Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review

: Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of the head and neck region, with a poor survival rate (5-year overall survival 50-80%) as a consequence of an advanced-stage diagnosis and high recurrence rate. Tobacco smoking and alcohol abuse are the main risk factors of LSCC development. An early diagnosis of LSCC, a prompt detection of recurrence and a more precise monitoring of the efficacy of different treatment modalities are currently needed to reduce the mortality. Therefore, the identification of effective diagnostic and prognostic biomarkers for LSCC is crucial to guide disease management and improve clinical outcomes. In the past years, a dysregulated expression of small non-coding RNAs, including microRNAs (miRNAs), has been reported in many human cancers, including LSCC, and many miRNAs have been explored for their diagnostic and prognostic potential and proposed as biomarkers. We searched electronic databases for original papers that were focused on miRNAs and LSCC, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. According to the outcome, 566 articles were initially screened, of which 177 studies were selected and included in the analysis. In this systematic review, we provide an overview of the current literature on the function and the potential diagnostic and prognostic role of tissue and circulating miRNAs in LSCC

Left ventricular output indices in hospitalized heart failure: when "simpler" may not mean "better"

Assessment of left ventricular (LV) output in hospitalized patients with heart failure (HF) is important to determine prognosis. Although echocardiographic LV ejection fraction (EF) is generally used to this purpose, its prognostic value is limited. In this investigation LV-EF was compared with other echocardiographic per-beat measures of LV output, including non-indexed stroke volume (SV), SV index (SVI), stroke distance (SD), ejection time (ET), and flow rate (FR), to determine the best predictor of all-cause mortality in patients hospitalized with HF. A final cohort of 350 consecutive patients hospitalized with HF who underwent echocardiography during hospitalization was studied. At a median follow-up of 2.7\ua0years, 163 patients died. Non-survivors at follow-up had lower SD, SVI and SV, but not ET, FR and LV-EF than survivors. At multivariate analysis, only age, systolic blood pressure, chronic kidney disease, chronic obstructive pulmonary disease, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SVI remained significantly associated with outcome [HR for SVI 1.13 (1.04-1.22), P\u2009=\u20090.003]. In particular, for each 5\ua0ml/m2 decrease in SVI, a 13% increase in risk of mortality for any cause was observed. SVI is a powerful prognosticator in HF patients, better than other per-beat measures, which may be simpler but partial or incomplete descriptors of LV output. SVI, therefore, should be considered for the routine echocardiographic evaluation of patients hospitalized with HF to predict prognosis

Echocardiographic Evaluation of Left Ventricular Output in Patients with Heart Failure: A Per-Beat or Per-Minute Approach?

Left ventricular (LV) output is a predictor of adverse outcome in patients with heart failure. It can be evaluated using a per-beat approach, measuring stroke volume index (SVI), or a per-minute approach, calculating cardiac index (CI). However, the prognostic value of these two approaches has never been compared

Novel Echocardiographic Approach to Hemodynamic Phenotypes Predicts Outcome of Patients Hospitalized With Heart Failure

Although in clinical practice heart failure (HF) patients are classified using left ventricular ejection fraction (LVEF), this categorization is insufficient for prognosis, especially when LVEF is preserved or there is a concomitant right ventricular (RV) dysfunction. We hypothesized that a combined noninvasive evaluation of LV forward flow, filling pressure, and RV function would be better than LVEF in predicting all-cause mortality of hospitalized patients with HF

Right Atrial Pressure Is Associated with Outcomes in Patients with Heart Failure and Indeterminate Left Ventricular Filling Pressure

In a significant proportion of patients with left-sided heart failure (HF), left ventricular filling pressure (LVFP) may not be estimated using echocardiography, so filling pressure status may remain indeterminate. In these patients, mean right atrial pressure (mRAP) has been suggested as a surrogate of LVFP. The aim of this study was to determine whether high mRAP has prognostic value in patients with HF with indeterminate pressure (IP) and whether mRAP-based reclassification of patients with IP has an impact on outcomes

Paradoxical low-flow phenotype in hospitalized heart failure with preserved ejection fraction

Low flow (LF) in heart failure with preserved ejection fraction (HFpEF) is a paradox but is associated with worse prognosis. Determinants of LF in HFpEF have not been clarified but their assessment could corroborate recognition and definition of such a paradoxical condition

A Systematic Review of Diagnostic and Prognostic Biomarkers for Head and Neck Cancer of Unknown Primary: An Unmet Clinical Need

Head and neck cancer of unknown primary (HNCUP) is defined as cervical lymph node metastases without a detectable primary tumor. The management of these patients presents a challenge to clinicians since guidelines in the diagnosis and treatment of HNCUP remain controversial. An accurate diagnostic workup is fundamental for the search for the hidden primary tumor to allow the best adequate treatment strategy. The purpose of this systematic review is to present the currently available data about the diagnostic and prognostic molecular biomarkers for HNCUP. Systematic research in an electronic database was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and identified 704 articles, of which 23 studies were selected and included in the analysis. Fourteen studies investigated HNCUP diagnostic biomarkers and focused on the human papilloma virus (HPV) and the Epstein–Barr virus (EBV) due to the strong associations with oropharyngeal cancer and nasopharyngeal cancer, respectively. HPV status was shown to possess prognostic value, correlating with longer disease-free survival and overall survival. HPV and EBV are the only available HNCUP biomarkers, and they are already used in clinical practice. A better characterization of the molecular profiling and the development of tissue-of-origin classifiers are necessary to improve the diagnosis, staging, and therapeutic management of patients with HNCUP

Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review

Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of the head and neck region, with a poor survival rate (5-year overall survival 50–80%) as a consequence of an advanced-stage diagnosis and high recurrence rate. Tobacco smoking and alcohol abuse are the main risk factors of LSCC development. An early diagnosis of LSCC, a prompt detection of recurrence and a more precise monitoring of the efficacy of different treatment modalities are currently needed to reduce the mortality. Therefore, the identification of effective diagnostic and prognostic biomarkers for LSCC is crucial to guide disease management and improve clinical outcomes. In the past years, a dysregulated expression of small non-coding RNAs, including microRNAs (miRNAs), has been reported in many human cancers, including LSCC, and many miRNAs have been explored for their diagnostic and prognostic potential and proposed as biomarkers. We searched electronic databases for original papers that were focused on miRNAs and LSCC, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. According to the outcome, 566 articles were initially screened, of which 177 studies were selected and included in the analysis. In this systematic review, we provide an overview of the current literature on the function and the potential diagnostic and prognostic role of tissue and circulating miRNAs in LSCC

Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas

Intraductal neoplasms are important precursors to invasive pancreatic cancer and an opportunity to detect and treat pancreatic neoplasia before an invasive carcinoma develops. The diagnostic evaluation of these lesions is challenging as diagnostic imaging and cytological sampling do not provide accurate information on lesion classification, the grade of dysplasia or the presence of invasion. Moreover, the molecular driver gene mutations of these precursor lesions have yet to be fully characterized. Fifty-two intraductal papillary neoplasms, including 48 intraductal papillary mucinous neoplasms (IPMNs) and 4 intraductal tubulopapillary neoplasms (ITPNs), were subjected to the mutation assessment in 51 cancer-associated genes, using Ion Torrent semiconductor-based next-generation sequencing. P16 and Smad4 immunohistochemistry was performed on 34 IPMNs, and 17 IPMN-associated carcinomas. At least one somatic mutation was observed in 46/48 (96%) IPMNs; 29 (60%) had multiple gene alterations. GNAS and/or KRAS mutations were found in 44/48 (92%) of IPMNs. GNAS was mutated in 38/48 (79%) IPMNs, KRAS in 24/48 (50%), and these mutations coexisted in 18/48 (37.5%) of IPMNs. RNF43 was the third most commonly mutated gene and was always associated with GNAS and/or KRAS mutations, as were virtually all the low frequency mutations found in other genes. Mutations in TP53 and BRAF genes (10% and 6%) were only observed in high-grade IPMNs. P16 was lost in 7/34 IPMNs and 9/17 IPMN-associated carcinomas; Smad4 was lost in 1/34 IPMN and 5/17 IPMN-associated carcinomas. In contrast to IPMNs, only one of four ITPN had detectable driver gene (GNAS and NRAS) mutations. Deep sequencing DNA from 7 cyst fluid aspirates identified 10 of the 13 mutations detected in their associated IPMN. Using next-generation sequencing to detect cyst fluid mutations has the potential to improve the diagnostic and prognostic stratification of pancreatic cystic neoplasms