Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis

IntroductionAcute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown.MethodsIn a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality.ResultsIn total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality.ConclusionAspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.     

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

The differential diagnosis between intrahepatic cholestatic jaundice and viral hepatitis during pregnancy.

Clinical and laboratory findings from 15 patients with icteric viral hepatitis during pregnancy (VHP) and from 22 patients with intrahepatic cholestasis during pregnancy (CJP) were evaluated statistically in order to find out which parameters might help in order to find out which parameters might help in differentiating the two diseases. Diagnosis was established by needle liver biopsy in all cases. The following data were considered: history, physical examination, erythrocyte sedimentation rate (ESR) serum cholesterol, prothrombin time, total serum bilirubin, SGOT, SGPT, serum alkaline phosphatase, serum protein, serum flocculation tests, BSP blood clearance and serum HB Ag. Vomiting, high GOT and GPT serum levels, and serum HB Ag positivity suggest VHP diagnosis. Otherwise a severe itching with scratching lesions, high ESR, elevated total cholesterol and serum alkaline phosphatase values mainly if occurring in the later stage of pregnancy are consistent with CJP diagnosis. When clinical and laboratory data from a jaundiced pregnant female do not allow diagnosis, this can be established only on the basis of needle liver biopsy.     

Negative charge distribution and density on the surface of oxygenated normal and sickle red cells

Negative charges on the external surface of red cells were visualized by colloidal iron hydroxide labelling of 50% of the membrane area after osmotic hemolysis and glutaraldehyde fixation. Counts were made over randomly selected areas on electron micrographs at 350,000 x magnification. Statistical analyses showed that at the 95% level of confidence there was no significant difference between oxygenated normal (AA) and sickle (SS) cells in either the distribution or the density of negative charges.     

Delta agent infection: an unfavourable event in HBsAg positive chronic hepatitis

To investigate the clinical value of delta agent infection in HBsAg positive chronic hepatitis, we detected anti-delta antibody (anti-delta) in serum and delta antigen (delta-Ag) on sequential liver biopsies of nine patients with HBsAg-positive CPH and 45 patients with HBsAg-positive CAH without cirrhosis observed for at least 2 years. The initial group of patients with CAH was composed of 54 patients who were consecutively either left untreated or treated with 15 mg of prednisolone daily. Nine patients dropped out. Delta-Ag was searched by the direct immunofluorescence technique. HBsAg, anti-delta, HBeAg and anti-HBe were detected by RIA. All CPH patients were delta-Ag negative in the 1st liver biopsy and anti-delta negative in serum. Out of these nine patients, seven remained delta-Ag negative CPH throughout the observation and the remaining two became delta-Ag positive, anti-delta positive and developed CAH. The 73% of patients with CAH were delta-Ag positive on the 1st biopsy and anti-delta positive in serum. The patients in the delta-Ag positive group (24 were always delta-Ag positive and two became delta-Ag positive during the observation) more frequently than those in the delta-Ag negative group (10 were always delta-Ag negative and nine became delta-Ag negative during the study) showed deterioration or died (77 vs. 16%; P less than 0.001). Neither in the delta-Ag positive group nor in the delta-Ag negative group did prednisolone modify the course of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of dipyridamole-induced ischemia by antianginal therapy in humans. Correlation with exercise electrocardiography.

BACKGROUND. Dipyridamole echocardiography test (DET: two-dimensional echocardiographic monitoring with dipyridamole infusion up to 0.84 mg/kg in 10 minutes) is a useful tool for the noninvasive diagnosis of coronary artery disease. Aims of the present study were to assess the effects of antianginal drugs on dipyridamole-induced ischemia and to evaluate whether drug-induced changes in DET response may predict variations in exercise tolerance. METHODS AND RESULTS. Fifty-seven patients with angiographically assessed significant coronary artery disease (greater than 70% lumen reduction in at least one major coronary vessel) performed a DET and an exercise electrocardiography test (EET) in random order both off treatment and on antianginal drugs (beta-blockers, calcium antagonists and nitrates, alone or in various combinations). The criterion for DET positivity was a transient dyssynergy of contraction absent or of a lesser degree in the baseline examination. In DET, two parameters were evaluated: the dipyridamole time (i.e., the time from onset of dipyridamole infusion to obvious dyssynergy) and the wall motion score index. DET sensitivity was 91% off therapy and fell to 65% under therapy (p less than 0.01). In the 37 patients who had a positive DET both off and on therapy, the dipyridamole time increased from 6 +/- 3 (off therapy) to 8 +/- 3 minutes (on therapy) (p less than 0.01). The wall motion score index at peak dipyridamole went from 1.38 +/- 0.14 to 1.31 +/- 0.14 (p less than 0.01). EET and DET yielded concordant (positive versus negative) results in 41 of 57 (71%) patients off and in 35 of 57 (61%) on therapy (p = NS). In the subgroup of 38 patients with both positive DET and EET without treatment, the therapy-induced variations in exercise time were significantly correlated with the variations in dipyridamole time (r = 0.5; p less than 0.01), not with variations in wall motion score index (r = 0.3; p = NS). CONCLUSIONS. 1) Antianginal therapy can protect from dipyridamole-induced ischemia and 2) the therapy-induced changes in DET response parallel variations in exercise tolerance and might be useful for the objective, exercise-independent assessment of the therapy efficacy.     

Intracardiac ectopic thyroid: a report of a clinical case with a long-term follow-up

We describe the prolonged follow-up of a 64-year-old female patient, with an ectopic intracardiac thyroid gland. The mass was first detected 14 years ago, during a routine echocardiographic examination. The patient suffered from episodes of palpitation and cardiac auscultation revealed a systolic murmur. At cardiac surgery a right ventricular mass penetrating most of the interventricular septum was found. The mass was also prolapsing into the pulmonary infundibulum and could not be removed. On histopathology examination, the presence of a normal tissue was demonstrated. Two main clinical events characterized the prolonged follow-up: the gradual development of a massive tricuspid insufficiency, probably due to the strict anatomic relationship between the septal tricuspid papillary muscle and the mass itself; frequent supraventricular arrhythmias, partially refractory to different pharmacologic regimens, which could be ascribed to the chronic overload of the right atrium. The mass size has been stable over the years, and no thyroid hormone derangement was ever found.     

Prolonged Treatment of Children with Chronic Hepatitis B with Recombinant α2a-Interferon: A Controlled, Randomized Study

A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease.