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.
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 cohort of 193 patients hospitalized with HFpEF was retrospectively studied and divided in a group with LF (N = 45), defined by a left ventricular (LV) stroke volume index (SVI) < 30 ml/m2, and a group with normal flow (N = 148). A small LV cavity was pre-defined as LV end diastolic diameter index (EDDI) below median values (<25 mm/m2 for males and <26 mm/m2 for females). Right ventricular dysfunction (RVD) was defined as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure < 0.36 mm/mmHg. An endpoint of all-cause mortality was evaluated after a median follow-up of 2.4 years.RVD (OR = 7.4; P < 0.001), atrial fibrillation (AF) during echocardiography (OR = 3.26; P = 0.008), and small LV cavity (OR = 3.81; P = 0.003) were independently associated with LF. After adjusting for age, body mass index, systolic blood pressure, renal function, chronic obstructed pulmonary disease, use of ACE inhibitors/angiotensin receptor blockers, moderate tricuspid regurgitation, RVD), LF was associated with mortality (HR = 3.69; P < 0.001) whereas the combination of the determinants of LF was not.Paradoxical LF in HFpEF is associated with small LV cavity, AF and RVD. None of the combination of different factors associated with LF could substitute direct assessment of LF status in predicting prognosis in this cohort.
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.
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.Transthoracic echocardiographic examinations of 603 patients hospitalized with HF were analyzed. In a subsample of 200 patients with HF, LV stroke volume index, LV filling pressure estimation, tricuspid annular plane systolic excursion, and systolic pulmonary artery pressure were combined to determine 4 hemodynamic profiles: normal flow-normal pressure, normal flow-high pressure, low flow without RV dysfunction, and low flow with RV dysfunction profile. This model was then applied in a validation cohort (n=403).Prognosis worsened from the normal flow-normal pressure profile to the low flow with right ventricular dysfunction profile. At the multivariate survival analysis, the model showed independent high risk-stratification capability (P<0.001), even in subgroups of patients with LVEF < or ≥50% (P=0.011 and P<0.001, respectively) and < or ≥40% (P=0.044 and P<0.001, respectively). LVEF and HF classification based on LVEF did not predict outcome.Echocardiographic-derived profiling of LV forward flow, filling pressure, and RV function allowed categorization of patients hospitalized with HF and predicted all-cause mortality independently of LVEF. This model is based on conventional echocardiography, is easy to apply, and is, therefore, suggested for clinical practice.
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