Pain characteristics and age-related pain trajectories in infants and young children with sickle cell disease.

BACKGROUND: The epidemiology of painful episodes in infants and younger children with SCD has not been well studied, particularly for pain managed at home. PROCEDURE: SCD infants identified by newborn screening were enrolled in a longitudinal observational study of pain symptoms requiring parents to report the presence or absence of pain daily. When sickle cell related-pain events occurred, pain occurrence, location, associated symptoms and the treatment provided also were reported. RESULTS: 103 children were enrolled at a median age of 7.2 months; 50 had an SS genotype, 32 SC, 6 SB(0)thalassemia, and 15 SB(+)thalassemia. Parents/guardians reported for a median of 3.8 years (range 0.3-7.6 years) assessing pain for a total of 141,197 days, excluding any period of recurrent transfusions, with an additional 28,079 days of missing data (16%). Children had pain reported on 2,288 days (1.6%), representing 768 distinct episodes of pain, of which 108 required hospitalizations (14%). Pain locations and symptoms consistent with dactylitis were most prevalent (80%) in the 0-12 month age group, and became progressively less prevalent thereafter. Group-based trajectory modeling of pain episode or pain day frequency identified several trajectory groups with progressively older ages of peak pain frequency, which included 40-45% of SS/SB(0)thalassemia and 10-12% of SC/SB(+)thalassemia children. CONCLUSIONS: Pain is relatively infrequent in SCD infants and young children and commonly managed at home. Analyses of longitudinal pain trajectories suggest several different pain trajectories, differing in their frequency, age of onset, and age at peak pain frequency with clinical implications for hydroxyurea management.

Differential expression of cytochrome P450 omega-hydroxylase isoforms and their association with clinicopathological features in pancreatic ductal adenocarcinoma.

BACKGROUND: The cytochrome P450 (CYP) superfamily consists of enzymes that catalyze the oxidation of lipids, steroids, and drugs. In particular, the CYP4 family plays an essential role in lipid metabolism by the ω-hydroxylation of terminal ends of fatty acids. Disturbance of this system has been associated with increased angiogenesis, proliferation, and metastasis of several cancers. This study aimed to detect the expression of CYP4 isoforms (CYP4A11, CYP4F2, CYP4F3) in pancreatic ductal adenocarcinoma (PDA) and their association with clinicopathological features. METHODS: Pancreatic specimens were collected from 73 patients who underwent surgical resection at the Thomas Jefferson University Hospital. Quantitative polymerase chain reaction was used to examine the cytochrome P450 isoforms in PDA (n = 62), adjacent-normal (n = 30), and benign tissues (n = 11). Logistic regression models were used to analyze gene expression among tissue types. Spearman rank correlations were calculated for isoform expression and for age. Differences in expression by gender were assessed via t test. Other clinicopathological variables (diabetes, smoking, obesity, T stage, perineural invasion, nodal status) were analyzed by Wilcoxon rank sum. RESULTS: CYP4 expression for isoforms was significantly higher in PDA tissues versus matched-adjacent tissues (p < 0.01). PDA tumors expressed significantly higher levels of CYP4F2 and CYP4F3 when compared to benign lesions (p < 0.01). Significant associations were found between low levels of CYP4F2 and CYP4F3 and increased age of PDA patients. Interestingly, all isoforms were expressed at higher levels in male patients. CONCLUSIONS: Transcriptional upregulation of cytochrome P450 ω-hydroxylase suggests that these enzymes have the potential to be used as distinguishing markers in pancreatic pathology.

Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to treat less.

The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments are still widely debated. Adjuvant therapies after surgical resection reduce recurrences and contralateral disease, but these treatments have significant financial costs, side effects and there is a group of low-risk patients who would not gain additional benefit. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma treated between 2003 and 2013. Associations between recurrence and demographic factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and treatment modalities (surgery, radiotherapy and endocrine treatment) were assessed. Our single institution register-based study showed that distribution of age at diagnosis and biological features did not significantly differ among ethnic groups. Younger women and micro-invasive carcinoma patients were more likely to undergo mastectomy, while African Americans were more likely to take endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative DCIS were associated with significantly higher recurrence rate. Moreover, we reported a high rate of HER2 positive recurrences, suggesting that expression of this oncogene may represent a potential biomarker for DCIS at high risk of recurrence. To better define the molecular profile of the subgroup at worse prognosis might help to identify biomarkers predictive of recurrence or second tumors, identifying patients candidates for more appropriate treatments.

The effects of test preference, test access, and navigation on colorectal cancer screening.

BACKGROUND: Little is known about how colorectal cancer screening test preferences operate together with test access and navigation to influence screening adherence in primary care. METHODS: We analyzed data from a randomized trial of 945 primary care patients to assess the independent effects of screening test preference for fecal immunochemical test (FIT) or colonoscopy, mailed access to FIT and colonoscopy, and telephone navigation for FIT and colonoscopy, on screening. RESULTS: Preference was not associated with overall screening, but individuals who preferred FIT were more likely to complete FIT screening (P = 0.005), whereas those who preferred colonoscopy were more likely to perform colonoscopy screening (P = 0.032). Mailed access to FIT and colonoscopy was associated with increased overall screening (OR = 2.6, P = 0.001), due to a 29-fold increase in FIT use. Telephone navigation was also associated with increased overall screening (OR = 2.1, P = 0.005), mainly due to a 3-fold increase in colonoscopy performance. We estimated that providing access and navigation for both screening tests may substantially increase screening compared with a preference-tailored approach, mainly due to increased performance of nonpreferred tests. CONCLUSIONS: Preference influences the type of screening tests completed. Test access increases FIT and navigation mainly increases colonoscopy. Screening strategies providing access and navigation to both tests may be more effective than preference-tailored approaches. IMPACT: Preference tailoring in colorectal cancer screening strategies should be avoided if the objective is to maximize screening rates, although other factors (e.g., costs, necessary follow-up) should also be considered.