Liver progenitor cell markers correlate with liver damage and predict short-term mortality in patients with alcoholic hepatitis

Alcoholic hepatitis (AH) is a severe condition developed in patients with underlying alcoholic liver disease. Ductular reaction has been associated with chronic alcohol consumption but there is no information regarding the extent of liver progenitor cell (LPC) proliferation in AH. The aim of this study was to investigate LPC markers in AH and its correlation with disease severity. Fifty-nine patients with clinical and histological diagnosis of AH were included in the study. LPC markers were assessed by real-time polymerase chain reaction (PCR) and immunohistochemistry. Standard logistic regression analysis and classification and regression trees (CART) analysis were used for statistical analysis. A microarray analysis showed an up-regulation of LPC markers in patients with AH. Real-time PCR demonstrated that epithelial cell adhesion molecule (EpCAM), Prominin-1, and Keratin7 were significantly increased in patients with AH compared with normal livers (P ≤ 0.01), chronic hepatitis C (P ≤ 0.01), and HCV-induced cirrhosis (P ≤ 0.01). Immunohistochemistry scores generated for Keratin7 and EpCAM demonstrated a good correlation with gene expression. Keratin7 gene expression correlated with liver failure as assessed by model for endstage liver disease score (r = 0.41, P = 0.006) and Maddrey's discriminant function (r = 0.43, P = 0.004). Moreover, Keratin7 (OR1.14, P = 0.004) and Prominin-1 (OR1.14, P = 0.002), but not EpCAM (OR1.16, P = 0.06), were identified as independent predictors of 90-day mortality. CART analysis generated an algorithm based on the combination of Keratin7 and EpCAM gene expression that stratified three groups of patients with high, intermediate, and low short-term mortality (89%, 33%, and 6%, respectively; area under the receiver operating curve 0.73, 95% confidence interval 0.60-0.87). Keratin7 expression provided additional discrimination potential to the age, bilirubin, international normalization ratio, creatinine (ABIC) score. CONCLUSION: LPC markers correlate positively with severity of liver disease and short-term mortality in AH patients. This study suggests that LPC proliferation may be an important feature of AH pathophysiology.     

Preservación de órgano tras un tratamiento con quimioterapia de inducción en pacientes con carcinomas localmente avanzados (T3-T4) de cavidad oral y orofaringe

Introduction and objectivesWith the goal of achieving functional preservation, one of the treatment strategies for patients with locally advanced squamous cell carcinomas of the head and neck is to initiate treatment with induction chemotherapy (CT) and decide the second therapeutic manoeuvre depending on the response. The objective of this study is to evaluate organ preservation capacity based on this therapeutic approach in patients with tumours of the oral cavity and oropharynx.MethodsA retrospective study of 246 patients with locally advanced carcinomas of the oral cavity or oropharynx (cT3-T4) initially treated with induction CT.ResultsAfter induction CT 28% of patients achieved a complete response of the primary location of the tumour, 43.1% a partial response greater than 50%, and 28.9% a reduction less than 50% or persistence. After the induction CT treatment 70 patients (28.5%) underwent surgical treatment, and 176 (71.5%) radiotherapy (RT) or chemoradiotherapy (CRT). Considering the patients treated non-surgically (n = 176), organ preservation for patients with a complete response (n = 66) was 65.2%, for those patients with a partial response greater than 50% (n = 75) it was 30.7%, and for patients with a partial response less than 50% or persistence (n = 35) it was 14.3%.ConclusionThe response to treatment with induction CT has prognostic value in patients with locally advanced carcinomas of the oral cavity and oropharynx. Patients who are candidates for conservative treatment with RT or CRT would be those who achieve a complete response after induction treatment.     

Preservación de órgano en pacientes con tumores avanzados de laringe. Resultados de la quimioterapia de inducción versus quimio-radioterapia en la práctica clínica real

Introduction and objectivesA high percentage of patients with locally advanced larynx carcinomas are candidates for inclusion in organ preservation protocols. The objective of this study is to compare the results of two schemes of preservation, induction chemotherapy versus chemoradiotherapy, in patients with locally advanced larynx carcinomas in the context of actual clinical practice.MethodsOur retrospective study included 157 patients with locally advanced tumours of the larynx (T3-T4) treated with induction chemotherapy (n = 121) or chemoradiotherapy (n = 36).ResultsFrom 121 patients who began treatment with induction chemotherapy, 6 died due to toxicity, 37 were treated with surgery, and 78 completed the preservation scheme; 36 patients received treatment with chemoradiotherapy. There were no significant differences in 5-year disease-specific survival between both treatments: 68.9% in induction chemotherapy versus 75.7% in chemoradiotherapy (p = 0.259). In 45.9% of patients the laryngeal function was preserved. Patients treated with chemoradiotherapy had a tendency to have better 5-year laryngeal dysfunction-free survival than patients treated with induction chemotherapy (55.6% versus 44.8%, p = 0.079).ConclusionPatients included in a protocol of organ preservation achieved a 5-year laryngeal dysfunction-free survival of 45.9%. There were no significant differences in disease-specific survival among patients treated with induction chemotherapy or chemoradiotherapy.     

Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants

The aim of this study was to assess whether prematurely born infants have a genetic predisposition to respiratory syncytial virus (RSV) infection-related respiratory morbidity. One hundred and forty-six infants born at less than 36 weeks of gestation were prospectively followed. Nasopharygeal aspirates were obtained on every occasion the infants had a lower respiratory tract infection (LRTI) regardless of need for admission. DNA was tested for 11 single-nucleotide polymorphisms (SNPs). Chronic respiratory morbidity was assessed using respiratory health-related questionnaires, parent-completed diary cards at a corrected age of 1 year and review of hospital notes. Lung function was measured at a post menstrual age (PMA) of 36 weeks and corrected age of 1 year. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36-week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (interleukin 10 (IL10), nitric oxide synthase 2A (NOS2A), surfactant protein C (SFTPC), matrix metalloproteinase 16 (MMP16) and vitamin D receptor (VDR)) and reduced lung function at 1 year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs. Conclusions: Our results suggest that prematurely born infants may have a genetic predisposition to RSV LRTIs and subsequent respiratory morbidity which is independent of premorbid lung function.