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Impaired arterial oxygenation, ranging from increased alImpaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo 2 ) to hypoxemia, is veolar-arterial oxygen gradient (AaDo 2 ) to hypoxemia, is comcommonly reported in patients with cirrhosis. 1 In the absence monly present in patients with cirrhosis. Nitric oxide (NO), of overt mechanical dysfunction of the lung, it has been through pulmonary vasodilatation, may play a major role in suggested that oxygenation abnormalities of cirrhotic pathe oxygen abnormalities of cirrhosis. Our aim was to study tients may be a consequence of ventilation/perfusion misthe relationship between NO production and O 2 abnormalities match and intrapulmonary shunting. 2-4 Intrapulmonary vasin 45 nonsmoking patients with cirrhosis and without major cular dilatations and artero-venous communications are cardiovascular and respiratory diseases. Intrapulmonary thought to be the pathological bases of the physiological shunting was detected by contrast-enhanced (CE) echocardimechanisms of oxygenation abnormalities. 5,6 ography. Lung volumes and diffusion, arterial blood gas analy-The vascular dilatations can result in severe hypoxemia, sis, serum NO 0 2 /NO 0 3 , NO output in the exhaled air, and which, at variance from that caused by intrapulmonary cardiac index by the echocardiographic method were detershunts, may respond normally to supplemental oxygen. mined in all patients. Twenty-seven (60%) patients had anIncreased circulation of a pulmonary vasodilator seems abnormally increased (ú15 mm Hg) AaDo 2 . The mean values to be the favored mechanism for intrapulmonary vascular of exhaled NO output and serum NO 0 2 /NO 0 3 were significantly dilatations in cirrhosis, and nitric oxide (NO) has recently higher in cirrhotic patients than in controls (252 { 117 vs.ascended to the top of the list of possible substances. 6,7 75.2 { 19 nL/min/m 2 , P õ .0001; and 47.5 { 29.4 vs. 32.9NO is a powerful local vasodilator of endothelial origin, { 10.1 mmol/L, P õ .02, respectively). In all patients, there which contributes to the normally low pulmonary vascular was a significant correlation between exhaled NO and AaDo 2 tone. 8 NO has been shown to play an important role in regulat-(r Å .78, P õ .0001). Twelve patients (26.6%) were found to ing the vasomotor tone in experimental cirrhosis. 9,10 It is now have CE-echocardiographic evidence of intrapulmonary possible to measure NO produced in the lung by measuring its shunting (positive CE-echo). Nine patients were considered concentration in exhaled air. 11,12 Recently, increased NO output to have hepatopulmonary syndrome (HPS) on the basis of an in exhaled air has been reported in patients with advanced AaDo 2 ú 15 mm Hg and positive CE-echo. These 9 patients cirrhosis, in whom exhaled NO was associated with systemic had a mean value of exhaled NO significantly higher than circulatory disturbances. 13 Exhaled NO was reported to be patients without HPS (331 { 73.2 vs. 223 { 118.4 nL/min/ raised almost threefold in t...

ObjectiveTo estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer—CRC—or advanced adenoma).DesignProspective cohort of subjects aged 50–69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy.MethodsAll programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method.ResultsThe cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels.ConclusionThe association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

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Static and dynamic lung volumes, flow-volume curve in air and after He-O₂ were carried out in 5 normal subjects baseline, immediately after rapid infusion of 2 litres of normal saline, and then 15, 30 and 60 min after. At the end of the infusion, a marked reduction of ΔMEF₅₀, FVC, FEV₁, MEF₅₀, MEF₂₅ and an increase of Viso V and CV/VC were observed in all the subjects. The poor response to He-O₂ suggests a predominant increase of small airway resistance after rapid infusion. In the recovery phase, He-O₂ tests promptly returned to control values, while an increased CV/VC was detectable until 30 min after the infusion.