The Impact of Peripheral Intravenous Catheter Insertion Technique and Catheter-to-Vein Ratio on Postinsertion Failure.

BACKGROUND: Peripheral intravenous catheter (PIVC) postinsertion failure rates are unacceptable. Ultrasonography is an adjunctive tool that may improve PIVC utilization success. OBJECTIVES: Determine if ultrasonographically guided (USG) PIVCs placed in the emergency department (ED) significantly decreases postinsertion failure rate, increases utility time, and decreases postremoval complication rate. Determine if catheter-to-vein ratio (CVR) predicts postinsertion failure. METHODS: Participants were randomized to either standard or USG cohort. Data collection included participant and PIVC characteristics, vein measurements, postinsertion failure, and postremoval complication. Chi-square analysis compared postinsertion failure rates. Group t-test compared utility times. Postremoval complication rates were compared with standard rate analysis. The receiver operating characteristic curve was calculated to determine if CVR could predict postinsertion failure. An enrollment of 582 was estimated. RESULTS: A total of 223 patients were enrolled, with 222 PIVCs investigated. Standard cohort included 116 PIVCs and USG cohort included 106 PIVCs. A total of 212 vein diameters were analyzed. USG PIVC insertion did not result in fewer postinsertion failures (p = 0.654) or longer utility time (p = 0.808). Postremoval complications were not significantly lower (p = 0.414). Receiver operating characteristic curve showed a cut-off CVR of ∼ 0.21. Area under the curve was 0.621 (p = 0.063, 95% confidence interval 0.508-0.734). CONCLUSION: The USG technique did not decrease postinsertion failure rate, increase utility time, or significantly decrease postremoval complication rate. A CVR predictive of postinsertion failure could not be determined.

DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.

Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized. Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants. Design, Setting, and Participants: In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research. Exposure: Centralized DNA sequencing of banked pretransplant remission blood samples. Main Outcomes and Measures: The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models. Results: Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P < .001) and decreased survival at 3 years (39% vs 63%; difference, -24% [2-sided 95% CI, -39% to -9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P < .001). Conclusions and Relevance: Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia.

Synthesis of NaA zeolite from foundry dust and its adsorption capacity of ammonia.

Eutrophication of water bodies due to excess ammonia nitrogen (NH4+-N) is harmful to aquatic organisms and human health. In this study, foundry dust (FD) from foundry industry was used to synthesize NaA zeolite to use as an adsorbent to remove NH4+-N from wastewater. Results demonstrate that FD could be successfully synthesized to form a foundry dust-based NaA zeolite (FZA) through adjustment of the silica-alumina ratio of n (SiO2)/n (Al2O3) at 2 at 95 °C. Specific surface area, total pore volume, and cation exchange capacity (CEC), and maximum adsorption NH4+-N of FZA was respectively 43.185 cm2/g, 0.0364 cm3/g, 212.35 mmol/100 g and 37.81 mg/g, which was 4.74, 1.54, 1.52 and 1.62 times as much as the NaA zeolite (SZA). FZA with higher adsorption NH4+-N capacity was related to higher specific surface area and CEC. The NH4+-N adsorption amount of 28.57 mg/g by FZA was obtained after the fourth regeneration, which was notably higher than that of SZA (23.27 mg/g). The desorption rate of NH4+-N from FZA was 87% by the fourth regeneration. FZA effectively removed NH4+-N from swine wastewater containing 153.32 mg/L NH4+-N. Results suggest that FZA could be used as absorbent to removal NH4+-N from wastewater.

Randomized multicenter trial of sirolimus vs prednisone as initial therapy for standard-risk acute GVHD: the BMT CTN 1501 trial.

Clinical- and biomarker-based tools may identify a lower-risk acute graft-versus-host disease (GVHD) population amenable to novel, reduced-intensity treatments. Previous data suggest sirolimus may rival standard of care prednisone. We conducted a National Heart, Lung, and Blood Institute/National Cancer Institute-funded Blood and Marrow Transplant Clinical Trials Network multicenter, open-label, randomized phase 2 trial to estimate the difference in day 28 complete response (CR)/partial response (PR) rates for sirolimus vs prednisone as initial treatment of patients with standard risk (SR) acute GVHD as defined by the Minnesota (MN) GVHD Risk Score and Ann Arbor (AA1/2) biomarker status. A total of 127 MN-SR patients were randomized (1:1), and 122 were AA1/2 (sirolimus, n = 58; prednisone, n = 64). Others were AA3 (n = 4), or AA status missing (n = 1). The day 28 CR/PR rates were similar for sirolimus 64.8% (90% confidence interval [CI], 54.1%-75.5%) vs 73% (90% CI, 63.8%-82.2%) for prednisone. The day 28 rate of CR/PR with prednisone ≤0.25 mg/kg/day was significantly higher for sirolimus than prednisone (66.7% vs 31.7%; P < .001). No differences were detected in steroid-refractory acute GVHD, disease-free survival, relapse, nonrelapse mortality, or overall survival. Sirolimus was associated with reduced steroid exposure and hyperglycemia, reduced grade 2 to 3 infections, improvement in immune suppression discontinuation and patient-reported quality of life, and increased risk for thrombotic microangiopathy. For patients with clinical- and biomarker-based SR acute GVHD, sirolimus demonstrates similar overall initial treatment efficacy as prednisone. In addition, sirolimus therapy spares steroid exposure and allied toxicity, does not compromise long-term survival outcomes, and is associated with improved patient-reported quality of life. This trial was registered at www.clinicaltrials.gov as #NCT02806947.

Inverted channel variations identified on a distal portion of a bajada in the central Atacama Desert, Chile.

In deserts, the interplay between occasional fluvial events and persistent aeolian erosion can form composite modern and relict surfaces, especially on the distal portion of alluvial fans. There, relief inversion of alluvial deposits by differential erosion can form longitudinal ridges. We identified two distinct ridge types formed by relief inversion on converging alluvial fans in the hyperarid Chilean Atacama Desert. Although they are co-located and similar in scale, the ridge types have different ages and formation histories that apparently correspond to minor paleoclimate variations. Gravel-armored ridges are remnants of deflated alluvial deposits with a bimodal sediment distribution (gravel and sand) dated to a minor pluvial phase at the end of the Late Pleistocene (~12 kyr). In contrast, younger (~9 kyr) sulfate-capped ridges formed during a minor arid phase with evaporite deposition in a pre-existing channel that armored the underlying deposits. Collectively, inverted channels at Salar de Llamara resulted from multiple episodes of surface overland flow and standing water spanning several thousand years. Based on ridge relief and age, the minimum long-term deflation rate is 0.1-0.2 m/kyr, driven primarily by wind erosion. This case study is an example of the equifinality concept whereby different processes lead to similar landforms. The complex history of the two ridge types can only be generally constrained in remotely sensed data. In situ observations are required to discern the specifics of the aqueous history, including the flow type, magnitude, sequence, and paleoenvironment. These findings have relevance for interpreting similar landforms on Mars.

Follistatin and Soluble Endoglin Predict 1-Year Nonrelapse Mortality after Allogeneic Hematopoietic Cell Transplantation.

Damage-associated angiogenic factors (AFs), including follistatin (FS) and soluble endoglin (sEng), are elevated in circulation at the onset of acute graft-versus-host disease (GVHD). We hypothesized that regimen-related tissue injury also might be associated with aberrant AF levels and sought to determine the relevance of these AF on nonrelapse mortality (NRM) in patients with acute GVHD and those without acute GVHD. To test our hypothesis, we analyzed circulating levels of FS, sEng, angiopoietin-2 (Ang2), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) A and B, placental growth factor (PlGF), and soluble VEGF receptor (sVEGFR)-1 and -2, in plasma samples from patients enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402 (n = 221), which tested GVHD prophylaxis after myeloablative hematopoietic stem cell transplantation (HCT). We found that the interaction between FS and sEng had an additive effect in their association with 1-year NRM. In multivariate analysis, patients with the highest levels of day +28 FS and sEng had a 14.9-fold greater hazard ratio (HR) of NRM (95% confidence interval, 3.2 to 69.4; P < .01) when compared with low levels of FS and sEng. We validated these findings using an external cohort of patients (n = 106). Pre-HCT measurements of FS and sEng were not associated with NRM, suggesting that elevations in these factors early post-HCT may be consequences of early regimen-related toxicity. Determining the mechanisms responsible for patient-specific vulnerability to treatment toxicities and endothelial damage associated with specific AF elevation may guide interventions to reduce NRM post-HCT.

Summary of the 2019 Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup has organized an annual workshop focused on minimal residual disease (MRD) testing and immune profiling (IP) in multiple myeloma since 2016. In 2019, the workshop took place as an American Society of Hematology (ASH) Friday Scientific Workshop titled "Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma." This workshop focused on 4 main topics: the molecular and immunologic evolution of plasma cell disorders, development of new laboratory- and imaging-based MRD assessment approaches, chimeric antigen receptor T cell therapy research, and statistical and regulatory issues associated with novel clinical endpoints. In this report, we provide a summary of the workshop and discuss future directions.

Cranial burr holes in the emergency department: to drill or not to drill?

The practice of trepanning (referred to today as a craniotomy) dates back to the Neolithic period. Reasons for drilling a hole through the skull evolved from releasing evil spirits and curing insanity to practical management of head injuries in ancient Greece and Rome. Today, craniotomy or drilling a burr hole through the skull is very much the purview of the neurosurgeon. Yet one could argue that the procedure itself is more 'bone surgery' than 'brain surgery'. Nevertheless, despite the fact that head injury is a common presentation at district general hospitals and traumatic extra-axial haemorrhages are encountered often, the straightforward skillset required to drill a burr hole as a pretransfer, temporising, life-saving measure is seldom taught and has never gained traction. What we advocate in this article is the adaptation and novel application of an old, tried and tested technique in new hands. The critical pathophysiological turning point of any expanding extra-axial haemorrhage is the inflection point on the volume/Intracranial pressure (ICP) curve beyond which compensation is impossible. The subsequent rising ICP initiates a predictable continuum of clinical signs signalling progressive herniation. There are few emergencies as time-critical as a patient with an isolated, expanding extradural haemorrhage embarking on a trajectory of rostrocaudal deterioration and inevitable death. In many cases, the tragedy is compounded by the knowledge that such a patient probably has a healthy underlying brain, often evidenced by a lucid period after trauma. Our emergency department is attached to a small 300-bed District General Hospital (DGH) on the rural North West coast of Ireland. We are 262 km distant by road from a national neurosciences department that can, at best, be reached in 2 hours and 30 min. Quality improvement review of years of dismal outcomes in patients such as those described earlier with potentially remediable pathology prompted research and development of the skillset we are now able to offer, an old technique in new hands.

Grading meningiomas utilizing multiparametric MRI with inclusion of susceptibility weighted imaging and quantitative susceptibility mapping.

BACKGROUND AND PURPOSE: The ability to predict high-grade meningioma preoperatively is important for clinical surgical planning. The purpose of this study is to evaluate the performance of comprehensive multiparametric MRI, including susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) in predicting high-grade meningioma both qualitatively and quantitatively. METHODS: Ninety-two low-grade and 37 higher grade meningiomas in 129 patients were included in this study. Morphological characteristics, quantitative histogram analysis of QSM and ADC images, and tumor size were evaluated to predict high-grade meningioma using univariate and multivariate analyses. Receiver operating characteristic (ROC) analyses were performed on the morphological characteristics. Associations between Ki-67 proliferative index (PI) and quantitative parameters were calculated using Pearson correlation analyses. RESULTS: For predicting high-grade meningiomas, the best predictive model in multivariate logistic regression analyses included calcification (ß=0.874, P=0.110), peritumoral edema (ß=0.554, P=0.042), tumor border (ß=0.862, P=0.024), tumor location (ß=0.545, P=0.039) for morphological characteristics, and tumor size (ß=4×10-5, P=0.004), QSM kurtosis (ß=-5×10-3, P=0.058), QSM entropy (ß=-0.067, P=0.054), maximum ADC (ß=-1.6×10-3, P=0.003), ADC kurtosis (ß=-0.013, P=0.014) for quantitative characteristics. ROC analyses on morphological characteristics resulted in an area under the curve (AUC) of 0.71 (0.61-0.81) for a combination of them. There were significant correlations between Ki-67 PI and mean ADC (r=-0.277, P=0.031), 25th percentile of ADC (r=-0.275, P=0.032), and 50th percentile of ADC (r=-0.268, P=0.037). CONCLUSIONS: Although SWI and QSM did not improve differentiation between low and high-grade meningiomas, combining morphological characteristics and quantitative metrics can help predict high-grade meningioma.

Effect of Sirolimus on Immune Reconstitution Following Myeloablative Allogeneic Stem Cell Transplantation: An Ancillary Analysis of a Randomized Controlled Trial Comparing Tacrolimus/Sirolimus and Tacrolimus/Methotrexate (Blood and Marrow Transplant Clinical Trials Network/BMT CTN 0402).

Although allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for hematologic neoplasms, one of its limiting toxicities continues to be graft-versus-host disease, both acute (aGVHD) and chronic (cGVHD). Sirolimus is a mammalian target of rapamycin inhibitor that has proven effective in GVHD prophylaxis in combination with a calcineurin inhibitor, such as tacrolimus. The impact of sirolimus on immune reconstitution has not been comprehensively investigated in vivo thus far, however. Here we present an ancillary analysis of the randomized study BMT-CTN 0402 that examined the effect of sirolimus on immune subsets post-transplantation. We further examine the association between different lymphocyte subsets and outcomes post-transplantation in each arm. BMT-CTN 0402 was a randomized trial (n = 304) comparing 2 GVHD prophylaxis regimens, tacrolimus/sirolimus (Tac/Sir) and tacrolimus/methotrexate (Tac/MTX), in patients with acute myelogenous leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome undergoing myeloablative HLA-matched HCT. There were no differences in 114-day GVHD-free survival (primary endpoint), aGVHD, cGVHD, relapse, or overall survival (OS) between the 2 arms. Of the 304 patients, 264 had available samples for the current immune reconstitution analysis. Blood samples were collected at 1, 3, 6, 12, and 24 months post-HCT. Multiparameter flow cytometry was performed at the project laboratory (Esoterix Clinical Trials Services) in a blinded fashion, and results for the 2 arms were compared. Multivariable Cox regression models, treating each phenotypic parameter as a time-dependent variable, were constructed to study the impact of reconstitution on clinical outcomes. There were no significant differences in patient and transplantation characteristics between the Tac/Sir and Tac/MTX arms in this analysis. Absolute lymphocyte count and CD3+ cell, CD4+ cell, and conventional T cell (Tcon) counts were significantly decreased in the Tac/Sir arm for up to 3 months post-HCT, whereas CD8+ cells recovered even more slowly (up to 6 months) in this arm. Interestingly, there was no clear difference in the absolute number of regulatory T cells (Tregs, defined as CD4+CD25+ cells) between the 2 arms at any point post-HCT; however, the Treg:Tcon ratio was significantly greater in the Tac/Sir arm in the first 3 months after HCT. B lymphocyte recovery was significantly compromised in the Tac/Sir arm from 1 month to 6 months after HCT, whereas natural killer cell reconstitution was not affected in the Tac/Sir arm. In the outcomes analysis, higher numbers of CD3+ cells, CD4+ cells, CD8+ cells, and Tregs were associated with better OS. Neither Treg numbers nor the Treg:Tcon ratio was correlated with GVHD. Our findings indicate that Tac/Sir has a more profound T cell suppressive effect than the combination of Tac/MTX in the early post-transplantation period, and particularly compromises the recovery of CD8+ T cells, which have been implicated in aGVHD. Sirolimus used in vivo with tacrolimus does not appear to result in increased absolute numbers of Tregs, but might have a beneficial effect on the Treg:Tcon balance in the first 3 months after transplantation. Nonetheless, no differences in aGVHD or cGVHD between the 2 arms were observed in the parent randomized trial. Calcineurin-inhibitor free, sirolimus-containing GVHD prophylaxis strategies, incorporating other novel agents, should be investigated further to maximize the potential favorable effect of sirolimus on Treg:Tcon balance in the post-transplantation immune repertoire. Sirolimus significantly compromises B cell recovery in the first 6 months post-HCT, with potential complex effects on cGVHD that merit further study.

Summary of the Second Annual BMT CTN Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.

The second annual Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was convened on December 7, 2017, at the American Society of Hematology (ASH) meeting. During this workshop, investigators from around the world presented their latest research involving assessment of minimal residual disease (MRD) and immune profiling (IP) in myeloma. This document summarizes the workshop presentations as well as relevant ASH abstracts and focuses on the regulatory issues involved in the integration of MRD and IP assessment in clinical trial design and practice.

Allogeneic Hematopoietic Cell Transplant for HIV Patients with Hematologic Malignancies: The BMT CTN-0903/AMC-080 Trial.

We set out to assess feasibility and safety of allogeneic hematopoietic cell transplant in 17 persons with HIV in a phase II prospective multicenter trial. The primary endpoint was 100-day nonrelapse mortality (NRM). Patients had an 8/8 HLA-matched related or at least a 7/8 HLA-matched unrelated donor. Indications for transplant were acute leukemia, myelodysplasia, and lymphoma. Conditioning was myeloablative or reduced intensity. There was no NRM at 100 days. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 41%. At 1 year, overall survival was 59%; deaths were from relapsed/progressive disease (n = 5), acute GVHD (n = 1), adult respiratory distress syndrome (n = 1), and liver failure (n = 1). In patients who achieved complete chimerism, cell-associated HIV DNA and inducible infectious virus in the blood were not detectable. Blood and Marrow Transplant Clinical Trials Network 0903/AIDS Malignancy Consortium 080 was registered at www.clinicaltrials.gov (no. NCT01410344).

Texture analysis on conventional MRI images accurately predicts early malignant transformation of low-grade gliomas.

OBJECTIVES: Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. This study aimed to evaluate the feasibility of texture analysis on preoperative conventional MRI images in predicting early malignant transformation from low- to high-grade glioma and compare its utility to histogram analysis alone. METHODS: A total of 68 patients with low-grade glioma (LGG) were included in this study, 15 of which showed malignant transformation. Patients were randomly divided into training (60%) and testing (40%) sets. Texture analyses were performed to obtain the most discriminant factor (MDF) values for both training and testing data. Receiver operating characteristic (ROC) curve analyses were performed on MDF values and 9 histogram parameters in the training data to obtain cutoff values for determining the correct rates of discrimination between two groups in the testing data. RESULTS: The ROC analyses on MDF values resulted in an area under the curve (AUC) of 0.90 (sensitivity 85%, specificity 84%) for T2w FLAIR, 0.92 (86%, 94%) for ADC, 0.96 (97%, 84%) for T1w, and 0.82 (78%, 75%) for T1w + Gd and correctly discriminated between the two groups in 93%, 100%, 93%, and 92% of cases in testing data, respectively. In the astrocytoma subgroup, AUCs were 0.92 (88%, 83%) for T2w FLAIR and 0.90 (92%, 74%) for T1w + Gd and correctly discriminated two groups in 100% and 92% of cases. The MDF outperformed all 9 of the histogram parameters. CONCLUSION: Texture analysis on conventional preoperative MRI images can accurately predict early malignant transformation of LGGs, which may guide therapeutic planning. KEY POINTS: • Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. • Texture analysis based on conventional preoperative MR images can accurately predict early malignant transformation from low- to high-grade glioma. • Texture analysis is a clinically feasible technique that may provide an alternative and effective way of determining the likelihood of early malignant transformation and help guide therapeutic decisions.

Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS.

Neurons are particularly vulnerable to perturbations in endo-lysosomal transport, as several neurological disorders are caused by a primary deficit in this pathway. In this report, we used positional cloning to show that the spontaneously occurring neurological mutation teetering (tn) is a single nucleotide substitution in hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT). The tn mice exhibit hypokenesis, muscle weakness, reduced muscle size and early perinatal lethality by 5-weeks of age. Although HGS has been suggested to be essential for the sorting of ubiquitinated membrane proteins to the lysosome, there were no alterations in receptor tyrosine kinase levels in the central nervous system, and only a modest decrease in tropomyosin receptor kinase B (TrkB) in the sciatic nerves of the tn mice. Instead, loss of HGS resulted in structural alterations at the neuromuscular junction (NMJ), including swellings and ultra-terminal sprouting at motor axon terminals and an increase in the number of endosomes and multivesicular bodies. These structural changes were accompanied by a reduction in spontaneous and evoked release of acetylcholine, indicating a deficit in neurotransmitter release at the NMJ. These deficits in synaptic transmission were associated with elevated levels of ubiquitinated proteins in the synaptosome fraction. In addition to the deficits in neuronal function, mutation of Hgs resulted in both hypermyelinated and dysmyelinated axons in the tn mice, which supports a growing body of evidence that ESCRTs are required for proper myelination of peripheral nerves. Our results indicate that HGS has multiple roles in the nervous system and demonstrate a previously unanticipated requirement for ESCRTs in the maintenance of synaptic transmission.

Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT).

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial.

BACKGROUND: Voriconazole is a first-line agent for the prevention and treatment of a number of invasive fungal diseases. Relatively little is known about the relationship between drug exposure and the prevention of invasive fungal infections. PATIENTS AND METHODS: A pharmacokinetic-pharmacodynamic substudy was performed as part of the BMT CTN 0101 trial, which was a randomized clinical trial comparing voriconazole with fluconazole for the prevention of invasive fungal infections in HSCT recipients. A previously described population pharmacokinetic model was used to calculate the maximum a posteriori Bayesian estimates for 187 patients. Drug exposure in each patient was quantified in terms of the average AUC and average trough concentrations. The relationship between drug exposure and the probability of breakthrough infection was investigated using logistic regression. AUC and trough concentrations in patients with and without breakthrough infection were compared. RESULTS: Pharmacokinetic data from each patient were readily described using the maximum a posteriori Bayesian estimates. There were only five patients that had a breakthrough infection while receiving voriconazole in the first 100 days post-HSCT. For these patients, there was no statistically significant relationship between the average AUC or average trough concentration and the probability of breakthrough infection [OR (95% CI) 1.026 (0.956-1.102) and 1.108 (0.475-2.581), respectively]. P value for these estimates was 0.474 and 0.813, respectively. CONCLUSIONS: Given the very small number of proven/probable infections, it was difficult to identify any differences in drug exposure in HSCT recipients with and without breakthrough fungal infections.

Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration.

PURPOSE: Our aim was to investigate the macular response to three different supplements containing lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) in normal subjects and those with age-related macular degeneration (AMD). MATERIALS AND METHODS: Macular pigment optical density (MPOD) and serum xanthophyll concentrations were measured in normal (n = 31) and AMD subjects (n = 32), randomly assigned to: group 1 (20 mg L, 2 mg Z, 0.3 mg MZ), group 2 (10 mg L, 2 mg Z, 10 mg MZ) or group 3 (3 mg L, 2 mg Z, 17 mg MZ). MPOD was measured at baseline, 2, 4, 6 and 8 weeks and at 0.25°, 0.5°, 1.0° and 1.75° of eccentricity using customised heterochromatic flicker photometry and serum xanthophylls by HPLC. RESULTS: MPOD increased significantly at all eccentricities in each group (p < 0.05), except at 1.75° in group 3 (p = 0.242). There was no difference in MPOD measurements between AMD and normal subjects, except for group 2, where AMD subjects exhibited a greater response at 1.75° (p = 0.012). Final serum concentrations of MZ were positively and significantly related to final MPOD values at each eccentricity in all subjects. Targeted analysis of those subjects receiving the MZ-containing supplements exhibited stronger relationships between serum MZ concentrations and MPOD at 0.25° in group 3 than group 2; in group 2 all associations were positive, but only significant at 1.75°. CONCLUSIONS: Serum concentrations of MZ were strongly correlated with MPOD after 8 weeks of supplementation with the group 3 formulation, but the inclusion of L in the group 2 formulation may result in greater MPOD augmentation across the spatial profile.

Measles epidemics of variable lethality in the early 20th century.

Until the mid-20th century, mortality rates were often very high during measles epidemics, particularly among previously isolated populations (e.g., islanders), refugees/internees who were forcibly crowded into camps, and military recruits. Searching for insights regarding measles mortality rates, we reviewed historical records of measles epidemics on the Polynesian island of Rotuma (in 1911), in Boer War concentration camps (in 1900-1902), and in US Army mobilization camps during the First World War (in 1917-1918). Records classified measles deaths by date and clinical causes; by demographic characteristics, family relationships (for Rotuma islanders and Boer camp internees), and prior residences; and by camp (for Boer internees and US Army recruits). During the Rotuman and Boer War epidemics, measles-related mortality rates were high (up to 40%); however, mortality rates differed more than 10-fold across camps/districts, even though conditions were similar. During measles epidemics, most deaths among camp internees/military recruits were due to secondary bacterial pneumonias; in contrast, most deaths among Rotuman islanders were due to gastrointestinal complications. The clinical expressions, courses, and outcomes of measles during first-contact epidemics differ from those during camp epidemics. The degree of isolation from respiratory pathogens other than measles may significantly determine measles-related mortality risk.

Evaluation of peripheral blood stem cell quality in products transported by traditional courier or commercial overnight shipping services.

BACKGROUND: Peripheral blood stem cell (PBSC) products have traditionally been transported from the collection center to a transplant center using validated volunteer courier-based procedures. Evolving airline service strategies and security policies have complicated this model of product transport. This study was designed to evaluate the feasibility of transporting PBSC products using commercial overnight shipping services, while maintaining product quality, compared to courier-transported products. STUDY DESIGN AND METHODS: Five PBSC products were collected from healthy volunteer donors and divided to evaluate product quality when transported either by volunteer courier or by commercial overnight shipping service. Products were evaluated on the day of collection and at 24, 48, and 72 hours postcollection for total nucleated cell (TNC) count, cell viability, progenitor cell numbers, and progenitor cell lineage growth potential (colony-forming units [CFUs]) to assess product composition and quality associated with each cohort. RESULTS: No delivery delays were encountered and all products were received intact. Measurements of product composition and quality demonstrated no differences in TNC count (p=0.893), cell viability (p=0.409), CD34+ progenitor cell content (p=0.509), or CFU-granulocyte-macrophage growth potential (p=0.827). CONCLUSIONS: We found no difference in product viability, progenitor cell content, or product potency in PBSC products transported either by volunteer courier or by commercial overnight shipping.