Citations

Background The authors conducted a cluster randomized study to determine the effect of an exportable educational intervention for young women with breast cancer (YWI) on improving care. Methods Sites were randomized 1:1 to the YWI or a contact time control physical activity intervention (PAI) stratified by academic or community site. Up to 15 women aged ≤45 years with newly diagnosed breast cancer were enrolled at each of 14 academic sites and 10 were enrolled at each of 40 community sites. The primary endpoint, attention to fertility, was ascertained by medical record review. Statistical inferences concerning the effect of the intervention used general estimating equations for clustered data. Results A total of 467 patients across 54 sites were enrolled between July 2012 and December 2013. The median age of the patients at the time of diagnosis was 40 years (range, 22‐45 years). Attention to fertility by 3 months was observed in 55% of patients in the YWI and 58% of patients in the PAI ( P = .88). Rates were found to be strongly correlated with age ( P < .0001), and were highest in patients aged <30 years. Attention to genetics was similar (80% in the YWI and 81% in the PAI), whereas attention to emotional health was higher in patients in the YWI (87% vs 76%; estimated odds ratio, 2.63 [95% confidence interval, 1.20‐5.76; P = .016]). Patients rated both interventions as valuable in providing education (64% in the YWI and 63% in the PAI). Conclusions The current study failed to demonstrate differences in attention to fertility with an intervention to improve care for women with breast cancer, although attention to fertility was found to be higher than expected in both groups and emotional health was improved in the YWI group. Greater attention to young women with breast cancer in general may promote more comprehensive care for this population.

Background: Cerebral cavernous malformation is a genetic neurovascular disorder causing aberrant angiogenesis and lesion development within capillary beds. Lesions exhibit impaired endothelial barrier function, causing blood-brain barrier leakage and hemorrhage. Quantitative MRI biomarkers (dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM)) have been shown to correlate with CCM disease progression as measures of barrier leakage and hemorrhagic iron deposition, and there is interest in utilizing these biomarkers as endpoints in clinical trials. However, their consistencies across multiple platforms and institutions has not yet been rigorously verified. Materials and Methods: Instruments used were a 3T Philips Ingenia at University of Chicago and a 3T Siemens Prisma at Northwestern University. QSM was assessed by five balloons filled with varying concentrations of MultiHance, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8, surrounded by an agarose gel. Permeability was assessed by the injection of a bolus of MultiHance through a coiled hose inside a water-filled shell, and the consistency of the peak-to-peak ratio of the curves at the input and output was measured. Each biomarker was assessed by accuracy (to expected values, Pearson correlation), precision (between repeated measurements, paired t-test), and reproducibility (between instruments, paired t-test). Results: QSM measured with an accuracy of r 2 = 0.997 on the Philips Achieva and r 2 = 0.999 on the Siemens Prisma. Each scanner had adequate precision between measurements, showing no significant difference by a paired t-test (p = 0.66 Achieva, p = 0.45 Prisma), and the reproducibility between scanners also showed no significant difference (p = 0.89). The peak-to-peak ratio on DCEQP scans was accurate (r 2 = 0.998), precise between measurements (p = 0.54), and repeatable between instruments (p = 0.49). Conclusion: Quantitative imaging biomarkers DCEQP and QSM are accurate, consistent across multiple measurements, and between platforms and will be useful for future clinical trials in CCM.

OBJECTIVES: Antibiotic prophylaxis is recommended for prevention of the first episode of spontaneous bacterial peritonitis (SBP; primary prophylaxis 1°) and subsequent episodes (secondary prophylaxis 2°). We aimed to compare outcomes in cirrhotic inpatients on 1° vs 2° SBP prophylaxis. METHODS: Data from North American Consortium for the Study of End-Stage Liver Disease were evaluated for cirrhosis details, reasons for admission/medications, inpatient course recorded, and outcomes over 90 days. Outcomes (intensive care units, acute kidney injury, inpatient/90-day mortality) were compared between the 2 groups after propensity-matching on admission model for end-stage liver disease (MELD) score and serum albumin. RESULTS: Among the 2,731 patients enrolled, 305 were on 1° and 187 on 2° SBP prophylaxis. After propensity-matching, 154 patients remained in each group. Patients on 1° prophylaxis were more likely to have admission systemic inflammatory response syndrome ( P = 0.02), with higher intensive care unit admissions (31% vs 21%; P = 0.05) and inpatient mortality (19% vs 9%; P = 0.01) than the 2° prophylaxis group. Patients on 2° prophylaxis had higher total (22% vs 10%; P = 0004), readmission (16% vs 9%; P = 0.03), and nosocomial (6% vs 0.5%; P = 0.01) SBP rates with predominant Gram-negative organisms compared to 1° prophylaxis patients. At 90 days, 1° prophylaxis patients had a higher mortality (35% vs 22%; P = 0.02) and acute kidney injury incidence (48% vs 30%; P = 0.04) compared to 2° prophylaxis patients. DISCUSSION: In this inpatient cirrhosis study, despite prophylaxis, a high proportion of patients developed SBP, which was associated with mortality. Cirrhotic inpatients on 1° prophylaxis had worse outcomes than those on 2° prophylaxis when propensity-matched for the MELD score and serum albumin during the index admission and 90-day follow-up.

AbstractA major challenge in the development of cancer nanomedicine is the inability for nanomaterials to efficiently penetrate and deliver therapeutic agents into solid tumors. Previous studies have shown that tumor vasculature and extracellular matrix regulate the transvascular and interstitial transport of nanoparticles, both critical for successfully delivering nanomedicine into solid tumors. Within the malignant tumor microenvironment, blood vessels are morphologically abnormal and functionally exhibit substantial permeability. Furthermore, the tumor extracellular matrix (ECM), unlike that of the normal tissue parenchyma, is densely packed with collagen. These pathophysiological properties greatly impede intratumoral delivery of nanomaterials. By using an antivascular endothelial growth factor receptor antibody, DC101, and an antitransforming growth factor β1 (TGF‐β1) antibody, normalization of the tumor vasculature and ECM is achieved, respectively, in a syngeneic murine glioma model. This normalization effect results in a more organized vascular network, improves tissue perfusion, and reduces collagen density, all of which contribute to enhanced nanoparticle delivery and distribution within tumors. These findings suggest that combined vascular and ECM normalization strategies can be used to remodel the tumor microenvironment and improve nanomedicine delivery into solid tumors, which has significant implications for developing more effective combinational therapeutic strategies using cancer nanomedicine.

Health care delivery is increasingly evaluated according to quality measures, yet such measures are underdeveloped for cirrhosis. The Practice Metrics Committee of the American Association for the Study of Liver Diseases was charged with developing explicit process‐based and outcome‐based measures for adults with cirrhosis. We identified candidate measures from comprehensive reviews of the literature and input from expert clinicians and patient focus groups. We conducted an 11‐member expert clinician panel and used a modified Delphi method to systematically identify a set of quality measures in cirrhosis. Among 119 candidate measures, 46 were identified as important measures to define the quality of cirrhosis care, including 26 process measures, 7 clinical outcome measures, and 13 patient‐reported outcome measures. The final process measures captured care processes for ascites (n = 5), varices/bleeding (n = 7), hepatic encephalopathy (n = 4), hepatocellular cancer (HCC) screening (n = 1), liver transplantation evaluation (n = 2), and other care (n = 7). Clinical outcome measures included survival, variceal bleeding and rebleeding, early‐stage HCC, liver‐related hospitalization, and rehospitalization within 7 and 30 days. Patient‐reported outcome measures covered physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The final list of patient‐reported outcomes was validated in 79 patients with cirrhosis from nine institutions in the United States. Conclusion: We developed an explicit set of evidence‐based quality measures for adult patients with cirrhosis. These measures are a tool for providers and institutions to evaluate their care quality, drive quality improvement, and deliver high‐value cirrhosis care. The quality measures are intended to be applicable in any clinical care setting in which care for patients with cirrhosis is provided.

Children with pediatric-onset multiple sclerosis and pediatric controls were enrolled across 16 pediatric multiple sclerosis centers in the United States and completed questionnaires that addressed time of first unaided walking and acquisition of 2-word phrases. A total of 467 (308 female) cases and 428 (209 female) controls were enrolled. Pediatric multiple sclerosis (n = 467) were not delayed in walking or using 2-word phrases compared to healthy controls (n = 428) (2.2% vs 5.7%, respectively). Children with disease onset before age 11 versus onset at 11 years or after were more likely to need an individualized education plan ( P = .002), reading assistance ( P = .0003), and math assistance ( P = .001). Children with multiple sclerosis onset prior to age 18 are not delayed in meeting the 2 major early developmental milestones but do have a significantly increased use of special services or learning assistance at school. Further research will need to address whether other measures of development (eg, rate of language acquisition or fine motor skills) differ between pediatric multiple sclerosis and controls.

Background The specificity of the aquaporin-4 antibody to predict recurrent inflammatory central nervous system disease has led to the design of the 2015 neuromyelitis optica spectrum disorder criteria which capture all aquaporin-4 antibody seropositive patients. Objective The purpose of this study was to compare treatment outcomes in aquaporin-4 antibody seropositive patients who met the previous 2006 clinical criteria for neuromyelitis optica with patients who meet the 2015 neuromyelitis optica spectrum disorder criteria. Methods The study involved a three-center retrospective chart review of clinical outcomes among aquaporin-4 patients diagnosed with neuromyelitis optica and neuromyelitis optica spectrum disorder. Results Hazard ratios of relapse during immunosuppressive therapy, relative to pre-therapy, were not significantly different for patients who met the 2006 criteria of neuromyelitis optica versus the 2015 neuromyelitis optica spectrum disorder criteria among those treated with azathioprine ( p = 0.24), mycophenolate mofetil ( p = 0.63), or rituximab ( p = 0.97). Conclusion Reductions in the hazard of relapse during treatment with immunosuppressive therapies, relative to average pre-treatment, were not different for aquaporin-4 antibody seropositive patients categorized using the 2006 criteria of neuromyelitis optica and the 2015 neuromyelitis optica spectrum disorder criteria. These therapeutic findings support the design of the 2015 neuromyelitis optica spectrum disorder criteria which capture all aquaporin-4 antibody seropositive patients.

Abstract The clinical success of immune checkpoint inhibitors in treating metastatic and refractory cancers has generated significant interest in investigating their role in treating locally advanced diseases, thus requiring them to be combined with standard treatments in the hope of producing synergistic antitumor responses. Radiotherapy, in particular, has long been hypothesized to have actions complementary to those of immune checkpoint blockade, and a growing body of evidence indicates that cancer immunotherapy may also have radiosensitizing effects, which would provide unique benefit for locoregional treatments. Recent studies have demonstrated that when immune cells are activated by immunotherapeutics, they can reprogram the tumor microenvironment in ways that may potentially increase the radiosensitivity of the tumor. In this review, we highlight the evidence that supports reciprocal interactions between cancer immunotherapy and radiotherapy, where in addition to the traditional notion that radiation serves to enhance the activation of antitumor immunity, an alternative scenario also exists in which T-cell activation by cancer immunotherapy may sensitize tumors to radiation treatment through mechanisms that include normalization of the tumor vasculature and tissue hypoxia. We describe the empirical observations from preclinical models that support such effects and discuss their implications for future research and trial design.