A biomarker for bacteremia in pregnant women with acute pyelonephritis: soluble suppressor of tumorigenicity 2 or sST2.

Objective: Sepsis is a leading cause of maternal death, and its diagnosis during the golden hour is critical to improve survival. Acute pyelonephritis in pregnancy is a risk factor for obstetrical and medical complications, and it is a major cause of sepsis, as bacteremia complicates 15-20% of pyelonephritis episodes in pregnancy. The diagnosis of bacteremia currently relies on blood cultures, whereas a rapid test could allow timely management and improved outcomes. Soluble suppression of tumorigenicity 2 (sST2) was previously proposed as a biomarker for sepsis in non-pregnant adults and children. This study was designed to determine whether maternal plasma concentrations of sST2 in pregnant patients with pyelonephritis can help to identify those at risk for bacteremia.Study design: This cross-sectional study included women with normal pregnancy (n = 131) and pregnant women with acute pyelonephritis (n = 36). Acute pyelonephritis was diagnosed based on a combination of clinical findings and a positive urine culture. Patients were further classified according to the results of blood cultures into those with and without bacteremia. Plasma concentrations of sST2 were determined by a sensitive immunoassay. Non-parametric statistics were used for analysis.Results: The maternal plasma sST2 concentration increased with gestational age in normal pregnancies. Pregnant patients with acute pyelonephritis had a higher median (interquartile range) plasma sST2 concentration than those with a normal pregnancy [85 (47-239) ng/mL vs. 31 (14-52) ng/mL, p < .001]. Among patients with pyelonephritis, those with a positive blood culture had a median plasma concentration of sST2 higher than that of patients with a negative blood culture [258 (IQR: 75-305) ng/mL vs. 83 (IQR: 46-153) ng/mL; p = .03]. An elevated plasma concentration of sST2 ≥ 215 ng/mL had a sensitivity of 73% and a specificity of 95% (area under the receiver operating characteristic curve, 0.74; p = .003) with a positive likelihood ratio of 13.8 and a negative likelihood ratio of 0.3 for the identification of patients who had a positive blood culture.Conclusion: sST2 is a candidate biomarker to identify bacteremia in pregnant women with pyelonephritis. Rapid identification of these patients may optimize patient care.

Evaluation of the optimal sequence of adjuvant chemotherapy and radiation therapy in the treatment of advanced endometrial cancer.

OBJECTIVE: The optimal sequence of adjuvant chemoradiation in the treatment of advanced endometrial carcinoma (EC) remains unclear. We sought to evaluate the outcomes of patients treated with chemoradiation in sandwich fashion (chemotherapy-radiotherapy-chemotherapy; CRC), versus those treated sequentially (chemotherapy-radiotherapy; CR) (radiotherapy-chemotherapy; RC), to determine if there is a survival advantaged associated with a particular treatment sequence. METHODS: A multicenter retrospective analysis of patients with stage III and IV EC from 2000-2018 was conducted. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemoradiation. Differences in the frequencies of adverse events were evaluated using Pearson's χ² test. Progression free survival (PFS) and overall survival (OS) rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 152 patients; 36.8% (n=56) CRC, 28.9% (n=44) CR, and 34.2% (n=52) RC. Histology included 44.0% endometrioid, 47.5% serous and 8.5% clear cell tumors. There was no difference in the frequency of histology (p=0.973), stage (p=0.143), cytoreduction status (p=0.932), or treatment delays (p=0.571) between adjuvant therapy sequences. The most frequent location of disease recurrence was abdomen. The median PFS favored CRC versus CR or RC (36-months vs. 22-months and 24-months, respectively) (p=0.038), as did the median OS (48-months vs. 28-months and 34-months, respectively) (p=0.003). CRC demonstrated superiority over CR and RC sequencing in terms 3-year PFS (55% vs. 34% and 37%, respectively) and 3-year OS (71% vs. 50% and 52%, respectively). CONCLUSIONS: Adjuvant chemoradiation delivered in CRC sequence was associated with improvements in both PFS and OS compared to alternant therapy sequencing.

A clinicopathologic study of endometrial cancer metastatic to bone: Identification of microsatellite instability improves treatment strategies.

Metastasis to bone (BM) is an uncommon manifestation of advanced endometrial cancer (EC). The present study will review the clinicopathologic features of a cohort of patients with EC and BM. We conducted a multi-center retrospective review of patients with EC and BM. Demographic and clinical information was extracted from the medical records. Survival outcomes were determined using Kaplan-Meier Curves. Final analysis included 10 patients. The median age was 65 years (range 31-71). 80% had FIGO stage III/IV disease. The most common site of BM was the spine (66%). All patients presented with extraosseous dissemination at the time of diagnosis of BM and 70% were found to have multiple sites of BM. 80% of patients were diagnosed with BM in the recurrent setting. The median time to diagnosis of bone recurrence was 14 months (range: 0-44). Median survival after diagnosis of BM was 11 months (range: 1-22 months). Patients with endometrioid histology and single site of bone metastasis experienced improved survival (p = 0.04 and p = 0.05, respectively). Eight patients had immunohistochemistry or molecular tumor profiles available for review. Seven of these patients (87.5%) were found to have microsatellite instability (MSI). The most common mutation was hypermethylation of MLH-1 (43%). To our knowledge, this is the first report demonstrating a correlation between MSI and metastasis to bone. The identification of BM in EC is uncommon, but will alter treatment strategies and dramatically impact prognosis. Molecular tumor profiling should be performed to identify targeted therapy options and optimize adjuvant treatment strategies.