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.

Workflow Analysis Driven Recommendations for Integration of Electronically-Enhanced Sexually Transmitted Infection Screening Tools in Pediatric Emergency Departments.

Adolescents are disproportionately affected by sexually transmitted infections (STIs). Failure to diagnose and treat STIs in a timely manner may result in serious sequelae. Adolescents frequently access the emergency department (ED) for care. Although ED-based STI screening is acceptable to both patients and clinicians, understanding how best to implement STI screening processes into the ED clinical workflow without compromising patient safety or efficiency is critical. The objective of this study was to conduct direct observations documenting current workflow processes and tasks during patient visits at six Pediatric Emergency Care Applied Research Network (PECARN) EDs for site-specific integration of STI electronically-enhanced screening processes. Workflow observations were captured via TaskTracker, a time and motion electronic data collection application that allows researchers to categorize general work processes and record multitasking by providing a timestamp of when tasks began and ended. Workflow was captured during 118 patient visits across six PECARN EDs. The average time to initial assessment by the most senior provider was 76 min (range 59-106 min, SD = 43 min). Care teams were consistent across sites, and included attending physicians, advanced practice providers, nurses, registration clerks, technicians, and students. A timeline belt comparison was performed. Across most sites, the most promising implementation of a STI screening tool was in the patient examination room following the initial patient assessment by the nurse.

Timeliness and quality of surgical discharge summaries after the implementation of an electronic format.

BACKGROUND: As electronic discharge summaries (EDS) become more prevalent and health care systems increase their focus on transitions of care, analysis of EDS quality is important. The objective of this study was to assess the timeliness and quality of EDS compared with dictated summaries for surgical patients, which has not previously been evaluated. METHODS: A retrospective study was conducted of a sample of discharge summaries from surgical patients at an urban university teaching hospital before and after the implementation of an EDS program. Summaries were evaluated on several dimensions, including time to summary completion, summary length, and summary quality, which was measured on a 13-item scoring tool. RESULTS: After the exclusion of 5 patients who died, 195 discharge summaries were evaluated. Discharge summaries before and after EDS implementation were similar in admission types and discharge destinations of the patients. Compared with dictated summaries, EDS had equivalent overall quality (P = .11), with higher or equivalent scores on all specific quality aspects except readability. There was a highly significant statistical and clinical improvement in timeliness for electronic summaries (P < .01). Obvious use of copying and pasting was identified in 8% of discharge summaries and was associated with decreased readability (P = .02). CONCLUSIONS: The implementation of EDS can improve the timeliness of summary completion without sacrificing quality for surgical patients. Excessive copying and pasting can reduce the readability of discharge summaries, and strategies to discourage this practice without the use of appropriate editing should be used.

Plasma membrane potential oscillations in insulin secreting Ins-1 832/13 cells do not require glycolysis and are not initiated by fluctuations in mitochondrial bioenergetics.

Oscillations in plasma membrane potential play a central role in glucose-induced insulin secretion from pancreatic ß-cells and related insulinoma cell lines. We have employed a novel fluorescent plasma membrane potential (Δψ(p)) indicator in combination with indicators of cytoplasmic free Ca(2+) ([Ca(2+)](c)), mitochondrial membrane potential (Δψ(m)), matrix ATP concentration, and NAD(P)H fluorescence to investigate the role of mitochondria in the generation of plasma membrane potential oscillations in clonal INS-1 832/13 ß-cells. Elevated glucose caused oscillations in plasma membrane potential and cytoplasmic free Ca(2+) concentration over the same concentration range required for insulin release, although considerable cell-to-cell heterogeneity was observed. Exogenous pyruvate was as effective as glucose in inducing oscillations, both in the presence and absence of 2.8 mM glucose. Increased glucose and pyruvate each produced a concentration-dependent mitochondrial hyperpolarization. The causal relationships between pairs of parameters (Δψ(p) and [Ca(2+)](c), Δψ(p) and NAD(P)H, matrix ATP and [Ca(2+)](c), and Δψ(m) and [Ca(2+)](c)) were investigated at single cell level. It is concluded that, in these ß-cells, depolarizing oscillations in Δψ(p) are not initiated by mitochondrial bioenergetic changes. Instead, regardless of substrate, it appears that the mitochondria may simply be required to exceed a critical bioenergetic threshold to allow release of insulin. Once this threshold is exceeded, an autonomous Δψ(p) oscillatory mechanism is initiated.

Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment.

OBJECTIVE: To determine the safety and efficacy of rituximab treatment in patients with active seropositive rheumatoid arthritis (RA) who had experienced an inadequate response to treatment with anti-tumor necrosis factor-alpha agents and/or traditional disease modifying antirheumatic drugs. METHODS: Rituximab was administered to 17 patients as weekly infusions for 4 consecutive weeks. Patients continued their baseline therapy and were followed for 28 weeks. RESULTS: All patients were evaluable for safety, and 13 for efficacy. Profound B cell depletion occurred by 12 weeks and was sustained at 24 weeks, whereas T cell, complement, and immunoglobulin levels remained within normal ranges. Rituximab was well tolerated, with no infusion related reactions and only mild/moderate adverse events. American College of Rheumatology 20% response (ACR20) was achieved in 55% of patients by Week 5, 75% by Week 8, 50% at Week 16, and 67% at Week 28. Corresponding ACR50 and ACR70 responses were achieved in 36% and 18%, 25% and 17%, 42% and 25%, and 33% and 17% of patients at Weeks 5, 8, 16, and 28, respectively. There were significant improvements over baseline in tender and swollen joint counts (p < 0.0001), physician's global assessment of disease activity (p = 0.0001), and patient assessed pain (p = 0.0005) and disability (p = 0.0386). Erythrocyte sedimentation rate (p = 0.0361) and rheumatoid factor titers (p < 0.0001) also decreased significantly. CONCLUSION: These results support the hypothesis that B cells play an important role in RA pathophysiology, and suggest that rituximab is effective and well tolerated, with a rapid onset of clinical benefit, in patients with refractory, seropositive active RA.