Community acquired pneumonia: risk factors associated with mortality in a tertiary care hospitalized patients

OBJECTIVE: To evaluate risk factors associated with mortality in patients hospitalized with CommunityAcquired Pneumonia (CAP) from a developing country. METHODS: An observational study was conducted on adult patients admitted with a diagnosis of CAP from January 2002 to August 2003 at Aga Khan University hospital, Karachi, Pakistan. Clinical records were reviewed for demographic characteristics, clinical and laboratory features, hospital course, and risk factors associated with mortality. RESULTS: A total of 329 patients (187 males) were admitted with CAP. Two-third of patients had underlying co-morbid medical illnesses. Complications developed in 15.7% cases and the overall mortality rate was 11%. Risk factors were identified on initial clinical assessment, laboratory and radiological features and during hospital course. On admission elevated blood urea, new onset of confusion, abnormal liver function test, low serum albumin, cardiomegaly and presence of underlying malignancy were strongly associated with increased mortality. Failure to respond to therapy was associated with a high risk of mortality as depicted by complication during hospital stay (Odds Ratio = 23.3, 95% Confidence Interval = 10.3-52.8), need for mechanical ventilation (OR = 17.1, 95% CI = 7.4-39.8) and need for intensive care unit (OR = 9, 95% CI = 4.2-19.3). CONCLUSIONS: Abnormal liver function test, low albumin and presence of cardiomegaly were more significant mortality risk factors than age, respiratory rate and blood pressure. Elevated blood urea and confusion remain strong risk factors on admission. Failure of response to therapy and onset of complications heralded a high risk of death

High-altitude pulmonary hypertension in cattle (brisket disease): Candidate genes and gene expression profiling of peripheral blood mononuclear cells

High-altitude pulmonary hypertension (HAPH) is a consequence of chronic alveolar hypoxia, leading to hypoxic vasoconstriction and remodeling of the pulmonary circulation. Brisket disease in cattle is a naturally occurring animal model of hypoxic pulmonary hypertension. Genetically susceptible cattle develop severe pulmonary hypertension and right heart failure at altitudes >7,000 ft. No information currently exists regarding the identity of the pathways and gene(s) responsible for HAPH or influencing severity. We hypothesized that initial insights into the pathogenesis of the disease could be discovered by a strategy of (1) sequencing of functional candidates revealed by single nucleotide polymorphism (SNP) analysis and (2) gene expression profiling of affected cattle compared with altitude-matched normal controls, with gene set enrichment analysis (GSEA) and Ingenuity pathway analysis (IPA). We isolated blood from a single herd of Black Angus cattle of both genders, aged 12-18 months, by jugular vein puncture. Mean pulmonary arterial pressures were 85.6±13 mmHg STD in the 10 affected and 35.3±1.2 mmHg STD in the 10 resistant cattle, P<0.001. From peripheral blood mononuclear cells, DNA was hybridized to an Affymetrix 10K Gene Chip SNP, and RNA was used to probe an Affymetrix Bovine genome array. SNP loci were remapped using the Btau 4.0 bovine genome assembly. mRNA data was analyzed by the Partek software package to identify sets of genes with an expression that was statistically different between the two groups. GSEA and IPA were conducted on the refined expression data to identify key cellular pathways and to generate networks and conduct functional analyses of the pathways and networks. Ten SNPs were identified by allelelic association and four candidate genes were sequenced in the cohort. Neither endothelial nitric oxide synthetase, NADH dehydrogenase, TG-interacting factor-2 nor BMPR2 were different among affected and resistant cattle. A 60-gene mRNA signature was identified that differentiated affected from unaffected cattle. Forty-six genes were overexpressed in the affected and 14 genes were downregulated in the affected cattle by at least 20%. GSEA and Ingenuity analysis identified respiratory diseases, inflammatory diseases and pathways as the top diseases and disorders (P<5.14×10-14), cell development and cell signaling as the top cellular functions (P<1.20×10-08), and IL6, TREM, PPAR, NFkB cell signaling (P<8.69×10-09) as the top canonical pathways associated with this gene signature. This study provides insights into differences in RNA expression in HAPH at a molecular level, and eliminates four functional gene candidates. Further studies are needed to validate and refine these preliminary findings and to determine the role of transcribed genes in the development of HAPH