Monitoring levels of circulating cell-free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment.

Circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib-treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression-free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and, partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline cfDNA > 26 ng·mL-1 had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; log-rank P = 0.0366). Patients with baseline mutant ctDNA > 2 ng·mL-1 had shorter OS than those with mutant ctDNA below this threshold (log-rank P = 0.0154). We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment.

Hepatitis C Virus Infection Among Women Giving Birth - Tennessee and United States, 2009-2014.

Hepatitis C virus (HCV) affects an estimated 3.5 million persons in the United States (1), making it the most common bloodborne infection in the country. Recent surveillance data showed increased rates of HCV infection among adolescents and adults who are predominantly white, live in nonurban areas, and have a history of injection drug use.* U.S. birth certificate data were used to analyze trends and geographic variations in rates of HCV infection among women giving birth during 2009-2014. Birth certificates from Tennessee were used to examine individual characteristics and outcomes associated with HCV infection, using a multivariable model to calculate adjusted odds of HCV-related diagnosis in pregnancy among women with live births. During 2009-2014, HCV infection present at the time of delivery among pregnant women from states reporting HCV on the birth certificate increased 89%, from 1.8 to 3.4 per 1,000 live births. The highest infection rate in 2014 (22.6 per 1,000 live births) was in West Virginia; the rate in Tennessee was 10.1. In adjusted analyses of Tennessee births, the odds of HCV infection were approximately threefold higher among women residing in rural counties than among those in large urban counties, 4.5-fold higher among women who smoked cigarettes during pregnancy, and nearly 17-fold higher among women with concurrent hepatitis B virus (HBV) infection. HCV infection among pregnant women is an increasing and potentially modifiable threat to maternal and child health. Clinicians and public health officials should consider individual and population-level opportunities for prevention and risk mitigation.

Implementation of a statewide surveillance system for neonatal abstinence syndrome - Tennessee, 2013.

Over the last decade, rates of opioid pain reliever prescribing grew substantially in the United States, affecting many segments of the population, including pregnant women. Nationally, Tennessee ranks second in the rate of prescriptions written for opioid pain relievers, with 1.4 per person in 2012. The rising prevalence of opioid pain reliever use and misuse in Tennessee led to an increase in adverse outcomes in the state, including neonatal abstinence syndrome (NAS). NAS is a withdrawal syndrome experienced by infants shortly after birth. The syndrome most commonly occurs after antenatal exposure to opioids, although other medications have also been implicated. From 2000 to 2009, the incidence rate of NAS in Tennessee increased from 0.7 to 5.1 per 1,000 births, exceeding the national average, which increased from 1.2 to 3.4 per 1,000 births. NAS is associated with numerous morbidities for the infant, including low birth weight, poor feeding, and respiratory problems. Previous population-based analyses of NAS relied on hospital discharge data, which typically become available for analysis only after substantial delay. In Tennessee, the rising incidence of NAS and its associated public health burden created an urgent need for timelier incidence figures to drive policy and prevention efforts. Beginning January 1, 2013, the Tennessee Department of Health (TDH) made NAS reporting mandatory. A total of 921 cases were reported in 2013 (among 79,954 births), with the most cases clustered in eastern Tennessee; 63% of cases occurred to mothers who were reported to be using at least one substance prescribed by a health care provider (e.g., opioid pain relievers or maintenance medications for opioid dependency), and 33% of cases occurred among women using illicit or diverted substances (e.g., heroin or medications prescribed for someone else). The first year's surveillance results highlight the need for primary prevention activities focused on reducing dependence/addiction among women of childbearing age and preventing unintended pregnancy among female opioid users.

Clinical characteristics of human monkeypox, and risk factors for severe disease.

BACKGROUND: Human monkeypox is an emerging smallpox-like illness that was identified for the first time in the United States during an outbreak in 2003. Knowledge of the clinical manifestations of monkeypox in adults is limited, and clinical laboratory findings have been unknown. METHODS: Demographic information; medical history; smallpox vaccination status; signs, symptoms, and duration of illness, and laboratory results (hematologic and serum chemistry findings) were extracted from medical records of patients with a confirmed case of monkeypox in the United States. Two-way comparisons were conducted between pediatric and adult patients and between patients with and patients without previous smallpox vaccination. Bivariate and multivariate analyses of risk factors for severe disease (fever [temperature, > or =38.3 degrees C] and the presence of rash [> or =100 lesions]), activity and duration of hospitalization, and abnormal clinical laboratory findings were performed. RESULTS: Of 34 patients with a confirmed case of monkeypox, 5 (15%) were defined as severely ill, and 9 (26%) were hospitalized for >48 h; no patients died. Previous smallpox vaccination was not associated with disease severity or hospitalization. Pediatric patients (age, < or =18 years) were more likely to be hospitalized in an intensive care unit. Nausea and/or vomiting and mouth sores were independently associated with a hospitalization duration of >48 h and with having > or =3 laboratory tests with abnormal results. CONCLUSION: Monkeypox can cause a severe clinical illness, with systemic signs and symptoms and abnormal clinical laboratory findings. In the appropriate epidemiologic context, monkeypox should be included in the differential diagnosis for patients with unusual vesiculopustular exanthems, mucosal lesions, gastrointestinal symptoms, and abnormal hematologic or hepatic laboratory findings. Clinicians evaluating a rash illness consistent with possible orthopoxvirus infection should alert public health officials and consider further evaluation.