Pyelonephritis in persons after age 50 as a clinical marker of urogenital cancer.

OBJECTIVES: Urinary tract infections have been linked with urinary tract cancer, but the association remains controversial. We examined whether pyelonephritis is a clinical marker of urogenital cancer. METHODS: We used Danish medical databases to create a population-based cohort of patients with an incident hospital-based pyelonephritis diagnosis during 1994-2013. Follow-up for cancer began at pyelonephritis diagnosis and ended on 30 November 2013. We restricted the cohort to patients older than 50 years, as urogenital cancer risk in the younger population is low. We calculated the absolute risk of urogenital cancer and the standardized incidence ratio (SIR) comparing risk observed in pyelonephritis patients to risk expected in the general population of Denmark. RESULTS: Among 15 070 patients with pyelonephritis, we observed 197 urinary tract cancers and 374 genital organ cancers over a 20-year follow-up period. The absolute risk of urogenital cancer was 1.5% 6 months after a pyelonephritis diagnosis, and the cumulative risk was 3.0% at 5 years. During the first 6 months following a pyelonephritis diagnosis, the SIR of urogenital cancer was 8.56 (95% CI 7.49-9.75). Between 6 and 12 months following this diagnosis, the SIR was 1.75 (95% CI 1.26-2.35), and beyond 1 year the SIR was approximately unity for most cancers. Notably, the SIR for bladder cancer among women remained elevated beyond 1 year of follow-up. CONCLUSIONS: Patients presenting with a hospital-based diagnosis of pyelonephritis had a higher 6-month risk of urogenital cancer than expected. However, causation cannot be inferred because of the study design.

Pneumonia and the incidence of cancer: a Danish nationwide cohort study.

OBJECTIVES: To examine the risk of a subsequent pulmonary or extra-pulmonary cancer diagnosis following a first-time hospital-based diagnosis of pneumonia. DESIGN: Population-based cohort study using Danish medical registries. SETTING: All hospitals in Denmark. SUBJECTS: A total of 342,609 patients with a first-time hospital-based (inpatient, emergency room or outpatient clinic) diagnosis of pneumonia between 1995 and 2011. MAIN OUTCOME MEASURES: We quantified the excess risk of various cancers amongst pneumonia patients compared to the expected risk in the general population, using relative [standardised incidence ratios (SIRs)] and absolute risk calculations. Follow-up started 1 month after a hospital-based diagnosis of pneumonia and ended on 31 December 2011. RESULTS: A total of 28,496 cancers were observed, compared with 21,625 expected, amongst 342,609 pneumonia patients followed for a median of 4.2 years. The absolute risk of a cancer diagnosis 1 to <6 months following a pneumonia diagnosis was 1.4%, with a corresponding SIR of 2.48 [95% confidence interval (CI) 2.41-2.55]. This was mainly due to an increased risk of lung cancer (eightfold) and haematological cancers (fourfold). The SIR for any cancer remained increased at 1.35 (95% CI 1.30-1.40) during 6-12 months of follow-up, and 1.20 (95% CI 1.18-1.22) during 1-5 years of follow-up. Beyond 5 years, an increased risk was maintained for lung, oesophageal, liver and bladder cancers, squamous cell carcinoma of the skin, lymphoma and multiple myeloma. CONCLUSIONS: A hospital-based pneumonia diagnosis was associated with an increased risk of a cancer diagnosis, especially in the ensuing months, but the absolute risk was small.

Hypercoagulability in cirrhosis: causes and consequences.

Decreased levels of most coagulation factors and thrombocytopenia are the main haemostatic abnormalities of cirrhosis. As a consequence, this condition was, until recently, considered as the prototype acquired coagulopathy responsible for bleeding. However, recent evidence suggests that it should, rather, be regarded as a condition associated with normal or even increased thrombin generation. The bleeding events that occur in these patients should, therefore, be explained by the superimposed conditions that frequently occur in this setting. Due to elevated levels of factor VIII (procoagulant driver) in combination with decreased protein C (anticoagulant driver), which are typically found in patients with cirrhosis, a procoagulant imbalance, defined as a partial resistance to the in vitro anticoagulant action of thrombomodulin, can be demonstrated. Whether this in vitro hypercoagulability is truly representative of what occurs in vivo remains to be established. However, the hypothesis that it may have clinical consequences is attractive and deserves attention. The possible consequences that we discuss herein include whether (i) cirrhosis is a condition associated with increased risk of venous thromboembolism or portal vein thrombosis; (ii) the hypercoagulability associated with cirrhosis has any other role outside coagulation (i.e. progression of liver fibrosis); and (iii) anticoagulation should be used in cirrhosis. Although apparently provocative, considering anticoagulation as a therapeutic option in patients with cirrhosis is now supported by a rationale of increasing strength. There may be subgroups of patients who benefit from anticoagulation to treat or prevent thrombosis and to slow hepatic fibrosis. Clinical studies are warranted to explore these therapeutic options.

Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case-control study.

BACKGROUND: Atherosclerotic disease has been associated with the risk of venous thromboembolism, but the available data are conflicting. There are similar confusions regarding the association of the use of aspirin and statins with venous thromboembolism. OBJECTIVES: To determine whether arterial cardiovascular events, use of statins and low-dose aspirin were associated with the risk of venous thromboembolism. PATIENTS AND METHODS: In this population-based case-control study, we identified 5824 patients with venous thromboembolism and 58 240 population controls with a complete hospital and prescription history. We used logistic regression to estimate the relative risk of venous thromboembolism, adjusted for potentially confounding factors. RESULTS: Patients with a history of arterial cardiovascular events had a clearly increased relative risk. An event within 3 months before the index date conferred large increases in risk [relative risk 4.22 (95% confidence interval (CI), 2.33-7.64) after myocardial infarction, 4.41 (95% CI, 2.92-6.65) after stroke]. Myocardial infarction more than 3 months before the index date was not significantly associated with risk, although there was a relative risk of 1.29 (95% CI, 1.05-1.57) for myocardial infarction more than 60 months previously. A history of stroke was associated with small increases in risk after 3 months. Current use of statins was associated with a reduced risk of venous thromboembolism [relative risk=0.74 (95% CI, 0.63-0.85)]. Aspirin use was not associated with risk. CONCLUSIONS: Patients with cardiovascular events are at a short-term increased risk of venous thromboembolism. Statins might prevent venous thromboembolism but aspirin does not. However, as the study is non-randomized residual confounding cannot be excluded.