Incidence and risk factors for graft failure in the modern era of cord blood transplantation.

BACKGROUND AND OBJECTIVES: Graft failure (GF) after cord blood transplant (CBT) has decreased with improved supportive care and cord selection strategies. We aimed to evaluate cord blood selection and factors associated with retransplantation on the incidence of GF, determine risk factors for GF including host antibodies to Kell antigen and evaluate survival after GF. MATERIALS AND METHODS: We retrospectively reviewed 84 patients who underwent CBT at the University of Oklahoma between 2000 and 2016 and compared outcomes in patients with/without engraftment by Day 28. The nonengraftment cohort was further divided into patients who underwent retransplantation. Kaplan-Meier curves with log-rank tests were calculated to assess the association between mortality and engraftment. RESULTS: Engraftment following CBT was high at 81%, with 52% engrafting by Day 28 and an additional 29% engrafting by a median of 36 days. Retransplantation led to 88% engraftment at a median of 53 days. Overall, 75% of the 40 patients who did not engraft by Day 28 died. Female sex and total nucleated cell count < 3.5/kg were significantly associated with lack of engraftment and higher mortality. Antibodies to Kell fetal antigen were not identified. Retransplantation by Day 28 for primary GF conferred a survival advantage. CONCLUSION: This study demonstrates that failure to engraft by 28 days was associated with increased mortality, and risk was mitigated with early retransplantation. Female sex and low total cell dose were associated with increased mortality. Early identification of GF coupled with early retransplantation can reduce mortality in CBT.

Randomized, Double-Blind Trial on the Impact of Word Count in Cancer Clinical Trial Consent Forms.

PURPOSE: This randomized, double-blind study sought to understand whether cancer clinical trial consent form verbosity detracts from patients' decision making on trial enrollment. METHODS: This trial tested mock consent forms of 2,000, 4,000, and 6,000 words. The first two comprised the two experimental arms and the third the control arm. Phase II was conducted to identify the promising arm, which, in phase III, was compared with the control arm. Each consent form described the same trial. Eligible adult patients reported a cancer history and English literacy. The primary end point used a patient-reported Likert scale to assess the relationship between information in the consent form and trial decision making. RESULTS: In phase II, 93 patients were accrued and prompted the selection of the 2,000-word consent form for phase III. In phase III, 182 patients were recruited, resulting in 240 total evaluable patients to compare the 2,000-word versus the 6,000-word arm (control). For the primary end point, 103 (84%) and 107 (91%) patients in the 2,000- and 6,000-word arms, respectively, strongly agreed or agreed with the following: "The information in this consent form helped me make a decision about whether or not to enroll in the trial" (two-sided, P = .14). Median time to read each consent form was 8 and 12 minutes, respectively (two-sided, P < .0001). Among those assigned these consent forms, 84% and 73%, respectively (two-sided, P = .04) signed or expressed a willingness to sign. CONCLUSION: This study's primary end point was not met. However, secondary outcomes suggest a need to further study the efficiency and efficacy of shorter consent forms for cancer clinical trial enrollment.

Understanding Verbosity: Funding Source and the Length of Consent Forms for Cancer Clinical Trials.

Consent forms are an important educational tool that helps cancer patients decide on whether or not to enroll on a clinical trial, but wordiness potentially detracts from their educational value. This single-institution study examined word counts of consent forms for all phase I, II, and III solid tumor clinical trials between 2004 and 2010. Consent forms were categorized by trial funding source: (1) pharmaceutical company; (2) National Clinical Trials Network (NCTN); (3) R01- or other non-government grants; and (4) mixed (funding from multiple sources). Three hundred fifteen consent forms were studied; these included 106 (34%) pharmaceutical company; 145 (46%) NCTN; 44 (14%) R01 type; and 20 (6%) mixed. The overall median word count was 5129 words per consent form (interquartile range (IQR) range, 4226 to 6695). The median word counts per consent form (IQR) were 5648 (4814, 6803), 5243 (4139, 6932), 4365 (3806, 5124), and 4319 (3862, 5944), respectively, based on the above funding sources, showing that pharmaceutical company trial consent forms had the highest median word count. Of note, phase of trial was associated with consent form length (phase III were wordier), and consent forms manifested a consistent increase in wordiness over time. These observations underscore a timely need to find ways to limit the verbosity of consent forms, particularly in those from pharmaceutical company trials.

Principles of Good Clinical Trial Design.

Clinical trials are a fundamental component of medical research and serve as the main route to obtain evidence of the safety and efficacy of treatment before its approval. A trial's ability to provide the intended evidence hinges on appropriate design, background knowledge, trial rationale to sample size, and interim monitoring rules. In this article, we present some general design principles for investigators and their research teams to consider when planning to conduct a trial.

Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study.

BACKGROUND: Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether 18F-fluorothymidine (18F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT. METHODS: Eligible patients were aged 18-55 years, had high-risk haematological malignancies. All patients underwent myeloablation followed by HSCT. The imaging primary endpoint was detection of early subclinical engraftment after HSCT with 18F-FLT PET or CT. Imaging was done 1 day before and 5 or 9, and 28 days, and 1 year after HSCT. This study is registered with ClinicalTrials.gov, number NCT01338987. FINDINGS: Between April 1, 2014, and Dec 31, 2015, 23 patients were enrolled and assessable for toxic effects after completing accrual. 18F-FLT was not associated with any adverse events or delayed engraftment. 18F-FLT imaging objectively identified subclinical bone-marrow recovery within 5 days of HSC infusion, which was up to 20 days before engraftment became clinically evident. Quantitatively, 18F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). 18F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. INTERPRETATION: 18F-FLT allowed quantification and tracking of subclinical bone-marrow repopulation in human beings and revealed new insights into the biology of HSC recovery after HSCT. FUNDING: National Institutes of Health, Ben's Run/Ben's Gift, Albert and Elizabeth Tucker Foundation, Mex Frates Leukemia Fund, Jones Family fund, and Oklahoma Center for Adult Stem Cell Research.

The Development of an HIV Risk Environment Scale of Exotic Dance Clubs.

Exotic dancers have received little research attention despite evidence of high-risk behaviours within exotic dance clubs (EDCs). We developed and assessed the reliability and validity of a risk environment score, examining differences between dancers (n = 107) and other staff (n = 172). In the summer of 2013, anonymous surveys were administered via A-CASI in EDCs (N = 26) in Baltimore among exotic dancers and staff. Surveys consisted of a brief demographic section followed by 65 statements. The overall domain had an alpha = 0.77 and subdomains had the following: social (alpha = 0.87), economic (alpha = 0.92), drug (alpha = 0.89), and policy (alpha = 0.66). In a factor analysis, each domain contributed significantly to the overall latent construct. The results indicate a high level of HIV/STI risk for dancers in EDCs and underscore the need for targeted interventions in these environments. As we continue to unpack the function of the broader environment in STI/HIV risk transmission, the scale could be instructive for other settings.

Trends in Lung and Bronchus, Prostate, Female Breast, and Colon and Rectum Cancers Incidence and Mortality in Oklahoma and the United States from 1999 to 2012.

BACKGROUND: Cancer is the second-leading cause of death in the United States (US) and Oklahoma ranks near the top with the highest rates of mortality from cancer. The top four major sites of cancer were prostate, female breast, lung and bronchus, and colon and rectum. METHODS: Joinpoint software was used to examine the incidence and mortality for the four cancers over time from 1999-2012 for both the US and Oklahoma. RESULTS: Incidence and mortality rates declined from 1999-2012 for the four cancer sites. The average annual, age-adjusted incidence rate was higher in the US than Oklahoma for prostate cancer, but higher in Oklahoma for female breast, lung and bronchus, and colon and rectum cancer sites. CONCLUSIONS: Over the course of 14 years from 1999-2012, the age-adjusted incidence and mortality rates of prostate cancer, female breast cancer, lung and bronchus cancer, and colon and rectum cancer decreased over time nationally and in Oklahoma.

Clinical significance of changes in pB-C2 distance in patients with Chiari Type I malformations following posterior fossa decompression: a single-institution experience.

OBJECT The coexistence of Chiari malformation Type I (CM-I) and ventral brainstem compression (VBSC) has been well documented, but the change in VBSC after posterior fossa decompression (PFD) has undergone little investigation. In this study the authors evaluated VBSC in patients with CM-I and determined the change in VBSC after PFD, correlating changes in VBSC with clinical status and the need for further intervention. METHODS Patients who underwent PFD for CM-I by the senior author from November 2005 to January 2013 with complete radiological records were included in the analysis. The following data were obtained: objective measure of VBSC (pB-C2 distance); relationship of odontoid to Chamberlain's, McGregor's, McRae's, and Wackenheim's lines; clival length; foramen magnum diameter; and basal angle. Statistical analyses were performed using paired t-tests and a mixed-effects ANOVA model. RESULTS Thirty-one patients were included in the analysis. The mean age of the cohort was 10.0 years. There was a small but statistically significant increase in pB-C2 postoperatively (0.5 mm, p < 0.0001, mixed-effects ANOVA). Eleven patients had postoperative pB-C2 values greater than 9 mm. The mean distance from the odontoid tip to Wackenheim's line did not change after PFD, signifying postoperative occipitocervical stability. No patients underwent transoral odontoidectomy or occipitocervical fusion. No patients experienced clinical deterioration after PFD. CONCLUSIONS The increase in pB-C2 in patients undergoing PFD may occur as a result of releasing the posterior vector on the ventral dura, allowing it to relax posteriorly. This increase appears to be well-tolerated, and a postoperative pB-C2 measurement of more than 9 mm in light of stable craniocervical metrics and a nonworsened clinical examination does not warrant further intervention.

AN AUTOMATIC 3D CT/PET SEGMENTATION FRAMEWORK FOR BONE MARROW PROLIFERATION ASSESSMENT.

Clinical assessment of bone marrow is limited by an inability to evaluate the marrow space comprehensively and dynamically and there is no current method for automatically assessing hematopoietic activity within the medullary space. Evaluating the hematopoietic space in its entirety could be applicable in blood disorders, malignancies, infections, and medication toxicity. In this paper, we introduce a CT/PET 3D automatic framework for measurement of the hematopoietic compartment proliferation within osseous sites. We first perform a full-body bone structure segmentation using 3D graph-cut on the CT volume. The vertebrae are segmented by detecting the discs between adjacent vertebrae. Finally, we register the bone marrow CT volume with its corresponding PET volume and capture the spinal bone marrow volume. The proposed framework was tested on 17 patients, achieving an average accuracy of 86.37% and a worst case accuracy of 82.3% in automatically extracting the aggregate volume of the spinal marrow cavities.

Patterns and risk factors of inconsistent condom use among men who have sex with men in Viet Nam: Results from an Internet-based cross-sectional survey.

Survey data from men who have sex with men (MSM) in Asian cities indicate drastic increases in HIV prevalence. It is unknown which factors are most important in driving these epidemics. The objective of this study was to identify patterns of condom use among MSM Internet users living in Viet Nam, as well as risk factors associated with inconsistent condom use and non-condom use. A national Internet-based survey of sexual behaviours was administered in 2011. Results showed that 44.9% of MSM reported not using a condom during their last anal sex encounter with a male partner. MSM were less likely to report condom use during anal sex with long-term partners than with casual partners. Twenty-three and a half per cent of MSM surveyed had ever taken an HIV test and received the results. Study findings highlight the urgent need for targeted strategies focused on increasing the rate of consistent condom use during anal sex with male partners among MSM in Viet Nam.

'Never testing for HIV' among men who have sex with men in Viet Nam: results from an Internet-based cross-sectional survey.

BACKGROUND: Men who have sex with men in Viet Nam have been under-studied as a high-risk group for HIV infection, and this population's percentage and determinants of HIV testing have not been comprehensively investigated. METHODS: A national Internet-based survey of self-reported sexual and health seeking behaviours was conducted between August and October 2011 with 2077 Vietnamese men who had sex with men in the last twelve months to identify the frequency of 'never testing for HIV' among Internet-using MSM living in Viet Nam, as well as the factors associated with this HIV-related high-rish behavior. Logistic regression analyses were conducted to assess the demographic characteristics and behaviours predicting never testing for HIV. RESULTS: A total of 76.5% of men who have sex with men who were surveyed reported never having been voluntarily tested for HIV. Predictors of never being tested included having a monthly income less than VND 5 Million, being a student, using the Internet less than 15 hour per week, and not participating in a behavioural HIV intervention. CONCLUSIONS: Never testing for HIV is common among Internet-using men who have sex with men in Viet Nam. Given the dangerously high prevalence of this high-risk behaviour, our findings underscore the urgent need for segmented and targeted HIV prevention, care and treatment strategies, focusing on drastically reducing the number of men who have sex with men never testing for HIV in Viet Nam.

Evaluation of lymphangiogenic factors, vascular endothelial growth factor D and E-cadherin in distinguishing inflammatory from locally advanced breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer that on presentation resembles locally advanced breast cancer (LABC). This study identified molecular features of IBC and LABC to investigate pathogenesis. MATERIALS AND METHODS: This study involved 100 IBC cases identified in a national IBC registry and 107 non-IBC LABC cases from the National Cancer Institute's Cooperative Breast Cancer Tissue Resource (CBCTR). Vascular endothelial growth factor D (VEGF-D) and E-cadherin levels and lymphatic vessel density (LVD) measured by podoplanin staining were examined by immunohistochemistry on paraffin-embedded tumor specimens. Intralymphatic tumor emboli (ILTE) were assessed in IBC and non-IBC tumors. IBC cases diagnosed by clinicians but not meeting the case definitions of the American Joint Committee on Cancer (AJCC) or the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI)(designated atypical IBC) were compared with AJCC- and/or SEER-defined cases (designated classic IBC). RESULTS: E-cadherin levels were significantly higher in classic IBC cases compared with non-IBC cases (P = .031), whereas compared with classic IBC, patients with non-IBC LABC had significantly higher LVD (P = .0017) and VEGF-D levels (P < .0001). ILTE was marginally greater in classic IBC than in non-IBC (P = .046). The profile of laboratory values in atypical IBC cases more closely resembled those fitting classic IBC than LABC. CONCLUSION: E-cadherin levels, LVD, VEGF-D expression, and to a lesser extent, ILTE differed between classic IBC and non-IBC LABC. The similarity of laboratory results between atypical IBC and classic IBC vs. LABC suggests the need for broadening both the AJCC and SEER case definitions for this disease.