Development of Donor Yield Models Messersmith, E. E.; Arrington, C.; Alexander, C. ...
American journal of transplantation,
October 2011, Letnik:
11, Številka:
10
Journal Article
Recenzirano
Increasing donor yield, or the number of organs transplanted per donor, has been a focus of the transplant community in recent years. However, an exclusive focus on observed yield, unadjusted for the ...donor characteristics, ignores important differences between donors and donor case mixes in donation service areas (DSAs). We analyzed deceased donor registry data from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients from January 2006 to December 2009 (N = 32 116 donors). Overall yields and kidney yields were modeled using ordinal logistic regression, and logistic regression was used to model heart, lung, pancreas and liver yields. Donor characteristics, including demographics, historical information and positive serology were related to overall and organ‐specific yield. This study shows the potential value of the yield models as evaluation metrics and as tools that can inform DSA‐wide practices in donor management and can improve organ utilization.
This study shows the potential value of models predicting organ yield per donor as evaluation metrics and tools that can inform practices in donor management and organ utilization. See editorial by Goldfarb and Schold on page 2009.
Abstract Background An organ procurement organization (OPO) and a level I trauma center developed catastrophic brain injury guidelines (CBIGs) to assist in the care of severely brain-injured adult ...patients before brain death. The CBIGs provided a set of clinical guidelines to maintain patient stability and optimize opportunity for organ donation. Objective The aim of this study was to determine if the use of the CBIGs affected the OPO's ability to achieve donor management goals (DMGs) before organ recovery. Methods We conducted a retrospective analysis comparing the number of DMGs met in the hospital's donors before and after the CBIGs were used. The analysis included 133 cases; 67 donors in the pre-CBIG data and 66 donors in the post-CBIG review. Donor management goals measured included: systolic blood pressure >100 mm Hg; 1 pressor ≤10 μg/kg/min; urine output 1–2 mL/kg/h; pO2 >100 mm Hg; Na <160 meq/L; pH within normal limits (7.35–7.45); temperature 36.5–37.5°C; arterial line in place and central line in place with monitor. Results After the introduction of the CBIGs, 78% of DMGs were met more often, with 1 goal (Na) remaining equivalent and 2 goals (pO2 and pH) met less often. Increase in achievement of individual DMGs ranged from 4% to 33%. The pre-CBIG cases averaged 2.90 missed goals per donor compared with an average of 1.79 in the post-CBIG data. Only 5 pre-CBIG donors (7%) achieved all of the DMGs. That figure rose to 12 donors (18%) in the post-CBIG data. Conclusions While other factors may have contributed to our results, we think that there is a positive relationship between the CBIGs and the increase in meeting most DMGs. As we refine our donor management, we will focus on the factors we met less successfully. Ultimately, the use of the CBIGs before brain death led to more stable donors, maximizing transplantable organs.
Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration ...and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (T
cells). Most of the patients demonstrated an immunological response to pembrolizumab. Clinical failure in many patients was not solely due to an inability to induce immune reinvigoration, but rather resulted from an imbalance between T-cell reinvigoration and tumour burden. The magnitude of reinvigoration of circulating T
cells determined in relation to pretreatment tumour burden correlated with clinical response. By focused profiling of a mechanistically relevant circulating T-cell subpopulation calibrated to pretreatment disease burden, we identify a clinically accessible potential on-treatment predictor of response to PD-1 blockade.
Immunologic responses to anti-PD-1 therapy in melanoma patients occur rapidly with pharmacodynamic T cell responses detectable in blood by 3 weeks. It is unclear, however, whether these early ...blood-based observations translate to the tumor microenvironment. We conducted a study of neoadjuvant/adjuvant anti-PD-1 therapy in stage III/IV melanoma. We hypothesized that immune reinvigoration in the tumor would be detectable at 3 weeks and that this response would correlate with disease-free survival. We identified a rapid and potent anti-tumor response, with 8 of 27 patients experiencing a complete or major pathological response after a single dose of anti-PD-1, all of whom remain disease free. These rapid pathologic and clinical responses were associated with accumulation of exhausted CD8 T cells in the tumor at 3 weeks, with reinvigoration in the blood observed as early as 1 week. Transcriptional analysis demonstrated a pretreatment immune signature (neoadjuvant response signature) that was associated with clinical benefit. In contrast, patients with disease recurrence displayed mechanisms of resistance including immune suppression, mutational escape, and/or tumor evolution. Neoadjuvant anti-PD-1 treatment is effective in high-risk resectable stage III/IV melanoma. Pathological response and immunological analyses after a single neoadjuvant dose can be used to predict clinical outcome and to dissect underlying mechanisms in checkpoint blockade.
The first cases of West Nile virus (WNV) transmitted through solid organ transplantation (SOT) were identified in 2002. Subsequently, 5 additional clusters have been reported to public health ...officials in the United States. Based upon a limited number of known cases, patients who acquire WNV from infected donor organs might be at higher risk for severe neurologic disease and death, compared with patients infected through mosquito bites. In response, some organ procurement organizations (OPOs) have instituted pre‐transplant screening of organ donors for WNV infection. We evaluated the current practices, concerns, and challenges related to screening organ donors for WNV in the United States by reviewing the relevant medical literature and interviewing key stakeholders. Screening organ donors for WNV is not required by national policy. In 2008, 11 (19%) of 58 OPOs performed WNV screening using nucleic acid amplification testing (NAT). These OPOs differ in their screening strategies, NAT performed, and logistical challenges. Concerns of delays in receiving NAT results before transplant and potential false‐positive results leading to organ wasting are limitations to more widespread screening. Furthermore, it is unknown if WNV screening practices decrease SOT‐related morbidity and mortality, or if screening is cost‐effective. Additional data are needed to assess and improve transplant outcomes related to WNV.
Continued progress in organ donation will help enable transplantation to alleviate the increasing incidence of end‐stage organ disease. This article discusses the implementation and effect of the ...federally initiated Organ Donation Breakthrough Collaborative; it then reviews organ donation data, living and deceased, from 1995 to 2004. It is the first annual report of the Scientific Registry of Transplant Recipients to include national data following initiation of the collaborative in 2003. Prior to that, annual growth in deceased donation was 2%–4%; in 2004, after initiation of the collaborative, deceased donation increased 11%. Identification and dissemination of best practices for organ donation have emphasized new strategies for improved consent, including revised approaches to minority participation, timing of requests and team design. The number of organs recovered from donation after cardiac death (DCD) grew from 64 in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for identifying expanded criteria donors (ECD) for organs other than kidney, it is clear DCD and ECD raise questions regarding cost and recovery. The number of living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends toward more living unrelated donors and those providing non‐directed donations.
We examined the impact on physician prescribing patterns of pharmaceutical firms offering all-expenses-paid trips to popular
sunbelt vacation sites to attend symposia sponsored by a pharmaceutical ...company. The impact was assessed by tracking the pharmacy
inventory usage reports for two drugs before and after the symposia. Both drugs were available only as intravenous preparations
and could be used only on hospitalized patients. The usage patterns were tracked for 22 months preceding each symposium and
for 17 months after each symposium. Ten physicians invited to each symposium were interviewed about the likelihood that such
an enticement would affect their prescribing patterns. A significant increase in the prescribing pattern of both drugs occurred
following the symposia. The usage of drug A increased from a mean of 81 +/- 44 units before the symposium to a mean of 272
+/- 117 after the symposium (p less than 0.001). The usage of drug B changed from 34 +/- 30 units before the symposium to
87 +/- 24 units (p less than 0.001) after the symposium. These changed prescribing patterns were also significantly different
from the national usage patterns of the two drugs by hospitals with more than 500 beds and major medical centers over the
same period of time. These alterations in prescribing patterns occurred even though the majority of physicians who attended
the symposia believed that such enticements would not alter their prescribing patterns.
Cleveland Clinic Foundation
Empirical Approach
Health Care and Public Health
Professional Patient Relationship
Summary
The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the ...immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, but also in maintaining long‐term disease control, has been unprecedented. While the foundation for this approach has been firmly set in place, continued development will improve the efficacy, toxicity and applicability to other malignancies of this new class of ‘living drugs’. In this review, we provide a comprehensive overview of the most current clinical trial data in both acute and chronic leukaemias, and discuss some of the potential ways to enhance the activity and safety of CART therapy going forward.
Reye's syndrome (RS) appeared suddenly in the 1950s and disappeared almost as quickly in the late 1980s. A number of metabolic disorders were discovered in the 1980s that could completely mimic RS. ...This study was undertaken to reassess the original diagnosis of RS in light of newly described metabolic disorders.
The medical records of 26 patients who had survived RS and were originally studied in Australia in the 1980s were reexamined 10 yrs later, and families were interviewed to ascertain if the diagnosis had changed. The 49 original patients with RS from Australia were also reanalyzed using more precise diagnostic criteria for RS to ascertain how many of the patients would continue to fit the more precise diagnosis of RS.
Of 26 original patients with RS who had survived, 18 (69%) were subsequently diagnosed as having other diseases, most commonly inborn errors of metabolism. The most commonly diagnosed metabolic disorder was medium-chain acyl-coenzyme-A dehydrogenase deficiency. Of the 18 patients rediagnosed with diseases other than RS, 15 (83%) are now known to have metabolic disorders. By using more precise diagnostic criteria for RS, none of the original 49 patients with RS could be diagnosed as having certain RS. Only six patients had probable RS, two patients had possible RS, 23 patients had unlikely RS, and 18 patients were excluded as RS cases.
With better diagnostic techniques and criteria, most patients originally diagnosed with RS are now known to have metabolic disorders. The disappearance of RS was probably related to the discovery and ability to diagnose inborn errors of metabolism that mimicked RS clinically, biochemically, and pathologically.
Four distinct isoforms of the mammalian Na+/H+ exchanger (NHE) have been identified by molecular cloning. Three of these (NHE-1,
NHE-2, and NHE-3) have been shown to be functionally active by ...heterologous expression. Their kinetic and pharmacological
properties are well documented, yet comparatively little is known about their regulation. In this report, rat NHE-1, NHE-2,
and NHE-3 were stably transfected into antiporter-deficient Chinese hamster ovary cells to study their role in cellular proliferation
and their regulation by nucleotides and cell volume. Their ability to influence cell proliferation was assessed by measuring
the growth of antiporter-deficient cells and of the different transfectants in media of varying pH. While antiporter-deficient
cells were unable to grow at acidic pH levels, all three isoforms supported proliferation under these conditions. Therefore,
while the epithelia-specific isoforms (NHE-2 and NHE-3) are thought to play primarily a role in transcellular ion transport,
they can also contribute to intracellular pH (pHi) homeostasis and have a permissive role in cell growth. The activity of
the three isoforms was markedly inhibited by depletion of cellular ATP. In the pHi 6.0-7.2 range, decreases in the affinity
for internal H+ and/or the maximal rate of transport accounted for the inhibitory effect, depending on the isoform. The osmotic
responsiveness of the three isoforms was also compared. As reported earlier, NHE-1 was stimulated by hypertonicity. Under
similar conditions, NHE-2 was also stimulated to a comparable extent. Conversely, both isoforms were inhibited in hypotonic
media. In contrast, NHE-3 was markedly inhibited by hypertonic cell shrinking but was unaffected by hypotonicity. Osmotic
inhibition of NHE-3 was rapid, reversible, and apparent throughout the pH range studied. Osmotic inhibition of NHE-3 may play
a role in the physiology and pathophysiology of epithelia.
PDF
