Pathophysiology of dyspnoea in acute pulmonary embolism: A cross-sectional evaluation.

BACKGROUND AND OBJECTIVE: Dyspnoea in pulmonary embolism (PE) remains poorly characterized. Little is known about how to measure intensity or about the underlying mechanisms that may be related to ventilatory abnormalities, alveolar dead space ventilation or modulating factors such as psychological modulate. We hypothesized that dyspnoea would mainly be associated with pulmonary vascular obstruction and its pathophysiological consequences, while the sensory-affective domain of dyspnoea would be influenced by other factors. METHODS: We undertook a prospective study of 90 consecutive non-obese patients (mean ± SD age: 49 ± 16 years, 41 women) without cardiorespiratory disease. All patients were hospitalized with symptoms for <15 days and a confirmed PE (multi-detector computed tomography (MDCT) scan, n = 87 and high-probability ventilation/perfusion scan, n = 3). Patients underwent assessment of dyspnoea using the Borg score, modified Medical Research Council (mMRC) scale, assessment of psychological trait, state of anxiety and depression and chest pain via the Visual Analogical Scale at the time of maximum dyspnoea. Functional evaluations such as the quantitative ventilation-perfusion lung scan, echocardiography, alveolar dead space fraction and tidal ventilation measurements were completed within 48 h of admission. RESULTS: Multivariate analyses demonstrated that dyspnoea was mainly linked to pulmonary vascular obstruction and/or its consequences such as raised pulmonary arterial pressure and chest pain. The sensory-affective domain of dyspnoea showed additional determinants such as age, depression and breathing variability. CONCLUSION: Dyspnoea is mainly related to vascular consequences of PE such as increased pulmonary arterial pressure or chest pain. The sensory-affective domain of dyspnoea also correlates with age, depression and breathing variability.

Attentional alterations in alcohol dependence are underpinned by specific executive control deficits.

BACKGROUND: Attentional biases and deficits play a central role in the development and maintenance of alcohol dependence, but the underlying attentional processes accounting for these deficits have been very little explored. Importantly, the differential alterations across the 3 attentional networks (alerting, orienting, and executive control) remain unclear in this pathology. METHODS: Thirty recently detoxified alcohol-dependent individuals and 30 paired controls completed the Attention Network Test, which allow exploring the attentional alterations specifically related to the 3 attentional networks. RESULTS: Alcohol-dependent individuals presented globally delayed reaction times compared to controls. More centrally, they showed a differential deficit across attention networks, with a preserved performance for alerting and orienting networks but impaired executive control (p < 0.001). This deficit was not related to psychopathological comorbidities but was positively correlated with the duration of alcohol-dependence habits, the number of previous detoxification treatments and the mean alcohol consumption before detoxification. CONCLUSIONS: These results suggest that attentional alterations in alcohol dependence are centrally due to a specific alteration of executive control. Intervention programs focusing on executive components of attention should be promoted, and these results support the frontal lobe hypothesis.

Lower-limb drainage mapping for lymphedema risk reduction after pelvic lymphadenectomy for endometrial cancer.

OBJECTIVES: Pelvic lymphadenectomy is associated with a significant risk of lower-limb lymphedema. In this proof-of-concept study, we evaluated the feasibility of identifying the lower-limb drainage nodes (LLDNs) during pelvic lymphadenectomy for endometrial cancer. Secondary objectives were to map lower-limb drainage and to assess the diagnostic value of our mapping technique. METHODS: This prospective study included patients with endometrial cancer requiring pelvic lymphadenectomy, without neoadjuvant radiotherapy or chemotherapy and without history of lower-limb surgery. A radiopharmaceutical was injected into both feet on the day before surgery. LLDNs were identified using preoperative lymphoscintigraphy and intraoperative isotopic probe detection, then removed before complete pelvic lymphadenectomy. LLDNs and pelvic lymphadenectomy specimens underwent separate histological analysis. RESULTS: Of the 12 patients with early-stage endometrial cancer, 10 underwent preoperative lymphoscintigraphy, which consistently identified inguinal, femoral, and pelvic LLDNs (detection rate: 100%). The intraoperative detection rate was 83% (10/12). Median number of hot nodes per patient was 5 nodes (range: 3-7) on the right and 3 nodes (range: 2-6) on the left. Of 107 LLDNs, 106 were in the external iliac area, including 38 in the lateral group and 45 in the intermediate and medial groups. None of the patients had node metastases at any site. No early complications related to the technique occurred. CONCLUSION: Our mapping technique appears feasible, safe, and associated with a high LLDN identification rate. LLDN mapping may allow the preservation of LLDNs, thereby decreasing the risk of lower-limb lymphedema and improving quality of life.

Optimizing and developing a scalable, chemically defined, animal component-free lentiviral vector production process in a fixed-bed bioreactor.

Lentiviral vectors (LVVs) play a critical role in gene delivery for ex vivo gene-modified cell therapies. However, the lack of scalable LVV production methods and the high cost associated with them may limit their use. In this work, we demonstrate the optimization and development of a scalable, chemically defined, animal component-free LVV production process using adherent human embryonic kidney 293T cells in a fixed-bed bioreactor. The initial studies focused on the optimization of the culture process in 2D static cultures. Process changes such as decreasing cell seeding density on day 0 from 2.5 × 104 to 5 × 103 cells/cm2, delaying the transient transfection from 24 to 120 h post-seeding, reducing plasmid DNA to 167 ng/cm2, and adding 5 mM sodium butyrate 6 h post-transfection improved functional LVV titers by 26.9-fold. The optimized animal component-free production process was then transferred to the iCELLis Nano bioreactor, a fixed-bed bioreactor, where titers of 1.2 × 106 TU/cm2 were achieved when it was operated in perfusion. In this work, comparable functional LVV titers were obtained with FreeStyle 293 Expression medium and the conventional Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum both at small and large scale.

Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography?

PURPOSE: To evaluate the rate of positive, negative, and indeterminate results and the agreement between initial and expert readings for lung scintigraphy and computed tomographic (CT) angiography performed in patients suspected of having pulmonary embolism (PE) during pregnancy. MATERIALS AND METHODS: Institutional review board approval was obtained. The authors retrospectively analyzed the images from lung scintigraphy and CT angiography performed in pregnant patients during the past 9 years. Images from 46 CT angiographic examinations performed in 43 patients and 91 of 94 lung scintigraphic examinations were reviewed by experts, whose readings were then compared with the initial reports. For CT angiography, the quality of opacification was graded as good, suboptimal, or poor and intraarterial attenuation was measured. RESULTS: The rates of positive findings (seven of 43 patients [16%] with CT angiography and 10 of 91 patients [11%] with scintigraphy, P = .36), negative findings (28 of 43 patients [65%] with CT angiography and 64 of 91 patients [70%] with scintigraphy, P = .54), and indeterminate findings (eight of 43 patients [19%] with CT angiography and 17 of 91 patients [19%] with scintigraphy, P = .99) were similar for CT angiography and lung scintigraphy. There were four discrepancies between initial and expert readings for CT angiography (κ = 0.84; confidence interval: 0.68, 0.99) and 14 for lung scintigraphy (κ = 0.75; 95% confidence interval: 0.63, 0.87). Opacification was classified as good for only 23 of the 46 CT angiographic examinations (50%). Attenuation values were significantly different among the groups with good, suboptimal, or poor opacification. Alternative diagnoses unsuspected at chest radiography were demonstrated at CT angiography in five of the 43 patients (12%). The mean maternal radiation dose was 0.9 mSv for lung scintigraphy and 7.3 mSv for CT angiography. CONCLUSION: Lung scintigraphy and CT angiography have comparable performances for PE diagnosis during pregnancy. Interobserver agreement is better for CT angiography, which also enables alternative diagnosis of unsuspected disease but delivers higher maternal radiation dose.

Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection.

BACKGROUND: The objective of axillary reverse mapping (ARM) is to preserve the main lymphatic chain-with both the nodes and the ducts-in relation to lymphatic arm drainage (LAD) during an axillary dissection (AD). METHODS: From July 2006 to March 2008, 23 patients with stage II or III breast carcinoma requiring an AD underwent an ARM procedure. Identification of the ARM nodes relied on an isotope injection into the web space of the ipsilateral hand. During AD, the radioactive ARM node was localized above the second intercostal brachial nerve, and blue dye was directly injected inside the node to visualize the efferent ducts, constituting the lymphatic ARM chain. The blue and radioactive nodes constituted the ARM sampling, while other nodes were considered part of the AD. RESULTS: Metastatic lymph node involvement was identified in the AD in 20 of 23 patients, with an average of 4.4 (1-11) nodes involved and an average of 10.7 (7-20) lymph nodes removed. The ARM sampling was performed in 21 of 23 patients (91%), with an average of 1.6 ARM nodes removed. In 18 of these 21 patients (86%), the nodes relating to ARM sampling had no metastatic involvement. There were 3 patients (14%) who demonstrated metastatic involvement of the ARM sampling, and all had pN3a (N+ > 9) involvement of the axilla. CONCLUSION: This technique of combined isotopic and blue dye ARM and findings must now be validated. A multicentric study is planned to confirm this data.

Effectiveness of a Functional Rehabilitation Program After Bariatric Surgery: a Pilot Study.

BACKGROUND: Beyond obesity-related comorbidities, overweight patients have a high risk of developing osteoarticular pathologies. Moreover, weight loss following bariatric surgery induces a decrease in fat mass but also in muscle mass, thus affecting the physical capacities of these patients. Functional rehabilitation is a solution to correct these imbalances. The aim of this study was to evaluate the effectiveness of a functional rehabilitation program after bariatric surgery. METHODS: Twenty-three patients with severe obesity (BMI = 37.9 ± 5.7 kg/m2; 41.1 ± 12.9 years) participated in a functional rehabilitation protocol, 2 months after sleeve gastrectomy. Rehabilitation program consisted of 20 sessions of 1h30 (two sessions per week), based on endurance training, muscle strengthening, and proprioception work. An initial and final assessment included bioelectrical impedance measurements, questionnaires, and physical function tests. RESULTS: All impedance parameters were significantly improved in 20 sessions: % excess weight loss (%EWL) from 27.6 ± 9.1 to 51.1 ± 13.4% and % fat-free mass from 52.7 ± 5.6 to 57.6 ± 6.7%. Waist and hip circumferences were significantly reduced in 20 sessions: from 107.4 ± 13.7 to 94.5 ± 12.6 cm and from 120.5 ± 12.4 to 108.7 ± 11.7 cm, respectively (p < 0.001). Physical function tests were significantly improved between the 1st and the 20th sessions (p < 0.001). The cycloergometer stress test progressed from 77.7 ± 24.1 to 93.6 ± 27.2 W, and the sit-to-stand test from 20 ± 5.2 to 24.8 ± 7.6 flexions in 30 s. The Quality Of Life, Obesity and Dietetics (QOLOD) scale increased by 12.6%. CONCLUSIONS: The functional rehabilitation protocol of 20 sessions significantly improved patients' body composition, functional tests, and quality of life. The standardization of tests and sessions allowed to objectively assess progress.

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism. A single center cohort study.

INTRODUCTION: Up to 50% of patients with pulmonary embolism (PE) present lung perfusion defects after six months of anticoagulant treatment, suggesting residual pulmonary vascular obstruction (RPVO). The risk of recurrence in patients with RPVO remains unknown. The present study aims to assess the risk of recurrent venous thromboembolism (VTE) in patients with RPVO after a first symptomatic episode of PE. METHODS: Consecutive patients who survived a first objectively proven acute PE, treated for at least three months with anticoagulants, were included and followed prospectively. RPVO was defined as a pulmonary vascular obstruction of >10% on ventilation/perfusion lung scan performed at inclusion. Objectively proven VTE recurrences were registered and confirmed by an investigator unaware of the result of the ventilation/perfusion lung scan. RESULTS: Among the 310 patients (median age: 61years) included in the study, 60 (19%) had RPVO. During a median follow-up of 51.3months, 66 patients (21.2%, 95% CI [17.5-26.7]) experienced recurrent VTE. In an adjusted cox proportional hazards analysis, we identified RPVO (HR 1.94; 95% CI [1.11-3.39]; p=0.026) and unprovoked PE (HR 3.56; 95% CI [1.79-7.07]; p=0.00051) as independent risk factors for recurrent VTE whereas extended anticoagulation therapy (HR 0.19; 95% CI [0.07-0.55]; p=0.00014) was associated with a low risk of recurrence. CONCLUSION: The results suggest that RPVO is an independent risk factor of recurrent VTE after a first PE.

[FDG (18 fluorodeoxyglucose) positron emission tomography and breast cancer]. / Tomographie par emission de positons (TEP) au FDG et cancer du sein.

Positron emission tomography (PET) is a metabolic radionuclide imaging method in which a tracer labeled with a positron emitter is detected with a dedicated system. 18F-fluorodeoxyglucose (FDG) accumulates in tumor cells because of their increased glycolytic activity, and is thus widely used as a tracer in oncology. This increased metabolic activity precedes morphologic modifications, making FDG-PET a very useful tool for detecting and staging cancer. It can also be used to characterize morphologic changes, differentiating not only between benign and malignant lesions, but also between viable tumor cells and areas of necrosis and/or fibrosis induced by treatments. Being a whole-body examination, it allows malignancies to be staged in a single procedure. Systems combining PET and CT (computed tomography) offer improved performance, providing both metabolic and anatomical data. This technique appears to be useful for initial breast cancer staging, especially of locally advanced forms and suspected recurrences (increase of isolated tumor marker). Early studies of PET evaluation of responses to hormonal and/or cytotoxic therapies have also given very promising results. However, this technique does not seem sufficiently sensitive to be included in the initial screening or diagnosis of primary tumors, owing to its limited resolution (about 5 mm) and its restricted availability. This approach is poorly sensitive when used for axillary assessment, but offers good specificity.

Maladaptive social self-beliefs in alcohol-dependence: a specific bias towards excessive high standards.

BACKGROUND: Emotional and interpersonal impairments associated with alcohol-dependence have been recently explored, but the distorted cognitive representations underlying these deficits remain poorly understood. The present study aims at exploring the presence of maladaptive social self-beliefs among alcohol-dependent individuals, as these biased self-beliefs have been recently shown to play a crucial role in the development and maintenance of other psychopathological states (social anxiety and depression). METHODOLOGY/PRINCIPAL FINDINGS: Twenty-five recently detoxified alcohol-dependent participants and 25 matched controls filled in self-report questionnaires evaluating maladaptive social self-beliefs, interpersonal problems and several comorbid states (anxiety, social anxiety, depression). As compared to controls, alcohol-dependent individuals showed higher scores than controls for the three subcategories of maladaptive social self-beliefs (high standards, conditional beliefs and unconditional beliefs). Our key finding was that when comorbidities were controlled for, alcohol-dependence was associated with a specific bias towards exaggerated high standards in social contexts. Moreover, these high standards beliefs were strongly correlated with interpersonal problems. CONCLUSIONS/SIGNIFICANCE: These results provide the first insights into the influence of cognitive biases on interpersonal problems in addictive states, and suggest that maladaptive self-beliefs could have a central influence on the development and maintenance of alcohol-dependence.