Role of demographics in non-invasive testing for colorectal cancer screening: do targeted cut-off values improve detection?

BACKGROUND: Fecal immunochemical test (FIT) is a yearly alternative colorectal screening modality for average risk individuals unwilling or unable to undergo invasive colorectal cancer (CRC) screening due to cost and accessibility. This study aims to determine whether FIT should be interpreted within the context of patient demographics and medical history. METHODS: Patients >50 years old who had a FIT followed by colonoscopy within 1 year were analyzed based on age, race, BMI, social and medical comorbidities. False positive (FP) and false negative (FN) FIT results within each patient demographic and medical history variable were determined by comparing with the gold standard of colonoscopy using Chi-square analysis. RESULTS: 1025 patients were reviewed. 21.8% of FIT results were positive. Factors which differed in positive FIT rates were age (p=0.003), smoking (p<0.001), alcohol (p=0.001), and hypertension (p<0.001). The difference in rates of FP and FN FIT outcomes among each variable underwent further sub-analysis. The FP was 66.8% and the FN rate was 12.8%. Higher FN outcomes were noted in those above 70, males and smokers, though the result was only statistically significant for males (p=0.009). Females were observed to have higher FP rates (p=0.019). CONCLUSIONS: Females had higher FP FIT rates compared to males, indicating that sex may influence FIT outcomes and should be accounted for when interpreting FIT results. This information can be utilized to identify populations at higher risk of FP or FN FIT results to target CRC screening. Additionally, recalculating the FP and FN rates for each variable may help determine new FIT targets.

Dynamic Changes in the Molecular Signature of Adverse Left Ventricular Remodeling in Patients With Compensated and Decompensated Chronic Primary Mitral Regurgitation.

BACKGROUND: There is no proven medical therapy that attenuates adverse left ventricular remodeling in patients with chronic primary mitral regurgitation (CPMR). Identification of molecular pathways important in the progression of left ventricular remodeling in patients with CPMR may lead to development of new therapeutic strategies. METHODS AND RESULTS: We performed baseline echocardiographic, cardiac catheterization, and serum NT-pro-BNP analysis in patients with severe CPMR awaiting mitral valve surgery and stratified the study population into compensated or decompensated CPMR. We obtained left ventricular endomyocardial biopsies (n=12) for mRNA expression analysis, and compared baseline transcript levels of 109 genes important in volume-overload left ventricular remodeling with levels in normal hearts (n=5) and between patients with compensated (n=6) versus decompensated (n=6) CPMR. Patients were then randomized to treatment with and without carvedilol and followed until the time of surgery (mean follow-up 8.3 months) when repeat endomyocardial biopsies were obtained to correlate transcriptional dynamics with indices of adverse remodeling. CPMR was associated with increased NPPA expression levels (21.6-fold, P=0.004), decreased transcripts of genes important in cell survival, and enrichment of extracellular matrix genes. Decompensated CPMR was associated with downregulation of SERCA2 (0.77-fold, P=0.009) and mitochondrial gene expression levels and upregulation of genes related to inflammation, the extracellular matrix, and apoptosis, which were refractory to carvedilol therapy. CONCLUSIONS: Transition to decompensated CPMR is associated with calcium dysregulation, increased expression of inflammatory, extracellular matrix and apoptotic genes, and downregulation of genes important in bioenergetics. These changes are not attenuated by carvedilol therapy and highlight the need for development of specific combinatorial therapies, targeting myocardial inflammation and apoptosis, together with urgent surgical or percutaneous valve interventions.

A 10 years audit of cardiothoracic referrals from a pulmonology service in a developing country: impact of patient human immunodeficiency virus status.

BACKGROUND: There are few studies that have documented the clinical presentation, complication rate and outcome of cardiothoracic referrals from a Pulmonology Service, particularly in developing countries. Furthermore, the impact of human immunodeficiency virus (HIV) status on such referrals and their outcomes is not well documented. METHODS: This was a retrospective audit of combined pulmonologist/cardiothoracic consultations, undertaken among the tertiary academic hospitals attached to the University of the Witwatersrand, Johannesburg, South Africa, over a 10 years period (2001-2010) in order to document the clinical features of these referrals and to determine any impact of HIV status on trends in disease presentations, complications and outcome. RESULTS: A total of 847 patients were evaluated on whom a variety of surgical procedures was performed, 50.4% being therapeutic, 32.8% diagnostic and 16.9% both therapeutic and diagnostic. HIV status was known in 488 cases. Of these 229 (46.9%) were HIV-seropositive and 259 (53.1%) -seronegative. The main reasons for referral were for infective conditions, including tuberculosis (TB), pleural disease/effusion/empyema, and other bacterial infections, with significantly more of the TB patients being HIV-seropositive (P<0.0001).There was a trend for increasing presentations for TB and pleural conditions, particularly during the last 4-5 years of the audit, coinciding with an increase in the numbers of HIV-positive referrals. HIV status had no impact on the frequency of surgical complications or mortality. CONCLUSIONS: The audit indicates an increasing referral rate of HIV-seropositive patients to cardiothoracic services in Johannesburg, particularly in association with TB and pleural diseases. However with careful cardiothoracic/pulmonologist evaluation of the cases the frequency of complications and mortality appear to be no different from that of HIV-seronegative cases.

Descending mediastinitis.

We studied 13 patients with mediastinal abscesses caused by oropharyngeal infections, who presented between April 2007 and June 2011. All patients were operated on after maxillofacial and ear, nose and throat surgeons had treated the primary source and drained all collections in the neck. Thoracic surgery was performed in the same session. Anterior mediastinal collections were drained via a small mediastinotomy. Posterior collections were approached via a thoracotomy. Chest computed tomography was essential to delineate the extent of disease. A thoracotomy approach was used in 7 patients; 2 of them required an anterior mediastinotomy on the opposite side. The others had an anterior mediastinotomy which was bilateral in 2 cases. After repeat computed tomography, 5 patients were operated on for suspected new loculations; tissue edema had caused false imaging in 3 of them. There was no mortality. Early after eradication of the source and pathways to the mediastinum, gravity drainage of mediastinal abscesses, and good antibiotic cover, with repeat computed tomography after 3 days, was an effective approach in this highly fatal disease.