Multifactorial Evaluation following Cytoreductive Surgery for Malignant Pleural Mesothelioma in Patients with High Symptom-Burden.

Mesothelioma has a scant prognosis and a great impact on symptoms and the quality of life. Pleurectomy/decortication and extrapleural pneumonectomy are the two cytoreductive surgical strategies, with different invasiveness, but achieving similar oncological results. Hereafter, the two surgical procedures effects on symptoms and the quality of life are compared in a high symptom-burden population. Between 2003 and 2017, 55 consecutive patients underwent pleurectomy/decortication (n = 26) or extrapleural pneumonectomy (n = 29), both followed by adjuvant chemo-radiotherapy. Cardio-pulmonary function, symptoms and the quality of life (Short-Form-36 and St.George's questionnaires) were evaluated pre- and 3-, 6-, 12- and 24-months postoperatively. Extrapleural pneumonectomy demonstrated lower pain at 12 months but a higher decrement of forced vital capacity at 24 months than pleurectomy/decortication. Both procedures revealed a 3-months improvement of many symptoms and the quality of life determinants. Improvement in physical, social and pain-related measured parameters lasted for a longer time-spawn in the extrapleural pneumonectomy group. No differences were found in chemotherapy compliance and survival between groups. Age-at-presentation (p = 0.02) and non-epitheliod histology (p = 0.10) were the only significant prognosticators. Surgery, despite poor survival results, improved symptoms and the quality of life in patients with mesothelioma with high symptom-burden at diagnosis. Therefore, extrapleural pneumonectomy demonstrated the most durable effects.

Trauma in pregnancy clinical practice guidelines: systematic review.

PURPOSE: To objectively evaluate the methodological quality and clinical heterogeneity robustness of the published clinical practice guidelines (CPGs) on the management of trauma in pregnancy. MATERIALS AND METHODS: Pubmed, Google Scholar, UpToDate, and Scopus Database were searched. The risk of bias and quality assessment of the included CPGs were performed using "The Appraisal Of Guidelines for Research and Evaluation (AGREE II)" tool. The following points relating to the management of trauma during pregnancy were addressed: quality of evidence assessment, classification of recommendations, main causes of trauma in pregnancy, importance of correct use of seat belts, ultrasound scans and/or pregnancy test in every female of reproductive age, description of physiological changes in pregnancy, classification in primary and secondary survey, primary survey based on ABCD Approach, fetus viable based on the weeks, radiographic studies for maternal evaluation, duration of fetal monitoring, use of anti-D immunoglobulin in rhesus-D-negative pregnant trauma patients, description of dose of RhD-Ig, the way to define gestational age if it was undetermined, descriptions of obstetrical complications, use of tetanus vaccination, and timing to perimortem cesarean section (CS). RESULTS: Six CPGs were included. Quality of evidence assessment was described in 16.7% of CPGs (1/6), while it was not reported in 83.3% (5/6). Classification of recommendations was reported in 50% (3/3) of the CPGs. Motor vehicle crash was reported as the main cause of trauma in pregnancy in all the CPGs included in the present review, despite that the importance of a correct use of seat belts was described only in the 50% (3/6). Definition of fetal viability was also different among the included CPGs; in 50% (3/6) defined a fetus viable when it from 23 weeks, 33.3% (2/6) from 24 weeks, and 16.7% (1/6) from 20 weeks of gestation. Regarding the type of fetal monitoring, 33.3% (2/6) CPGs recommended CTG assessment at least every 4 h, 16.7% (1/6) at least every 6 h, 33.3% for 24 h if there are not reassuring signs and 16.7% (1/6) did not specify the duration of monitoring. Recommendations about the use of anti-D-immunoglobulin in rhesus-D-negative pregnant were also heterogeneous: 50% (3/6) of the CPGs suggested administration in all rhesus-D-negative pregnant women, 16.7% (1/6) only according to gestational age at trauma or in case of significant abdominal trauma, and 16.7% (1/6) only in case of positive Kleihauer test while 16.7% (1/6) did not specify it. Administration of tetanus vaccination was suggested in in 33.3% (2/6) of CPGs. Finally, there were different descriptions of timing to perimortem CS: 33.3% (2/6) of CPGs claims to do CS no later than 4 min, 50% (3/6) no later than 5 min, and 16.7% (1/6) does not describe timing for CS. The AGREE II standardized domain scores for the first overall assessment (OA1) had a mean of 69%. Only three CPGs scored more than 60% and revealed a consensus agreement between the reviewers on recommending the use of these CPGs. CONCLUSION: There is clinical heterogeneity in some of the most relevant aspects of the management of pregnant women with trauma. The findings from this systematic review highlight the need for up to date and shared guidelines promoted by the main body societies in order make management of pregnant women with trauma homogenous.

Major discrepancies between what clinical trial registries record and paediatric randomised controlled trials publish.

BACKGROUND: Whether information from clinical trial registries (CTRs) and published randomised controlled trial (RCTs) differs remains unknown. Knowing more about discrepancies should alert those who rely on RCTs for medical decision-making to possible dissemination or reporting bias. To provide help in critically appraising research relevant for clinical practice we sought possible discrepancies between what CTRs record and paediatric RCTs actually publish. For this purpose, after identifying six reporting domains including funding, design, and outcomes, we collected data from 20 consecutive RCTs published in a widely read peer-reviewed paediatric journal and cross-checked reported features with those in the corresponding CTRs. METHODS: We collected data for 20 unselected, consecutive paediatric RCTs published in a widely read peer-reviewed journal from July to November 2013. To assess discrepancies, two reviewers identified and scored six reporting domains: funding and conflict of interests; sample size, inclusion and exclusion criteria or crossover; primary and secondary outcomes, early study completion, and main outcome reporting. After applying the Critical Appraisal Skills Programme (CASP) checklist, five reviewer pairs cross-checked CTRs and matching RCTs, then mapped and coded the reporting domains and scored combined discrepancy as low, medium and high. RESULTS: The 20 RCTs were registered in five different CTRs. Even though the 20 RCTs fulfilled the CASP general criteria for assessing internal validity, 19 clinical trials had medium or high combined discrepancy scores for what the 20 RCTs reported and the matched five CTRs stated. All 20 RCTs selectively reported or failed to report main outcomes, 9 had discrepancies in declaring sponsorship, 8 discrepancies in the sample size, 9 failed to respect inclusion or exclusion criteria, 11 downgraded or modified primary outcome or upgraded secondary outcomes, and 13 completed early without justification. The CTRs for seven trials failed to index automatically the URL address or the RCT reference, and for 12 recorded RCT details, but the authors failed to report the results. CONCLUSIONS: Major discrepancies between what CTRs record and paediatric RCTs publish raise concern about what clinical trials conclude. Our findings should make clinicians, who rely on RCT results for medical decision-making, aware of dissemination or reporting bias. Trialists need to bring CTR data and reported protocols into line with published data.

Aortopathy in Marfan syndrome: an update.

Marfan syndrome (MFS) is an inherited autosomal dominant multisystem disease caused by mutations in the FBN1 gene encoding fibrillin-1, an extracellular matrix glycoprotein widely distributed in mesenchymal-derived tissues that provide a scaffold for elastin deposition. MFS is characterized by variable clinical manifestations, including skeletal, ocular, and cardiovascular abnormalities; ascending aortic aneurysm with ensuing dissection and rupture is the main life-threatening cardiovascular manifestation of MFS. Histological aspects of MFS aortopathy include a medial degeneration from disarray and fragmentation of elastic fibers and accumulation of basophilic ground substance areas depleted of smooth muscle cells (SMCs). Transmission electron microscopy well evidences the high number of interruptions and the thick appearance of the elastic lamellae and the accumulation of abundant extracellular glycosaminoglycan-rich material, sometimes SMCs showing a prevalent synthetic phenotype. The aberrant signaling of transforming growth factor-ß (TGF-ß) as the consequence of the altered structure of fibrillin-1 induces activation and the overexpression of Smad-dependent profibrotic signaling pathway and ERK1/2-mediated increased synthesis of matrix metalloproteinases. In addition, MFS is accompanied by an impaired aortic contractile function and aortic endothelial-dependent relaxation, which is caused by an enhancement of the oxidative stress and increased reactive oxygen species during the progression of the disease. Many studies are currently evaluating the contribution of TGF-ß-mediated biomolecular pathways to the progression of MFS aortopathy and aneurysm development, in order to discover new targets for pharmacological strategies aimed to counteract aortic dilation.