Protocolized screening and detection of occult alcohol use before and after liver transplant: Lessons learned from a quality improvement initiative.

INTRODUCTION: Detection of alcohol (ETOH) use with biomarkers provides an opportunity to intervene and treat patients with alcohol use disorder before and after liver transplant (LT). We describe our center's experience using urine ethyl glucuronide (EtG) and serum phosphatidylethanol (PEth) in alcohol screening protocols. METHODS: Single-center, retrospective review of patients presenting for LT evaluation, patients waitlisted for LT for alcohol-associated liver disease (ALD), and patients who received a LT for ALD over a 12-month period, from October 1, 2019 through September 30, 2020. Patients were followed from waitlisting to LT, or for up to 12 months post-LT. We monitored protocol adherence to screening for ETOH use- defined as completion of all possible tests over the follow-up period- at the initial LT visit, while on the LT waitlist and after LT. RESULTS: During the study period, 227 patients were evaluated for LT (median age 57 years, 58% male, 78% white, 54.2% ALD). Thirty-one patients with ALD were placed on the waitlist, and 38 patients underwent LT for ALD during this time period. Protocolized adherence to screening for alcohol use was higher for PEth for all LT evaluation patients (191 [84.1%] vs. 146 [67%] eligible patients, p < .001), in patients with ALD waitlisted for LT (22 [71%] vs. 14 (48%] eligible patients, p = .04) and after LT for ALD, 20 (33 [86.8%] vs. 20 [52.6%] eligible patients, p < .01). Few patients with a positive test in any group completed chemical dependency treatment. CONCLUSIONS: When screening for ETOH use in pre- and post-LT patients, protocol adherence is higher using PEth compared to EtG. While protocolized biomarker screening can detect recurrent ETOH use in this population, engagement of patients into chemical dependency treatment remains challenging.

Dual-graft adult living donor liver transplantation with ABO-incompatible graft: short-term and long-term outcomes.

ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short- and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end-stage liver disease score was 12.2 ± 4.6. The 1-, 3-, and 5-year patient survival rate was 96.4% during the mean follow-up period of 57.0 ± 22.4 months. The 1-, 3-, and 5-year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO-compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.

Successful Renal Transplantation in Small Children With a Completely Thrombosed Inferior Vena Cava.

In small children with end-stage renal disease, an adult-sized kidney transplant is the best option. However, in the face of a completely thrombosed inferior vena cava (IVC), such transplants can be challenging, given the difficulty of achieving adequate renal venous outflow and the risk of graft thrombosis. Using a new technique to anastomose the renal vein to the right hepatic vein/IVC junction, we successfully implanted an adult-sized graft in two small children (9.8 and 14 kg) who had end-stage renal disease and a completely thrombosed IVC. After mobilizing the right lobe of the liver and obtaining total vascular occlusion of the liver, we used a Fogarty catheter to dilate the retrohepatic IVC. In the right hepatic vein, we made a venotomy and extended it inferiorly onto the retrohepatic IVC. To that venotomy, we anastomosed the donor left renal vein, using continuous 7-0 Prolene sutures. Both patients attained excellent renal allograft function: One had a serum creatinine level of 0.30 mg/dL at 6 mo after transplant, and the other had a level of 0.29 mg/dL at 1 year. In these two small children with completely thrombosed IVC, our technique for transplanting an adult-sized kidney provided adequate venous outflow.

Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single-Center Experience.

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70-78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in-hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1- and 5-year patient survival rates were 84.0% and 69.8%, and the 1- and 5-year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.

The evolving microenvironment of the human hepatocyte: Healthy vs. cirrhotic liver vs. isolated cells.

The study of the liver microenvironment and hepatocyte's response to this environment in the setting of healthy liver, cirrhotic liver or cultured primary human hepatocytes (PHHs) addresses key questions for the development of novel liver therapies and predicts relevance of ex vivo PHHs models in liver biology. This study compared quantitative gene and protein expression of the inflammatory profile, oxidative stress response, angiogenesis and homing mechanisms in the biopsies of healthy and cirrhotic human livers and isolated PHHs. These profiles were correlated with the metabolic health of liver and PHHs defined by albumin production. The analysis demonstrated that cirrhotic liver and PHHs exhibited a distinct upregulation of the pro-inflammatory, oxidative stress and homing mechanism markers when compared to normal liver. The upregulation of the oxidative stress markers in PHHs inversely correlated with the albumin production. PHHs had diverse secretion of matrix metalloproteinases and their inhibitors, reflective of the cellular response to non-physiological culture conditions. The current study suggests that ex vivo PHHs manifest adaptive behavior by upregulating stress mechanisms (similar to the cirrhotic liver), downregulating normal metabolic function and upregulating matrix turnover. The ex vivo profile of PHHs may limit their therapeutic functionality and metabolic capacity to serve as in vitro metabolism and toxicology models.

Genetic Traits in the Liver Anatomy Between Parents and Children: An Analysis of Liver Transplant Recipients and Living Donors.

BACKGROUND: To date, no significant similarities in the anatomy of the hepatic vasculature have been observed between blood-related individuals. However, we have frequently encountered anatomic similarities between parents and their children; thus, we performed an analysis of the genetic traits in the anatomy of the liver. METHODS: The study cohort was 330 adult cases of living-donor liver transplantation (LDLT), in which the donor-recipient relationship was child to parent. The subjects underwent LDLT from January 2013 to December 2014. Preoperative dynamic computerized tomographic scans were used to classify the anatomy of the hepatic vasculature. RESULTS: Portal vein (PV) anatomy was classified as typical and 2 variant types. PV anatomy combinations in donor and recipient were typical in 232 subjects, variant in 16, and typical-variant in 82. The PV concordance rate was 75.2%, and the contingency coefficient was 0.130 (P = .017). Hepatic artery (HA) anatomy was classified as typical and 4 variant types. HA anatomy combinations in donor and recipient were typical in 167 subjects, variant in 33, and typical-variant in 130. The HA concordance rate was 60.6%, and the contingency coefficient was 0.058 (P = .294). The sizable inferior right hepatic vein in donor and recipient was present in 44 subjects, absent in 160, and discordant in 126; its concordance rate was 61.8% and contingency coefficient 0.133 (P = .014). CONCLUSIONS: There may be a shared but weak genetic trait between parents and children regarding the anatomy of the PV and inferior hepatic vein. This information may be helpful when LDLT is performed between 1st-degree relatives.

[Anaemia treatment in gynaecology: use of epoetin in onco-gynaecology and gynaecological surgery]. / Traitement de l'anémie en gynécologie: utilisation de l'époétine en onco-gynécotogie et en chirurgie gynécologique.

In gynaecology, anaemia treatment is indicated in extremely different situations. In cancer patients, treatment with epoetin can relieve fatigue and improve quality of life. In these patients, epoetin treatment can also have a positive influence on survival through increasing the efficacy of radiotherapy and chemotherapy. Recent data are presented. In gynaecological surgery, the use of epoetin--based on results in oncology and orthopaedic surgery--makes a constructive contribution to the improvement of quality of life and during patient recovery through rapid normalisation of perioperative anaemia, thus reducing the risk of a transfusion with donated blood. Encouraging data from recent publications concerning the prevention of PRCA under epoetin treatment are presented.

A double-blind crossover study comparing prophylactic intravenous granisetron alone or in combination with dexamethasone as antiemetic treatment in controlling nausea and vomiting associated with chemotherapy.

The efficacies of granisetron plus dexamethasone and granisetron alone in controlling nausea and vomiting during two consecutive cycles of moderately emetogenic chemotherapy given for up to 5 days were compared in a two-centre, randomised, double-blind, placebo-controlled crossover study. In all, 110 evaluable patients received either dexamethasone, 20 mg i.v., or matching placebo, plus open-label granisetron, 3 mg i.v., given on each chemotherapy day. At cycle 2, patients crossed over to the alternative treatment; 72 patients completed the crossover. In these 72 patients, the complete response rates over 24 h for granisetron plus dexamethasone and granisetron plus placebo in cycle 1 were 87% and 70% (ns), respectively. In cycle 2 the complete response rates over 24 h were 73% and 62% (ns). Combining the two cycles, the complete response rates over 24 h were 80.6% (granisetron plus dexamethasone) and 65.3% (granisetron plus placebo; P = 0.015). Granisetron plus dexamethasone was significantly more effective in terms of times to less than complete response (P = 0.041), to first episode of moderate/severe nausea (P = 0.04), to first episode of vomiting (0.03) and to use of rescue medication (P = 0.02). Adverse events tended to be minor, with asthenia and insomnia the most common. Of those patients who expressed a preference, 67% preferred granisetron plus dexamethasone (P < 0.05). A single dose of dexamethasone added to granisetron thus enhances the efficacy of granisetron alone in preventing nausea and vomiting after moderately emetogenic chemotherapy.

Selective serotonin reuptake inhibitors and hyponatraemia: review and proposed mechanisms in the elderly.

The association between selective serotonin reuptake inhibitors (SSRIs) and hyponatraemia has been well documented, the elderly appearing to be at greatest risk. An analysis of data of hyponatraemia in the elderly using SSRIs from all published cases and from the Committee on Safety of Medicines found that the mean time to detection was about 3 weeks after commencing SSRIs. A wide range of time to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is detected by chance rather than being specifically looked for. In the elderly there are physiological changes, a high prevalence of medical illnesses and concomitant drug use, which may precipitate hyponatraemia. Together with a risk of altered water regulation in psychiatric illness this may account for the particular susceptibility of the elderly to hyponatraemia whilst using SSRIs.

Thioridazine for dementia.

BACKGROUND: Neuroleptic drugs are controversial treatments in dementia, with evidence accumulating that they may hasten clinical decline. Despite these concerns, they are commonly prescribed for elderly and demented patients. Thioridazine, a phenothiazine neuroleptic, has been commonly prescribed because it was thought to produce relatively less frequent motor side effects. The drug has significant sedative effect, and it is thought that this is the main mechanism of action in calming and controlling the patient. However, pharmacologically, it also has marked anticholinergic properties that could potentially have a detrimental effect on cognitive function. OBJECTIVES: To evaluate the efficacy of thioridazine in dementia in terms of: 1) efficacy in controlling symptoms 2) cognitive outcome for the patient 3) safety SEARCH STRATEGY: The Cochrane Controlled Trials Register and other electronic databases were searched using the terms 'thioridazine', 'melleril', 'dementia' and 'old age'. In addition, Novartis, the pharmaceutical company that developed and markets thioridazine, was approached and asked to release any published or unpublished data they had on file. SELECTION CRITERIA: Unconfounded, single-blind or double-blind, randomised trials were identified in which treatment with thioridazine was administered for more than one dose and compared to an alternative intervention in patients with dementia of any aetiology. Trials in which allocation to treatment or comparator were not truly random, or in which treatment allocation was not concealed, were reviewed but are not included in the data analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (VK, CAK and RJH). For continuous and ordinal variables, the main outcome measures of interest were the final assessment score and the change in score from baseline to the final assessment. The assessment scores were provided by behavioural rating scales, clinical global impression scales, functional assessment scales, psychometric test scores, and frequency and severity of adverse events. Data were pooled where appropriate or possible, and the Peto odds ratio (95%CI) or the weighted mean difference (95%CI) estimated. Where possible, intention to treat data were used. MAIN RESULTS: The meta-analysis showed that, compared with placebo, thioridazine reduced anxiety symptoms as evidenced by changes on the Hamilton Anxiety Scale. However, there was no significant effect on clinical global change, and a non-significant trend for higher adverse effects with thioridazine. Compared to diazepam, thioridazine was superior in terms of some anxiety symptoms, with similar adverse effects. Global clinical evaluation scales did not favour either treatment. Compared to chlormethiazole, thioridazine was significantly inferior when assessed on some items of the CAPE and the Crichton Geriatric Behavioural Rating Scales. Thioridazine was also associated with significantly more dizziness. No superiority for thioridazine was shown in comparisons with etoperidone, loxapine or zuclopenthixol, except to produce fewer side effects than loxapine. REVIEWER'S CONCLUSIONS: Very limited data are available to support the use of thioridazine in the treatment of dementia. If thioridazine were not currently in widespread clinical use, there would be inadequate evidence to support its introduction. The only positive effect of thioridazine when compared to placebo is the reduction of anxiety. When compared to placebo, other neuroleptics, and other sedatives, it has equal or higher rates of adverse effects. Clinicians should be aware that there is no evidence to support the use of thioridazine in dementia, and its use may expose patients to excess side effects.

Propentofylline for dementia.

BACKGROUND: Propentofylline is a novel therapeutic agent for dementia that readily crosses the blood-brain barrier and acts by blocking the uptake of adenosine and inhibiting the enzyme phosphodiesterase. In vitro and in vivo its mechanism of action appears to be twofold; it inhibits the production of free radicals and reduces the activation of microglial cells. It therefore interacts with the inflammatory processes that are thought to contribute to dementia, and given its mechanism of action is a possible disease modifying agent rather than a purely symptomatic treatment. OBJECTIVES: To determine the clinical efficacy and safety of propentofylline for people with dementia. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 5 February 2003. Aventis, the manufacturing pharmaceutical company, was asked for data from unpublished studies but declined to enter into correspondence. SELECTION CRITERIA: Unconfounded double-blind randomized controlled trials of propentofylline compared with a placebo or another treatment group. DATA COLLECTION AND ANALYSIS: There were detailed reports of only four of the nine included studies. The efficacy of propentofylline was reviewed for undifferentiated dementia as there were not enough data to attempt a subgroup analysis for the types of dementia. MAIN RESULTS: The following statistically significant treatment effects in favour of propentofylline are reported. Cognition at 3, 6 and 12 months including MMSE at 12 months. [MD 1.2, 95%CI 0.12 to 2.28, P=0.03] Severity of dementia at 3, 6 and 12 months including CGI at 12 months [MD -0.21, 95%CI -0.39 to -0.03, P=0.03]. Activities of Daily Living (NAB) at 6 and 12 months [MD -1.20, 95%CI -2.22 to -0.18, P=0.02]. Global Assessment (CGI) at 3 months [MD -0.48, 95% CI -0.75 to -0.21, P=0.0006], but not at later times. Tolerability There were minimal data on adverse effects and drop-outs. There were a statistically significant treatment effects in favour of placebo at 12 months, for the number of dropouts, [OR=1.43, 95%CI 1.04 to 1.90, P=0.03]. REVIEWER'S CONCLUSIONS: There is limited evidence that propentofylline might benefit cognition, global function and activities of daily living of people with Alzheimer's disease and/or vascular dementia. The meta-analyses reported here are far from satisfactory as a summary of the efficacy of propentofylline, considering the unpublished information on another 1200 patients in randomized trials that exists. Unfortunately Aventis has been unwilling to correspond with the authors, significantly limiting the scope of this review.

Thioridazine for dementia.

BACKGROUND: Neuroleptic drugs are controversial treatments in dementia, with evidence accumulating that they may hasten clinical decline. Despite these concerns, they are commonly prescribed for elderly and demented patients. Thioridazine, a phenothiazine neuroleptic, is one of the most commonly prescribed. It has often been a preferred agent because it is thought to produce relatively less frequent motor side effects. The drug has significant sedative effects, and it is thought that these are the main mechanism of action in calming and controlling the patient. However, pharmacologically, it also has marked anticholinergic properties that could potentially have a detrimental effect on cognitive function. OBJECTIVES: To determine the evidence on which the use of thioridazine in dementia is based in terms of: 1) efficacy in controlling symptoms 2) cognitive outcome for the patient 3) safety SEARCH STRATEGY: The Cochrane Controlled Trials Register and other electronic databases were searched using the terms 'thioridazine', 'melleril', 'dementia' and 'old age'. In addition, Novartis, the pharmaceutical company that developed and markets thioridazine, was approached and asked to release any published or unpublished data they had on file. SELECTION CRITERIA: Unconfounded, single-blind or double-blind, randomised trials were identified in which treatment with thioridazine was administered for more than one dose and compared to an alternative intervention in patients with dementia of any aetiology. Trials in which allocation to treatment or comparator were not truly random, or in which treatment allocation was not concealed were reviewed but are not included in the data analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (VC, CAK and RJH). For continuous and ordinal variables, the main outcome measures of interest were the final assessment score and the change in score from baseline to the final assessment. The assessment scores were provided by behavioural rating scales, clinical global impression scales, functional assessment scales, psychometric test scores, and frequency and severity of adverse events. Data were pooled where appropriate or possible, and the Peto odds ratio (95%CI) or the weighted mean difference (95%CI) estimated. Where possible, intention to treat data were used. MAIN RESULTS: The meta-analysis showed that, compared with placebo, thioridazine reduced anxiety symptoms as evidenced by changes on the Hamilton Anxiety Scale. However, there was no significant effect on clinical global change, and a non-significant trend for higher adverse effects with thioridazine. Compared to diazepam, thioridazine was superior in terms of some anxiety symptoms, with similar adverse effects. Global clinical evaluation scales mostly did not favour either treatment. Compared to chlormethiazole, thioridazine was significantly inferior when assessed on some items of the CAPE and the Crichton Geriatric Behavioural Rating Scales. Thioridazine was also associated with significantly more dizziness. No superiority for thioridazine was shown in comparisons with etoperidone, loxapine or zuclopenthixol. REVIEWER'S CONCLUSIONS: Very limited data are available to support the use of thioridazine in the treatment of dementia. If thioridazine were not currently in widespread clinical use, there would be inadequate evidence to support its introduction. The only positive effect of thioridazine when compared to placebo is the reduction of anxiety. When compared to placebo, other neuroleptics, and other sedatives it has equal or higher rates of adverse effects. Clinicians should be aware that there is no evidence to support the use of thioridazine in dementia, and its use may expose patients to excess side effects.

Enteric parasites in east African immigrants. Symptoms and duration of U.S. residence are not predictive.

The Minnesota Department of Health recommends a health assessment for all refugees within 1 to 3 months of arrival, including screening for enteric parasites. Little information exists, however, to help clinicians decide whether to screen asymptomatic persons who have lived in the United States for a year or more. We questioned 71 immigrants from East Africa now living in Minnesota's Twin Cities about gastrointestinal symptoms and duration of residence in the United States and asked for stool specimens for ova and parasite examination. Fifty-one patients (72%) returned specimens. The prevalence of symptoms was no different in the 14 patients with pathogenic parasites than in the 37 without (71% vs. 76%). Patients with pathogens were likely to have lived in the United States for less time than those without pathogens (median 17 months vs. 32 months), but the groups were not discrete. Clinical data did not identify a group unlikely to have parasites or need screening.

Anti-CD25 antibody (daclizumab) maintenance therapy in pancreas transplantation.

BACKGROUND: Calcineurin inhibitors (CNI) are the basis of contemporary immunosuppression in clinical pancreas transplantation (PT). Nevertheless, CNI toxicities, especially nephrotoxicity, have stimulated the search for CNI-sparing protocols. We performed a retrospective analysis of 25 PT patients with progressive CNI toxicities that were switched to a daclizumab (DAC)-based maintenance regimen. METHODS: From 2003 to 2007, 25 PT patients with progressive CNI toxicity (predominantly nephrotoxicity) were identified and switched from CNI to monthly DAC maintenance therapy. The DAC group was compared with matched control subjects (1:1) by transplant type and number, age, year of transplant, and duct management. RESULTS AND CONCLUSIONS: Results showed improved graft survival rates and decreased immunologic loss rates at 1, 3, and 5 years in the DAC group compared with the control group. There was no difference in patient survival rate between the 2 groups. Analysis demonstrates that DAC maintenance therapy is safe and effective for PT patients experiencing CNI toxicities. A randomized trial to compare DAC- and CNI-based regimens is needed in CNI-intolerant patients, with particular attention to the impact on renal function and patient morbidity (eg, infection rates).

Continuous real-time viability assessment of kidneys based on oxygen consumption.

BACKGROUND: Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation. METHODS: Five porcine kidneys were procured using a donation after cardiac death (DCD) model. The renal artery and renal vein were cannulated and the kidney connected to a custom-made hypothermic machine perfusion (HMP) system equipped with an inline oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8 degrees C, and the perfusion parameters and partial oxygen pressures (pO(2)) were measured to calculate WOOCR. RESULTS: Without an inline oxygenator, the pO(2) of the perfusion solution at the arterial inlet and venous outlet diminished to near 0 within minutes. However, once adequate oxygenation was provided, a significant pO(2) difference was observed and used to calculate the WOOCR. The WOOCR was consistently measured from presumably healthy kidneys, and results suggest that it can be used to differentiate between healthy and purposely damaged organs. CONCLUSIONS: Custom-made HMP systems equipped with an oxygenator and inline oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a promising approach for the real-time quality assessment of kidneys and other organs during preservation before transplantation.

Surgical protocol involving the infusion of paramagnetic microparticles for preferential incorporation within porcine islets.

INTRODUCTION: Despite significant advances, widespread applicability of islet cell transplantation remains elusive. Refinement of current islet isolation protocols may improve transplant outcomes. Islet purification by magnetic separation has shown early promise. However, surgical protocols must be optimized to maximize the incorporation of paramagnetic microparticles (MP) within a greater number of islets. This study explores the impact of MP concentration and infusion method on optimizing MP incorporation within islets. METHODS: Five porcine pancreata were procured from donors after cardiac death. Splenic lobes were isolated and infused with varying concentrations of MP (8, 16, and 32 × 10(8) MP/L of cold preservation solution) and using one of two delivery techniques (hanging bag versus hand-syringe). After procurement and infusion, pancreata were stored at 0°C to 4°C during transportation (less than 1 hour), fixed in 10% buffered formalin, and examined by standard magnetic resonance imaging (MRI) and histopathology. RESULTS: T2*-weighted MRI showed homogeneous distribution of MP in all experimental splenic lobes. In addition, histologic analysis confirmed that MP were primarily located within the microvasculature of islets (82% to 85%), with few MP present in acinar tissue (15% to 18%), with an average of five to seven MP per islet (within a 5-µm thick section). The highest MP incorporation was achieved at a concentration of 16 × 10(8) MP/L using the hand-syringe technique. CONCLUSION: This preliminary study suggests that optimization of a surgical protocol, MP concentrations, and applied infusion pressures may enable more uniform distribution of MP in the porcine pancreas and better control of MP incorporation within islets. These results may have implications in maximizing the efficacy of islet purification by magnetic separation.

Pancreas oxygen persufflation increases ATP levels as shown by nuclear magnetic resonance.

BACKGROUND: Islet transplantation is a promising treatment for type 1 diabetes. Due to a shortage of suitable human pancreata, high cost, and the large dose of islets presently required for long-term diabetes reversal; it is important to maximize viable islet yield. Traditional methods of pancreas preservation have been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen delivery is a key area of improvement. In this paper, we explored improved oxygen delivery by persufflation (PSF), ie, vascular gas perfusion. METHODS: Human pancreata were obtained from brain-dead donors. Porcine pancreata were procured by en bloc viscerectomy from heparinized donation after cardiac death donors and were either preserved by either two-layer method (TLM) or PSF. Following procurement, organs were transported to a 1.5-T magnetic resonance (MR) system for (31)P nuclear magnetic resonance spectroscopy to investigate their bioenergetic status by measuring the ratio of adenosine triphosphate to inorganic phosphate (ATP:P(i)) and for assessing PSF homogeneity by MRI. RESULTS: Human and porcine pancreata can be effectively preserved by PSF. MRI showed that pancreatic tissue was homogeneously filled with gas. TLM can effectively raise ATP:P(i) levels in rat pancreata but not in larger porcine pancreata. ATP:P(i) levels were almost undetectable in porcine organs preserved with TLM. When human or porcine organs were preserved by PSF, ATP:P(i) was elevated to levels similar to those observed in rat pancreata. CONCLUSION: The methods developed for human and porcine pancreas PSF homogeneously deliver oxygen throughout the organ. This elevates ATP levels during preservation and may improve islet isolation outcomes while enabling the use of marginal donors, thus expanding the usable donor pool.

Persufflation improves pancreas preservation when compared with the two-layer method.

Islet transplantation is emerging as a promising treatment for patients with type 1 diabetes. It is important to maximize viable islet yield for each organ due to scarcity of suitable human donor pancreata, high cost, and the large dose of islets required for insulin independence. However, organ transport for 8 hours using the two-layer method (TLM) frequently results in low islet yields. Since efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has recently come under question, we investigated oxygen persufflation as an alternative way to supply the pancreas with oxygen during preservation. Porcine pancreata were procured from donors after cardiac death and preserved by either TLM or persufflation for 24 hours and subsequently fixed. Biopsies collected from several regions of the pancreas were sectioned, stained with hematoxylin and eosin, and evaluated by a histologist. Persufflated tissues exhibited distended capillaries and significantly less autolysis/cell death relative to regions not exposed to persufflation or to tissues preserved with TLM. The histology presented here suggests that after 24 hours of preservation, persufflation dramatically improves tissue health when compared with TLM. These results indicate the potential for persufflation to improve viable islet yields and extend the duration of preservation, allowing more donor organs to be utilized.

'It's like a revolving door syndrome': professional perspectives on models of access to services for people with early-stage dementia.

As the need for services for people with dementia grows, and the benefits of early intervention become clear, it has become important to understand what factors may improve access to services for people with early-stage dementia. There are a number of models of service access, and these emphasise different areas, whether individual factors, relationships, or social context. The relevance of these models to variations in service access for people with early-stage dementia, and how well they relate to professional accounts, is not well known. In this study, 30 key professionals were interviewed about access to services for people with early-stage dementia in order to explore how different models of access were reflected in their own understandings. People with early-stage dementia were thought to have a range of complex needs, but participants felt these needs remained largely unmet. When articulating the reasons why they thought needs were unmet, participants focused on the impact of the framework within which services are delivered. The findings highlight the importance of considering relationships and socio-contextual factors, such as the impact of the framework of service delivery, when attempting to understand variations in access to services. In order to improve access to services, it will be necessary to move beyond addressing individual factors relating to access, and to consider the impact of the framework for service delivery and the relationships that influence contact with services.

Clinical studies to assess the economic impact of new therapies: pragmatic approaches to measuring costs.

Pragmatic clinical trials using unselected patients in normal clinical situations are more appropriate for the economic assessment of new drugs. However, standard clinical studies that do not reflect current practice are useful and at present the only source of information. Anti-emetic drug studies using granisetron and ondansetron have demonstrated that the overall economic impact of these drugs is equivalent to standard therapies such as metoclopramide. Thus, an efficient anti-emetic drug with less frequent dosing, using a simplified dosage regimen and producing a reduction in anticipatory nausea and vomiting and in nursing time, may result in an overall reduction in cost. Decisions made purely on the basis of drug costs may be misleading and promote inefficient use of health resources.