Procalcitonin kinetics in pediatric patients with systemic inflammatory response after open heart surgery

Objective To evaluate procalcitonin and C-reactive protein as markers of inflammation severity and their value in predicting development of organ failure after pediatric open heart surgery.Design Prospective, observational, clinical study.Setting Single university hospital.Patients Thirty-three pediatric patients with systemic inflammatory response syndrome (SIRS; n = 19) and SIRS+organ failure (SIRS+OF; n = 14) following open heart surgery were included.Measurements and results Plasma procalcitonin and C-reactive protein levels were measured before and after the operation, and 1, 2, 3, and 4 days after surgery. Patients were evaluated daily to assess organ failure. Postoperative procalcitonin levels in the SIRS+OF group were significantly higher than in the SIRS group. C-reactive protein levels were similar between the groups throughout the study period. Peak procalcitonin levels were found to be positively correlated with aortic cross-clamp and cardiopulmonary bypass times, duration of mechanical ventilation, intensive care unit and hospital stay, mortality and organ failure development. Peak procalcitonin was found to be a good predictor of postoperative organ failure development and mortality. However, the predictive value of peak C-reactive protein for organ failure and mortality was found to be weak. Double-peak procalcitonin curves were observed in SIRS+OF patients with infection during the intensive care unit stay.Conclusion In the SIRS+OF group peak procalcitonin levels were found to be highly predictive for mortality and organ failure development, whereas C-reactive protein levels were not. Daily procalcitonin measurements in SIRS+OF patients may help identify the postoperative infection during the follow-up period.     

Reference interval of pregnancy-associated plasma protein-A in healthy men and non-pregnant women

ObjectiveThe serum pregnancy-associated plasma protein-A (PAPP-A) concentration is a predictor of ischemic cardiac events and renal impairment. However, the reference interval of PAPP-A has not been determined. This study determined the reference interval of PAPP-A in men and non-pregnant women.MethodsThe study enrolled 126 apparently healthy individuals (52 males and 74 females). The mean age of the men and women was 34.7 (range 20–66) years and 34.6 (range 18–65) years, respectively. Serum PAPP-A concentrations were determined using an ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated using the bootstrap method.ResultsThe results for three subjects were outliers, so the reference interval of PAPP-A was calculated using the data for 123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of PAPP-A for men and women (with the 90% confidence interval) was <22.9 ng/mL (19.7–23.3) and <33.6 ng/mL (25.2–36.7), respectively. In male subjects, serum PAPP-A levels of smokers [3.10 (UD, 7.30) ng/mL] were significantly lower than that of non-smokers [11.00 (UD, 24.4) ng/mL] (p < 0.001) and there was a positive correlation between serum PAPP-A levels and subjects’ age (r = 0.439; p < 0.001).ConclusionsThe reference interval of PAPP-A differed for men and non-pregnant women. In clinical practice, <22.9 ng/mL for men and <33.6 ng/mL for non-pregnant women may be used as reference intervals for PAPP-A.     

Predictive cutoff point of admission N-terminal pro–B-type natriuretic peptide testing in the ED for prognosis of patients with acute heart failure

Objective

The main objective of this study was to determine a cutoff level of plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP) that could successfully predict the short- and long-term prognosis of patients with acute heart failure at the time of admission to the emergency department. The results of our study are presented in context with previously published literature. We believe that the present study will be useful and salutary for the progress of literature.

Methods

N-terminal pro–B-type natriuretic peptide plasma levels were obtained from 100 patients with shortness of breath and left ventricular dysfunction upon admission to the emergency department. All patients underwent follow-up evaluations 30 days and 1 year after admission. The end point was defined as all-cause mortality.

Results

The mean age of the patients in this study was 70.8 ± 11.6 years, and 51% were female. All-cause mortality at the 30-day and 1-year follow-up evaluations was 21.2% and 53.5%, respectively. We determined that the optimal NT-proBNP cutoff point for predicting 30-day mortality at the time of admission was 9152.4 pg/mL, with a 71.4% sensitivity and an 81.3% specificity (95% confidence interval, area under the curve: 0.726; P = .002). The optimal NT-proBNP cutoff point for predicting 1-year mortality at the time of admission was 3630.5 pg/mL, with an 83.0% sensitivity and a 52.2% specificity (95% confidence interval, area under the curve: 0.644; P = .014).

Conclusion

Elevated NT-proBNP levels at the time of admission are a strong and independent predictor of all-cause mortality in patients with acute heart failure at 30 days and 1 year after admission. Furthermore, the optimal cutoff level of NT-proBNP used to predict 30-day and 1-year mortality had high sensitivity.     

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.