Patterns of Cancer Care and Association with Survival among Younger Adolescents and Young Adults: A Population-Based Retrospective Cohort Study.

BACKGROUND: Younger adolescents and young adults (AYA) may receive care from either adult or pediatric oncologists. We explored patterns of care in this population and whether survival is associated with provider type. METHODS: Utilizing the California Cancer Registry, we examined a cohort of 9,993 AYAs diagnosed with cancer aged 15 to 24 years from 1999 to 2008. Provider type (adult/pediatric) was determined by individual physician identifiers. For provider type, multivariable logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, diagnosis, and stage. For observed survival, Cox proportional hazard models were additionally adjusted for provider type. ORs and HR with 95% confidence intervals (95% CI) were determined. RESULTS: Most patients saw adult providers (87.3% overall; 72.7% aged 15-19 years). Patients with acute leukemia, sarcoma, and central nervous system (CNS) malignancies more often saw pediatric providers [OR (95% CI) adult versus pediatric 0.48 (0.39-0.59), 0.74 (0.60-0.92), 0.76 (0.60-0.96), respectively]; those with germ cell tumors and other cancers, including carcinomas, more often saw adult providers [2.26 (1.72-2.98), 1.79 (1.41-2.27), respectively]. In aggregate and for most cancers individually, there was no survival difference by provider type [overall HR (95% CI) 1.00 (0.86-1.18)]. Higher survival was associated with pediatric providers for CNS malignancies [1.63 (1.12-2.37)] and rhabdomyosarcoma [2.22 (1.03-4.76)], and with adult providers for non-Hodgkin lymphoma [0.61 (0.39-0.96)]. CONCLUSIONS: Most AYAs 15 to 24 years old are treated by medical oncologists. In general, survival was not associated with provider type. IMPACT: Current patterns of care for this population support increased collaboration between medical and pediatric oncology, including joint clinical trials.

Whole Genome Sequence Analysis of Burkholderia contaminans FFH2055 Strain Reveals the Presence of Putative ß-Lactamases.

Burkholderia contaminans is a member of the Burkholderia cepacia complex (Bcc), a pathogen with increasing prevalence among cystic fibrosis (CF) patients and the cause of numerous outbreaks due to the use of contaminated commercial products. The antibiotic resistance determinants, particularly ß-lactamases, have been poorly studied in this species. In this work, we explored the whole genome sequence (WGS) of a B. contaminans isolate (FFH 2055) and detected four putative ß-lactamase-encoding genes. In general, these genes have more than 93% identity with ß-lactamase genes found in other Bcc species. Two ß-lactamases, a class A (Pen-like, suggested name PenO) and a class D (OXA-like), were further analyzed and characterized. Amino acid sequence comparison showed that Pen-like has 82% and 67% identity with B. multivorans PenA and B. pseudomallei PenI, respectively, while OXA-like displayed strong homology with class D enzymes within the Bcc, but only 22-44% identity with available structures from the OXA family. PCR reactions designed to study the presence of these two genes revealed a heterogeneous distribution among clinical and industrial B. contaminans isolates. Lastly, blaPenO gene was cloned and expressed into E. coli to investigate the antibiotic resistance profile and confers an extended-spectrum ß-lactamase (ESBL) phenotype. These results provide insight into the presence of ß-lactamases in B. contaminans, suggesting they play a role in antibiotic resistance of these bacteria.

Whole-Genome Analysis of an Extensively Drug-Resistance Empedobacter falsenii Strain Reveals Distinct Features and the Presence of a Novel Metallo-ß-Lactamase (EBR-2).

The spread of antibiotic resistance is rapidly threatening the effectiveness of antibiotics in the clinical setting. Many infections are being caused by known and unknown pathogenic bacteria that are resistant to many or all antibiotics currently available. Empedobacter falsenii is a nosocomial pathogen that can cause human infections. E. falsenii Wf282 strain was found to be resistant to many antibiotics, including carbapenems and colistin. Whole-genome shotgun sequencing of the strain was performed, and distinct features were identified. A novel metallo-ß-lactamase, named EBR-2, was found, suggesting a potential role of E. falsenii as a reservoir of ß-lactamases and other resistance determinants also found in its genome. The EBR-2 protein showed the highest catalytic efficiency for penicillin G as compared to meropenem and ampicillin and was unable to hydrolyze cefepime. The results described in this work broaden the current understanding of the role of ß-lactamases in the Flavobacteriaceae family and suggest that E. falsenii Wf282 may be a reservoir of these novel resistance determinants.

Case-linked analysis of clinical trial enrollment among adolescents and young adults at a National Cancer Institute-designated comprehensive cancer center.

BACKGROUND: Poor accrual to cancer clinical trials may contribute to the lower improvement in survival observed for adolescents and young adults (AYAs) (those aged 15-39 years) with cancer. This has been difficult to quantify without reliable mechanisms to link incident cases with study enrollments. Using unique resources available at their National Cancer Institute-designated comprehensive cancer center, the authors compared the percentage of AYAs, children, and older adults enrolled onto cancer clinical trials and determined predictors of enrollment. METHODS: Patients diagnosed with cancer from January 2008 through December 2012 at 1 pediatric and 2 adult University of Southern California hospitals were identified through the California Cancer Registry and individually linked to institutional trial enrollment databases. The availability of clinical trials was assessed. RESULTS: Across the center, the enrollment percentage for AYAs (6%) was equal to that of older adults (6%), but was less than that for children (22%) (P < .01). Within the children's hospital, the AYA enrollment percentage was also less than that for children (15% vs 23%, respectively; P<.01). On multivariate analysis, diagnosis and site of care were found to be predictive of AYA enrollment onto therapeutic and nontherapeutic studies. Hispanic and Asian/Pacific Islander individuals were more likely to enroll onto nontherapeutic studies compared with non-Hispanic whites, but no racial/ethnic difference was observed for therapeutic studies. CONCLUSIONS: In the current study, the percentages of AYAs and older adults enrolled onto therapeutic trials were low but similar. Diagnosis, site of care, and race/ethnicity appear to be predictive of enrollment. Prospective mechanisms must be instituted to capture reasons for nonenrollment of AYAs and develop corrective interventions.

Significant response to oral Etoposide in the treatment of an unresectable cardiac sarcoma.

Primary cardiac sarcomas are rare and carry a poor prognosis. The standard of care is complete resection. Outcomes for patients without complete resection are dismal, and the benefit of adjuvant therapy is uncertain. A 9-year-old girl presented with a large right-sided cardiac mass. After biopsy, the tumor was classified as an undifferentiated sarcoma. Resection was not feasible due to apparent invasion of the right ventricle and atrioventricular groove. Treatment with oral etoposide resulted in a 97% reduction in tumor volume and allowed for complete resection of residual tumor. She is alive with no evidence of disease 25 months from diagnosis.

Lack of impact on polyp detection by fellow involvement during colonoscopy: a meta-analysis.

BACKGROUND: Conflicting data regarding the impact of fellow involvement during colonoscopy on the adenoma detection rate (ADR) and polyp detection rate (PDR) have been reported in the literature. AIMS: Our aim was to perform a meta-analysis to determine the impact of fellow participation during colonoscopy on the ADR and PDR. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, pertinent articles that reported ADR and/or PDR between attending physicians alone compared to gastroenterology fellows with attending physicians were obtained through database searches. Data was abstracted and pooled using a random effects model. The quality of each included study was ascertained using a modified version of the Quality Assessment of Diagnostic Accuracy Studies tool, and potential publication bias was assessed. RESULTS: A total of 14 articles that included 21,504 colonoscopies met the inclusion criteria. The overall PDR and ADR were 44.4 and 30.8%, respectively. No significant differences were found between participant characteristics and colonoscopies performed with or without fellow participation. No significant differences were found in the relative rate of ADR (1.04, 95% CI 0.94-1.15) or PDR (1.03, 95% CI 0.93-1.14) with or without a fellow. An important limitation is that none of the included studies randomized fellow involvement. CONCLUSIONS: Involvement of a fellow during colonoscopy did not affect adenoma and polyp detection rates.

Severe thrombocytopenia in a child secondary to passive platelet antibody transfer from a plasma transfusion.

Although rare, passive transfer of platelet antibodies through blood products can result in thrombocytopenia, acute transfusion reactions, and death. We report a case of severe alloimmune thrombocytopenia from a plasma transfusion. A postliver transplant patient with a normal platelet count received fresh frozen plasma before liver biopsy. Postbiopsy, she developed cardiorespiratory distress, petechiae, and severe thrombocytopenia (platelet count 2000/µL). Her platelet count recovered to normal after 1 week. This diagnosis should be considered whenever an unexpected drop in the platelet count occurs after a plasma-rich transfusion. Conservative transfusion practices and more targeted donor screening may prevent similar events.

Central nervous system involvement at the time of presentation in acute promyelocytic leukemia.

Central nervous system (CNS) involvement is rarely observed in acute promyelocytic leukemia (APML). Most cases of CNS involvement occur at relapse rather than at presentation. Because of the extremely low incidence of CNS disease, diagnostic lumbar puncture is not routinely required and prophylactic intrathecal chemotherapy is not routinely administered. Here, we describe a teenage patient with newly diagnosed APML, chloromas, and symptomatic CNS involvement confirmed by MRI and cerebrospinal fluid (CSF) findings.

Development of photocrosslinkable hyaluronic acid-polyethylene glycol-peptide composite hydrogels for soft tissue engineering.

Hyaluronic acid (HA; also called hyaluronan) is a naturally derived, nonimmunogenic, nonadhesive glycosaminoglycan that has important roles in several wound-healing processes. In previous work, we created photocrosslinkable glycidyl methacrylate-HA (GMHA) hydrogel biomaterials that were cytocompatible, biologically active, and had a decreased rate of hyaluronidase degradation compared with native HA. The goal of the studies presented herein was to explore peptide conjugation techniques to further adjust the material and biological properties of the GMHA hydrogels. We conjugated GMHA with acrylated forms of polyethylene glycol (PEG) and PEG-peptides to yield GMHA-PEG-peptide composite hydrogels. By varying the reactant concentrations, we created stable hydrogels with high peptide conjugation efficiencies (up to 80%), controllable peptide concentrations (in the range of 1-6 micromol peptide per milliliter of hydrogel), and defined physicochemical properties (e.g., swelling ratio, enzymatic degradation rate). These composite hydrogels may prove to be a promising scaffolding biomaterial for a variety of soft tissue engineering applications.