Endogenous Cushing's syndrome and cancer risk.

OBJECTIVE: Cancer incidence in patients with endogenous Cushing's syndrome (CS) has never been established. Here, we aimed to assess the cancer risk in patients with CS as compared with individually matched controls. DESIGN: A nationwide retrospective matched cohort study of patients with endogenous CS diagnosed between 2000 and 2023 using the database of Clalit Health Services in Israel. METHODS: Patients with adrenal carcinoma or ectopic CS were excluded. Patients with CS were matched in a 1:5 ratio, with controls individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was defined as the first diagnosis of any malignancy following a CS diagnosis. Risk of malignancy was calculated using the Cox proportional hazard model, with death as a competing event. RESULTS: A total of 609 patients with CS and 3018 controls were included [mean age at diagnosis, 48.0 ± 17.2 years; 2371 (65.4%) women]. The median follow-up was 14.7 years (IQR, 9.9-20.2 years). Patients with CS had an increased cancer risk, with a hazard ratio (HR) of 1.78 (95% CI 1.44-2.20) compared with their matched controls. The risk of malignancy was elevated in patients with Cushing's disease (251 cases and 1246 controls; HR 1.65, 95% CI 1.15-2.36) and in patients with adrenal CS (200 cases and 991 controls; HR 2.36, 95% CI 1.70-3.29). The increased cancer risk in patients with CS persists after exclusion of thyroid malignancies. CONCLUSION: Endogenous CS is associated with increased malignancy risk. These findings underscore the need for further research to establish recommendations for cancer screening in this population.

The Association Between Hypothyroidism Treatment and Mortality in Patients Hospitalized in Surgical Wards.

Limited data are available regarding the association between pre-admission thyroid-stimulating hormone (TSH) levels and prognosis in hospitalized surgical patients treated for hypothyroidism. We retrospectively evaluated a cohort of 1,451 levothyroxine-treated patients, hospitalized to general surgery wards. The 30-day mortality risk was 2-fold higher for patients with TSH of 5.0-10.0 mIU/L (adjusted OR, 2.3; 95% CI 1.1-5.1), and 3-fold higher for those with TSH > 10.0 mIU/L (3.4; 95% CI 1.3-8.7). Long-term mortality risk was higher in patients with TSH of 5.0-10.0 and above 10.0 mIU/L (adjusted HR, 1.2; 95% CI, 1.0-1.6, and 1.7; 95% CI 1.2-2.4, respectively). We found that in levothyroxine-treated adults hospitalized to surgical wards, increased pre-admission TSH levels are associated with increased short- and long-term mortality.

The Association between Multi-Vessel Coronary Artery Disease and High On-Aspirin Platelet Reactivity.

BACKGROUND: Multi-vessel coronary artery disease (MV-CAD) is correlated with worse clinical outcomes compared with single-vessel CAD (SV-CAD). The aim of this study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin. METHODS: The current study is an analysis of prospectively enrolled randomly selected patients with known stable CAD, who were taking aspirin (75-100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the enrollment to the study. EXCLUSION CRITERIA: acute coronary syndrome at the time of platelet function testing, active malignancy, acute infection, active inflammatory/rheumatic disease, major surgery in the past 6 months, chronic liver failure, treatment with oral anticoagulation, non-adherence with Aspirin and thrombocytopenia (<100 K/micl). Blood was drawn from the participants and sent for platelet function testing (VerifyNow, Instrumentation Laboratory Company, Bedford, Massachusetts, United States). MV-CAD was defined as >50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU) >550. RESULTS: Overall, 507 patients were analyzed; age 66.7 ± 11.2, 17.9% women, 223 (44%) had MV-CAD. The rate of HAPR was significantly higher among patients with MV-CAD vs. SV-CAD (14.8% vs. 3.5%, p < 0.001, respectively). Furthermore, a "dose response"-like association was found between the number of stenotic coronary arteries and the rate of HAPR (3.5%, 13.5 and 17.3% for SV-CAD, 2-vessel and 3-vessel disease, respectively). In a multivariate analysis adjusted for potential confounders, MV-CAD was found to be a strong independent predictor of HAPR [OR = 1.8 (95%CI: 1.05-4.7), p = 0.014]. CONCLUSIONS: A significant association between MV-CAD and HAPR was found. Additional studies designed to investigate the mechanisms of HAPR and different therapeutic options for this subset of patients are warranted.

Relation of Hypoalbuminemia to Response to Aspirin in Patients With Stable Coronary Artery Disease.

Serum albumin (SA) level is a powerful cardiovascular prognostic marker, suggested to be involved in regulation of platelet function. High on-aspirin platelet reactivity (HAPR) is associated with increased risk for deleterious cardiovascular events. The aim of the present study was to evaluate the association between HAPR and albumin levels in patients with stable coronary artery disease (CAD) treated with aspirin. Patients with known stable CAD, who were taking aspirin (75 to 100 mg qd) regularly for at least 1 month, were screened for the present study. Exclusion criteria: cancer, sepsis or acute infection, active inflammatory/rheumatic disease, recent major surgery, chronic liver failure, the administration of other antiplatelet drugs, nonadherence with aspirin and thrombocytopenia. Blood was drawn from the participants and sent for SA level and platelet function test (VerifyNow). HAPR was defined as aspirin reaction units (ARU) >550. Overall 116 patients were analyzed; age 69 ± 10, 28% women. Twenty (17%) were hypoalbuminemic (≤3.5 g/dl). Hypoalbuminemic patients had similar characteristics to the normal albumin group except mildly higher creatinine in the former. SA levels were significantly lower in the hypoalbuminemic group (3.2 ± 0.2 g/dl vs 4.2 ± 0.4 g/dl, respectively, p <0.001) whereas mean ARU was significantly higher compared with the normal albumin group (548 ± 45 vs 444 ± 66 ARU, respectively, p <0.001). A significant inverse association was observed between SA and ARU with (R2 = 0.67, p <0.001). Multivariate analysis adjusted for potential confounders found that albumin ≤3.5 is the strongest predictor of HAPR in patients with stable CAD (hazards ratio 4.9, 95% confidence interval 2.2 to 32, p = 0.002). In conclusion, hypoalbuminemia is strongly associated with HAPR in patients with stable CAD.

Effects of prasugrel pretreatment on angiographic myocardial perfusion parameters in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

OBJECTIVE: Prasugrel is a third-generation thienopyridine, with significant pharmacodynamic and clinical advantages over clopidogrel. There are few data on the effects of prasugrel therapy, as compared with clopidogrel, in terms of perfusion during percutaneous coronary intervention (PCI), in patients with ST-elevation myocardial infarction (STEMI). METHODS: A total of 128 patients with STEMI, pretreated with prasugrel 60 mg loading dose (mean age=55.9±9.1; 10.9% were women and 18.0% had diabetes), were compared with 128 propensity-matched patients pretreated with clopidogrel 600 mg (mean age=58.7±10.7; 10.2% were women and 19.5% had diabetes) for the primary endpoint of thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade at completion of the PCI. Secondary endpoints included the combined sum of major adverse events: death, reinfarction or target vessel revascularization at 1 year. RESULTS: Mean TIMI flow grade pre-PCI was similar between the two groups (1.31±1.3 in the prasugrel group and 1.30±1.2 in the clopidogrel group, P=0.96). However, after intervention, it was higher in the prasugrel group (2.94±0.24 vs. 2.84±0.37, respectively, P=0.016), as was myocardial blush (2.70±0.76 vs. 2.31±0.52, respectively, P<0.001). The percentage of TIMI 3 after intervention was also higher in the prasugrel group (97.70 vs. 90.60%, P=0.02). The combined rate of major adverse events at 1 year (8.7 vs. 11.6%, P=0.11), as well as total mortality (3.1±5.6 vs. 4.7±9.1%, P=0.52), did not differ between the two groups. CONCLUSION: In patients with STEMI undergoing primary PCI, pretreatment with prasugrel resulted in better angiographic perfusion results, as compared with pretreatment with clopidogrel.