severe dyspnoea (P = 0.007), a high perfusion defect score index (PDI) (P = 0.003) and cardiopulmonary co‐morbidities (P = 0.005). Unprovoked presentation (P = 0.030), persistent severe dyspnoea (P = 0.011) and a high PDI (P = 0.001) predicted the risk for fatal PE. Overall bleeding incidence was 3.4%, no cases of bleeding occurred between 180 and 360 days post‐diagnosis. Conclusions: In spite of conventional anticoagulation, a proportion of patients with PE experience both a fatal and non‐fatal recurrent embolism within the first year. The large majority of these occur within the days proceeding diagnosis, with only a small minority occurring in the last 6 months. No bleeding was observed after 6 months. Therefore, prolonging anticoagulation for 1 year represents both a safe and effective treatment.

Diagnosis and treatment of pulmonary embolism: a multidisciplinary approach

The diagnosis of pulmonary embolism (PE) is frequently considered in patients presenting to the emergency department or when hospitalized. Although early treatment is highly effective, PE is underdiagnosed and, therefore, the disease remains a major health problem. Since symptoms and signs are non specific and the consequences of anticoagulant treatment are considerable, objective tests to either establish or refute the diagnosis have become a standard of care. Diagnostic strategy should be based on clinical evaluation of the probability of PE. The accuracy of diagnostic tests for PE are high when the results are concordant with the clinical assessment. Additional testing is necessary when the test results are inconsistent with clinical probability. The present review article represents the consensus-based recommendations of the Interdisciplinary Association for Research in Lung Disease (AIMAR) multidisciplinary Task Force for diagnosis and treatment of PE. The aim of this review is to provide clinicians a practical diagnostic and therapeutic management approach using evidence from the literature.

Venous Thromboembolism in Cancer: Frequently Asked Questions When Guidelines are Inconclusive.

ABSTRACT Management of Venous thromboembolism (VTE) in cancer patients is difficult when guidelines are inconclusive. To share a reasonable and homogeneous behavior in such circumstances, four issues, which are felt as problematic by oncologists and surgeons, have been selected; all were uncovered or only partially covered by current guidelines. Results from the literature and authors specific experience in the field were utilized to suggest reasonable solutions to the raised questions. The reported experience is the first to provide real-world management guidance for VTE in cancer patients. The effort of putting together literature review and authors experience brought to the adoption of a common behavior.

Five-year follow-up of pulmonary embolism under anticoaugulation: The PISA-PEET (Pulmonary Embolism Extension Therapy) study.

AbstractBenefits and harms of long-term anticoagulant therapy (AT) after acute pulmonary embolism (PE) are poorly known. The aim of this study was to investigate the outcome of patients with PE treated with AT for 5 years according to American College of Chest Physicians (ACCP) guidelines.Patients with both unprovoked and secondary PE were consecutively enrolled in a “real life” study. After a 12-month AT, they continued or stopped the treatment according to ACCP guidelines, and were followed-up for 5 years. Outcomes were all-cause mortality, recurrence, and fatal recurrence under AT.Of the original consecutive 585 patients, 471 were included (83 dead, 31 lost during the 1st year). Of these, 361 (76.6%) continued AT. During 5 years, death occurred in 109 (30.2%) patients, with a mortality rate of 8.00 events/100 person-years of follow-up; recurrence in 34 (9.4%), with an incidence rate of 2.58 events/person-years; fatal recurrence in 13 (3.6%), with an incidence rate of 0.95 events/person-years. The case fatality rate for recurrence was 38.2%. In the subgroup of patients with unprovoked PE, the chance of dying was significantly lower (RR 0.35; 95% confidence interval 0.24–0.53) and the tendency to fatal recurrence (not significantly) greater (0.11 events/100 person-years vs 0.07 events/100 person-years) than in the remaining patients. Major bleeding occurred in 5 (1.3%) patients. The case fatality rate for bleeding was 14.3%.During 5-year AT, 30% of patients dies, 10% experiences recurrences, and 5% has fatal recurrences. According to guidelines, most patients need to continue AT; the case fatality rate for bleeding is lower than that for recurrence.

Liver Enlargement Predicts Obstructive Sleep Apnea–Hypopnea Syndrome in Morbidly Obese Women

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is frequently present in patients with severe obesity, but its prevalence especially in women is not well defined. OSAHS and non-alcoholic fatty liver disease are common conditions, frequently associated in patients with central obesity and metabolic syndrome and are both the result of the accumulation of ectopic fat mass. Identifying predictors of risk of OSAHS may be useful to select the subjects requiring instrumental sleep evaluation. In this cross-sectional study, we have investigated the potential role of hepatic left lobe volume (HLLV) in predicting the presence of OSAHS. OSAHS was quantified by the apnea/hypopnea index (AHI) and oxygen desaturation index in a cardiorespiratory inpatient sleep study of 97 obese women [age: 47 ± 11 years body mass index (BMI): 50 ± 8 kg/m2]. OSAHS was diagnosed when AHI was ≥5. HLLV, subcutaneous and intra-abdominal fat were measured by ultrasound. After adjustment for age and BMI, both HLLV and neck circumference (NC) were independent predictors of AHI. OSAHS was found in 72% of patients; HLLV ≥ 370 cm3 was a predictor of OSAHS with a sensitivity of 66%, a specificity of 70%, a positive and negative predictive values of 85 and 44%, respectively (AUC = 0.67, p < 0.005). A multivariate logistic model was used including age, BMI, NC, and HLLV (the only independent predictors of AHI in a multiple linear regression analyses), and a cut off value for the predicted probability of OSAHS equal to 0.7 provided the best diagnostic results (AUC = 0.79, p < 0.005) in terms of sensitivity (76%), specificity (89%), negative and positive predictive values (59 and 95%, respectively). All patients with severe OSAHS were identified by this prediction model. In conclusion, HLLV, an established index of visceral adiposity, represents an anthropometric parameter closely associated with OSAHS in severely obese women.

Biomarkers and progress of antioxidant therapy for rare mitochondrial disorders

ABSTRACT Introduction: In mitochondrial disorders, a group of genetic diseases associated with decreased energy production and redox imbalance, the pathogenic role of oxidative stress has been pivotal in fostering antioxidant therapy in the attempt to modify the natural history of the conditions. Areas covered: This review focuses on oxidative stress biomarkers and discusses antioxidant treatment as a potential drug strategy for effective management of mitochondrial disorders. Expert opinion: New approaches and strategies will be needed to treat patients with mitochondrial disorders. Clinical variability of mitochondrial disorders, low sample size due to their rarity, lacking data on disease natural history and the high variance of the outcome measures so far used are all factors that, in addition to the complexity of the investigated pathway and the huge number of potential combinations of antioxidants, make it necessary to optimize treatment strategy, refine the target and improve the investigation tools. New molecules have recently been studied, such as Nrf2 inducers. Combinations of antioxidant substances also seem to have a rationale in this context. Promising results come from the stimulation of mitochondrial biogenesis or by-pass the genetic block of OXPHOS complexes by alternative enzymes NADH dehydrogenase/CoQ reductase and CoQ/O2 oxidase. Finally, gene therapy approaches seem to open interesting scenarios, targeted to repair the mutated gene to complement its defect. Going ahead with well-controlled clinical trials is still necessary to define the effectiveness of current potential therapies and to design future, hopefully more effective, interventions for mitochondrial disorders.

Lung scintigraphy in the diagnosis of pulmonary embolism: pathophysiological and practical evidence

The protean clinical presentation of pulmonary embolism (PE) is the consequence of a complex series of haemodynamic and respiratory changes caused by the impact of thrombi within the pulmonary vasculature. Haemodynamic changes result from obstruction of the pulmonary arterial bed leading to increased pulmonary vascular resistances and they are manifested clinically as dyspnoea, engorgement of neck veins, and systemic arterial hypotension. Respiratory changes are characterised by lung volume reduction, hypocapnia and hypoxaemia. Reduced lung volume is mainly due to pulmonary consolidation, atelectasis and decreased distension of the thoracic cage due to chest pain. These pathophysiological changes affect both perfusion and ventilation and could explain the low sensitivity of the ventilation/perfusion (V/Q) mismatch scintigraphic approach in diagnosing PE. Acute PE causes redistribution of pulmonary blood flow from non-perfused areas and, to a lesser extent, of ventilation; this is a further factor arguing against the use of V/Q mismatch for the scintigraphic diagnosis of the disease. Hypoxaemia is primarily the consequence of V/Q abnormalities, namely the development of areas with a low V/Q ratio. On a Q scan this can easily be appreciated from hyperperfused lung areas that, by themselves, are a marker for the scintigraphic diagnosis of PE. In conclusion, a Q scan without a V scan, when properly interpreted according to the prospective investigative study of acute pulmonary embolism diagnosis methodology (presence or absence of wedge-shaped perfusion defects) and combined with the formulation of a pre-test clinical probability, can be used in most patients with clinical suspicion of PE, reducing costs and radiation load, increasing the practicality of the examination, and providing diagnostic accuracy comparable to that of CT angiography.