Clinical Method Applied to Focused Ultrasound: The Case of Wells' Score and Echocardiography in the Emergency Department: A Systematic Review and a Meta-Analysis.

Background and Objectives: bedside cardiac ultrasound is a widely adopted method in Emergency Departments (ED) for extending physical examination and refining clinical diagnosis. However, in the setting of hemodynamically-stable pulmonary embolism, the diagnostic role of echocardiography is still the subject of debate. In light of its high specificity and low sensitivity, some authors suggest that echocardiographic signs of right ventricle overload could be used to rule-in pulmonary embolism. In this study, we aimed to clarify the diagnostic role of echocardiographic signs of right ventricle overload in the setting of hemodynamically-stable pulmonary embolism in the ED. Materials and Methods: we performed a systematic review of literature in PubMed, Web of Science and Cochrane databases, considering the echocardiographic signs for the diagnosis of pulmonary embolism in the ED. Studies considering unstable or shocked patients were excluded. Papers enrolling hemodynamically stable subjects were selected. We performed a diagnostic test accuracy meta-analysis for each sign, and then performed a critical evaluation according to pretest probability, assessed with Wells' score for pulmonary embolism. Results: 10 studies were finally included. We observed a good specificity and a low sensitivity of each echocardiographic sign of right ventricle overload. However, once stratified by the Wells' score, the post-test probability only increased among high-risk patients. Conclusions: signs of echocardiographic right ventricle overload should not be used to modify the clinical behavior in low- and intermediate- risk patients according to Wells' score classification. Among high-risk patients, however, echocardiographic signs could help a physician in detecting patients with the highest probability of pulmonary embolism, necessitating a confirmation by computed tomography with pulmonary angiography. However, a focused cardiac and thoracic ultrasound investigation is useful for the differential diagnosis of dyspnea and chest pain in the ED.

Improving the EHMRG Prognostic Evaluation of Acute Heart Failure with TAPSE/PASp: A Sequential Approach.

The Emergency Heart Failure Mortality Risk Grade (EHMRG) can predict short-term mortality in patients admitted for acute heart failure (AHF) in the emergency department (ED). This paper aimed to evaluate if TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can improve in-hospital death prediction in patients at moderate-to-high risk, according to EHMRG score classification. From 1 January 2018 to 30 December 2019, we retrospectively enrolled all the consecutive subjects admitted to our Internal Medicine Department for AHF from the ED. We performed bedside echocardiography within the first 24 h of admission. We evaluated EHMRG and NYHA in the ED, days of admission in Internal Medicine, and in-hospital mortality. We assessed cutoffs with ROC curve analysis and survival with Kaplan-Meier and Cox regression. We obtained a cohort of 439 subjects; 10.3% underwent in-hospital death. Patients with normal TAPSE/PASp in EHMRG Classes 4, 5a, and 5b had higher survival rates (100%, 100%, and 94.3%, respectively), while subjects with pathologic TAPSE/PASp had lower survival rates (81.8%, 78.3%, and 43.4%, respectively) (p < 0.0001, log-rank test). TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can further stratify the risk of in-hospital death evaluated by EHMRG.

Pre-treatment systemic immune-inflammation represents a prognostic factor in patients with advanced non-small cell lung cancer.

BACKGROUND: Inflammation plays an important role in pathogenesis, development and progression of lung cancer. The aim of the study is to assess the prognostic role of Systemic Immune-Inflammation Index (SII), obtained by analyzing the neutrophil, lymphocyte and platelet counts, and to design prognostic models for patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). METHODS: We conducted an analysis on 311 patients with advanced NSCLC, treated with first line chemo- or targeted therapy till June 2015 at our Institution. Patients were stratified in two groups with SII ≥1,270 (Group A) vs. SII <1,270 (Group B). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The best SII cutoff was identified by X-tiles program. A Cox regression model was carried out for univariate and multivariate analyses. RESULTS: At baseline, 179 patients had SII ≥1,270 (Group A), whilst 132 had lower SII (Group B). The median OS was 12.4 months in Group A and 21.7 months in Group B (P<0.001), whilst the median PFS was 3.3 and 5.2 months, respectively (P=0.029). At multivariate analysis, male gender, ECOG-PS ≥2 and SII >1,270 were predictors of worst OS, whilst IV tumor stage was only slightly significant (P=0.08). Otherwise, only wild-type EGFR status and SII ≥1,270 were independent prognostic factors for worst PFS. CONCLUSIONS: Pre-treatment SII is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies.

Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo- or targeted therapy.

BACKGROUND: We aimed to assess the prognostic role of neutrophilia, lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design models to define the prognosis of patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analysed 401 consecutive patients with advanced NSCLC treated with first line chemo- or targeted therapy. Patients were stratified into two groups with pre-treatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. RESULTS: At baseline 264 patients had NLR≥3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status and NLR≥3.7 were independent prognostic factors for worse PFS. Patients were stratified according to the presence of 0-1 prognostic factors (8%), 2-3 factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7 months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2 factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and 3.3 months respectively (p < 0.001). CONCLUSIONS: Pre-treatment NLR is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies.

Medical treatment for gastro-entero-pancreatic neuroendocrine tumours.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -ß), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.

Clinical and pathologic predictors of clinical outcome of malignant pleural mesothelioma.

AIMS AND BACKGROUND: Although worldwide use of asbestos has decreased, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next few decades. A number of scoring systems has been proposed to assess clinicopathologic features and to predict the prognosis. We assessed the relationship between patients' features and disease evolution in order to choose the best treatment able to prolong overall survival (OS) and progression-free survival (PFS). METHODS: We retrospectively analyzed patients with locally advanced or metastatic MPM, treated at the Department of Medical Oncology, Università Politecnica Marche, Italy, from January 2003 to September 2013. Data on age, sex, smoking history, asbestos exposure, performance status, tumor stage, histology, type of treatment, and routine laboratory tests including complete blood count panel, date of death, or censored status were collected. The OS and PFS were estimated using Kaplan-Meier method and Cox analysis was performed to analyze the prognostic relevance of clinical parameters. RESULTS: We enrolled a total of 62 patients. Univariate analysis showed that histologic type, performance status, response to first-line therapy, pretreatment hemoglobin levels, and plasmatic Ca125 were significant prognostic factors. Conversely, no significant correlation was found between age, sex, smoking history, reported exposure to asbestos, stages at diagnosis, treatments, and OS and PFS. CONCLUSIONS: Our results showed that anemia and increased Ca125 might be considered negative prognostic parameters in MPM patients and confirmed the prognostic role of histotype, performance status, and response to first-line chemotherapy.

Locally advanced rectal cancer: the importance of a multidisciplinary approach.

Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.