Intensity warping for multisite MRI harmonization.

In multisite neuroimaging studies there is often unwanted technical variation across scanners and sites. These "scanner effects" can hinder detection of biological features of interest, produce inconsistent results, and lead to spurious associations. We propose mica (multisite image harmonization by cumulative distribution function alignment), a tool to harmonize images taken on different scanners by identifying and removing within-subject scanner effects. Our goals in the present study were to (1) establish a method that removes scanner effects by leveraging multiple scans collected on the same subject, and, building on this, (2) develop a technique to quantify scanner effects in large multisite studies so these can be reduced as a preprocessing step. We illustrate scanner effects in a brain MRI study in which the same subject was measured twice on seven scanners, and assess our method's performance in a second study in which ten subjects were scanned on two machines. We found that unharmonized images were highly variable across site and scanner type, and our method effectively removed this variability by aligning intensity distributions. We further studied the ability to predict image harmonization results for a scan taken on an existing subject at a new site using cross-validation.

Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum.

Psychosis commonly develops in adolescence or early adulthood. Youths at clinical high risk (CHR) for psychosis exhibit similar, subtle symptoms to those with schizophrenia (SZ). Malfunctioning neurotransmitter systems, such as glutamate, are implicated in the disease progression of psychosis. Yet, in vivo imaging techniques for measuring glutamate across the cortex are limited. Here, we use a novel 7 Tesla MRI glutamate imaging technique (GluCEST) to estimate changes in glutamate levels across cortical and subcortical regions in young healthy individuals and ones on the psychosis spectrum. Individuals on the psychosis spectrum (PS; n=19) and healthy young individuals (HC; n=17) underwent MRI imaging at 3 and 7 T. At 7 T, a single slice GluCEST technique was used to estimate in vivo glutamate. GluCEST contrast was compared within and across the subcortex, frontal, parietal and occipital lobes. Subcortical (χ2 (1)=4.65, P=0.031) and lobular (χ2 (1)=5.17, P=0.023) GluCEST contrast levels were lower in PS compared with HC. Abnormal GluCEST contrast levels were evident in both CHR (n=14) and SZ (n=5) subjects, and correlated differentially, across regions, with clinical symptoms. Our findings describe a pattern of abnormal brain neurochemistry early in the course of psychosis. Specifically, CHR and young SZ exhibit diffuse abnormalities in GluCEST contrast attributable to a major contribution from glutamate. We suggest that neurochemical profiles of GluCEST contrast across cortex and subcortex may be considered markers of early psychosis. GluCEST methodology thus shows promise to further elucidate the progression of the psychosis disease state.

Unusual shunt for symptomatic portal vein thrombosis after liver transplantation - Clatworthy revisited.

PV thrombosis is not an uncommon occurrence following pediatric LT. Symptomatic PHT following PV thrombosis is treated medically, surgical portosystemic shunting (mesorex, splenorenal, and mesocaval) being reserved for refractory cases. A 10-yr-old boy suffered recurrent malena and hemorrhagic shock because of chronic PV thrombosis following LT nine yr ago (1999). Extensive work-up failed to localize the bleeding source. The liver function remained normal. Initial attempts at surgical shunts failed owing to thrombosis (mesocaval 2001, splenorenal, inferior mesenteric-left renal vein, splenic-left external iliac vein 2008). In this situation, we performed a Clatworthy shunt by anastomosing the divided lower end of the LCIV to the side of SMV. There was a single, large caliber anastomosis. Post-operatively, the malena stopped completely, and clinically, there was no lower limb edema or encephalopathy. Doppler USG revealed persistence of hepatopetal flow within the portal collaterals. Follow-up at two yr reveals stable hepatic function with a patent shunt. To the best of our knowledge, we are not aware of a Clatworthy shunt being performed in a transplant setting. We reviewed the literature pertaining to this shunt in non-transplant patients with PHT.

Porta hepatis in relation to portal vein among Indians.

The porta hepatis / hilum of liver is a transverse fissure located in the inferior surface, where the major vessels and ducts enter or leave the organ. The major structures traversing the porta hepatis are the portal vein, the hepatic artery and the hepatic duct. Porta hepatis is an area of surgical and radiological significance. The knowledge of variations in structures traversing the porta hepatitis will reduce the risk of surgeries involving this area. Study was conducted in the department of anatomy dissection lab after obtaining ethical clearance. 30 liver specimens were used for these studies which were removed from the cadaver during under graduate teaching. Anatomical knowledge of variations in relations of structures present in porta hepatis is of immense help to surgeons and radiologists when they engage patients for clinical procedures like liver transplant, cholecystectomy and diagnostic procedures. Hence this study was aimed to observe the relations of portal vein in porta hepatis.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Complex abdominal wall hernia repair with biologic mesh in elderly: a propensity matched analysis.

BACKGROUND: Complex abdominal wall reconstruction (CAWR) has become a common surgical procedure both in non-elderly and elderly patients. OBJECTIVE: The aim of this study is to analyze the outcomes of the elderly compared to nonelderly undergoing CAWR using propensity score matching. METHODS: All patients who underwent CAWR using porcine-derived, non-crosslinked acellular dermal matrix (ADM) (Strattice™) between January 2014 and July 2017 were studied retrospectively. Propensity matched analysis was performed for risk adjustment in multivariable analysis and for one-to-one matching. The outcomes were analyzed for differences in postoperative complications, reoperations, mortality, hospital length of stay and adverse discharge disposition. RESULTS: One hundred-thirty-six patients were identified during the study period. Non-elderly (aged 18-64 years) constituted 70% (n = 95) and elderly (aged ≥ 65 years) comprised 30% of the overall patient population (n = 41). Seventy-three (56.7%) were females. After adjustment through the propensity score, which included 35 pairs, the surgical site infection (p = 1.000), wound necrosis (p = 1.000), the need for mechanical ventilation (p = 0.259), mortality (p = 0.083), reoperation rate (p = 0.141), hospital length of stay (p = 0.206), and discharge disposition (p = 0.795) were similar. CONCLUSION: Elderly patients undergoing CAWR with biological mesh have comparable outcomes with non-elderly patients when using propensity matching score.

A novel tool to evaluate bias in literature on use of biologic mesh in abdominal wall hernia repair.

PURPOSE: Biologic meshes are being increasingly used for abdominal hernia repair in high-risk patients or patients with a previous history of wound infection, due to their infection-resistant properties. Several studies have been carried out to assess whether biologic mesh is superior to synthetic mesh, as well as to establish guidelines for their use. Unfortunately, most of these studies were not rigorously designed and were vulnerable to different types of bias. The systematic reviews that have been published so far on this topic contain the same biases and limitations of the primary articles that are analyzed. The lack of a literature review on the bias on the use of biological mesh prompted us to conduct the literature search, assessment and plan this article. METHODS: We performed a literature search in PubMed, Embase and Cochrane databases of systematic reviews on biologic mesh for ventral hernia repair. The literature review was conducted using the Population, Intervention, Comparisons, Outcomes and Design approach. We identified 40 studies that matched the stringent criteria we had set. We then created a 13-point instrument to assess for bias and applied it on the primary studies that we intended to analyze. RESULTS: Most primary studies are case series or case reports of patients undergoing abdominal hernia repair with biologic mesh, without any comparison group, and the inclusion of cases was only specified to be consecutive in 6 out of 40 cases. In terms of assessing outcomes, in none of the 40 articles were the outcome assessors blinded to the intervention or exposure status of participants. CONCLUSION: The instrument that we created could allow to assess the risk of bias in different kind of studies. Our assessment of the studies based on the criteria that we had set up in the instrument clearly identified that further research needs to be done due to the lack of unbiased studies regarding the use of biologic meshes for abdominal hernia repair.

1Alpha,25-dihydroxyvitamin D3 attenuates cyanide-induced neurotoxicity by inhibiting uncoupling protein-2 up-regulation.

1Alpha,25-dihydroxyvitamin D(3) (VD(3)) is a neuroprotectant that can reduce cytotoxicity produced by a variety of toxicants. The mechanism of the neuroprotection was studied in rat primary cortical cells in which Wy14,643, an agonist of peroxisome proliferator activated receptor-alpha (PPARalpha), enhances cyanide (KCN) neurotoxicity. In this cell model, Wy14,643 pretreatment enhanced cyanide-induced cell death, and the increased cell death was linked to up-regulation of uncoupling protein-2 (UCP-2). VD(3) reversed cyanide-induced mitochondrial dysfunction in cells pretreated with Wy14,643, as reflected by restoration of cellular ATP and mitochondrial membrane potential (DeltaPsi(m)). Analysis of cellular state 4 oxygen consumption showed increased mitochondrial uncoupling accompanied by up-regulation of UPC-2. The uncoupling was attenuated by prior treatment with VD(3). The interaction of VD(3) with UCP-2 was attributed to increased expression of IkappaB, an inhibitor of NF-kappaB (transcription factor that regulates UCP-2 expression). The increased IkappaB levels lead to reduced nuclear translocation and DNA binding of nuclear factor-kappaB. The role of oxidative stress in the response was then evaluated. Cotreatment with Wy14,643 and cyanide markedly increased reactive oxygen species generation and decreased reduced glutathione levels. The oxidative stress was blocked by VD(3) pretreatment. It was concluded that VD(3) blocks Wy14,643 enhancement of cyanide neurotoxicity by suppressing the redox-mediated transcriptional up-regulation of UCP-2, resulting in reduced mitochondrial proton leak and stabilization of mitochondrial function.

Effects of Low Dose Vasopressin in Catecholamine Resistant Septic Shock.

BACKGROUND: Septic shock commonly leads to death in critically ill patients. Severe hypotension resistant to conventional catecholamine leads to multiorgan failure. We studied the effectiveness of low dose vasopressin in resistant septic shock. METHODS: Thirty critically ill patients with catecholamine resistant hypotension were included in the study. After adequate fluid resuscitation, infusion of norepinephrine and dobutamine was started. If the patient remained hypotensive, vasopressin was infused at a fixed rate of 0.04 unit/minute for 24 hours. Haemodynamic parameters and mortality rates were recorded. RESULT: There was a significant improvement in systolic and mean arterial pressure within four hours of starting vasopressin. This improvement continued throughout the 24-hour period. In addition, it was possible to withdraw dopamine in all the patients and significantly reduce infusion rates of dobutamine and norepinephrine. No significant complication was noted. CONCLUSION: Low dose vasopressin at the rate of 0.04 unit/minute is an effective vasopressor in adult patients with catecholamine resistant septic shock.

Awake Craniotomy for Tumour Excision.

BACKGROUND: Craniotomy and excision of tumours can produce neurological deficits if the tumour is located close to eloquent areas of the brain. One technique of overcoming this problem is to keep the patient 'awake' during surgery. METHODS: Eight patients with intra cranial space occupying lesions (ICSOL) were operated 'awake', using a combination of skull block with sedation and analgesia. A mixture of 0.125% bupivacaine and 0.5% lignocaine was used for various nerve and field blocks. Midazolam, fentanyl and propofol in titrated doses were used to achieve conscious sedation. RESULT: The procedure was successful in all the patients. They tolerated the procedure well and were able to follow the commands intraoperatively as desired. There were no significant complications. CONCLUSION: Awake craniotomy with skull blocks with sedation and analgesia is a well established procedure. It requires a good rapport between surgeon, anaesthesiologist and the patient.

HIF-1alpha activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death.

Cyanide produces degeneration of the nervous system in which different modes of cell death are activated in the vulnerable brain areas. In brain, the mechanism underlying the cell death is not clear. In this study, an immortalized dopaminergic cell line was used to characterize the cell death signaling cascade activated by cyanide. Cyanide-treated cells exhibited a time- and concentration-dependent apoptosis that was caspase independent. Cyanide induced a rapid surge of intracellular reactive oxygen species (ROS) generation, followed by p38 mitogen-activated protein kinase (MAPK) activation and nuclear accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha). Activation of p38 MAPK and HIF-1alpha accumulation were attenuated by N-acetyl-L-cysteine (antioxidant), catalase (hydrogen peroxide scavenger), or a selective p38 MAPK inhibitor (SB203580). Cyanide activated the hypoxia response element (HRE) promoter, which was also blocked by the antioxidants and SB203580. HRE activation was followed by increased BNIP3 gene transcription, as reflected by elevated BNIP3 mRNA and protein levels. BNIP3 upregulation was reduced by selective RNAi knockdown of HIF-1alpha. Overexpression of BNIP3 produced mitochondrial dysfunction (reduced membrane potential), caspase-independent apoptosis, and sensitization of the cells to cyanide-induced toxicity. Expression of a dominant-negative mutant or RNAi knockdown of BNIP3 protected the cells from cyanide. It was concluded that cyanide activated the HIF-1alpha-mediated pathway of BNIP3 induction through a redox-sensitive process. Increased BNIP3 expression then served as an initiator of mitochondrial-mediated death.

Upregulation of BNIP3 and translocation to mitochondria mediates cyanide-induced apoptosis in cortical cells.

Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a Bcl-2 homology domain 3 (BH3) domain only protein, has been identified as a mitochondrial mediator of hypoxia-induced cell death. Since cyanide produces histotoxic anoxia (chemical hypoxia), the present study was undertaken in primary rat cortical cells to determine involvement of the BNIP3 signaling pathway in cyanide-induced death. Over a 20 h exposure KCN increased BNIP3 expression, followed by a concentration-related apoptotic death. To determine if BNIP3 plays a role in the cell death, expression was either increased with BNIP3 cDNA (BNIP3+) or knocked down with small interfering RNA (RNAi). In BNIP3+ cells, cyanide-induced apoptotic death was markedly enhanced and preceded by reduction of mitochondrial membrane potential (delta psim), release of cytochrome c from mitochondria and elevated caspase 3 and 7 activity. Pretreatment with the pan-caspase inhibitor N-benzyloxycarbonyl-Ala-Asp-fluoromethyl ketone (zVAD-fmk) suppressed BNIP3+-mediated cell death, thus confirming a caspase-dependent apoptosis. On the other hand, BNIP3 knockdown by RNAi or antagonism of BNIP3 by a transmembrane-deleted dominant-negative mutant (BNIP3 delta TM) markedly reduced cell death. Immunohistochemical imaging showed that cyanide stimulated translocation of BNIP3 from cytosol to mitochondria and displacement studies with BNIP3 delta TM showed that integration of BNIP3 into the mitochondrial outer membrane was necessary for the cell death. In BNIP3+ cells, cyclosporin-A, an inhibitor of mitochondrial pore transition, blocked the cyanide-induced reduction of delta psim and decreased the apoptotic death. These results demonstrate in cortical cells that cyanide induces a rapid upregulation of BNIP3 expression, followed by translocation to the mitochondrial outer membrane to reduce delta psim. This was followed by mitochondrial release of cytochrome c to execute a caspase-dependent cell death.

Isolated transverse process fractures: insignificant injury or marker of complex injury pattern?

INTRODUCTION: This study investigates the incidence of isolated transverse process fractures (ITPFx) amongst vertebral fractures in trauma patients, and specific-associated injury patterns present in patients with ITPFx. MATERIALS AND METHODS: A retrospective, 4-year review of our Level 1 Trauma Center registry was performed. Patients with blunt spinal column fractures were identified. Data collected included patient demographics, Injury Severity Score (ISS), type of imaging obtained, and concomitant injuries, including rib and pelvic fractures, liver, spleen, and kidney injury (SOI). RESULTS: Of the 10,186 patients admitted during the study period, 881 (8.6%) suffered blunt thoraco-abdominal trauma resulting in vertebral fractures; 214/881 (24%) had ITPFx. All patients (10,186) underwent dedicated spinal multi-detector CT (MDCT) imaging; 26/214 (12.1%) patients had MRI. In all 26 patients, the MRI confirmed the CT findings. 202/214 (94.4%) had associated injuries: rib and pelvic fractures, 45.5 and 20.2%, respectively, and splenic, liver and kidney injury with an incidence of 13.8, 10.9, and 9.4%, respectively. A higher incidence of rib fractures was associated with ITPFx at the T1-4 levels, whereas ITPFx at the level of L5 were associated with pelvic fractures and SOI. Multiple logistic regression analysis identified T1-4 and L5 fractures as predictors of rib fractures and pelvic fractures independent of ISS, with OR: 2.55 (95% CI: 1.12-5.82) and 6.81 (95% CI: 3.14-14.78), respectively. CONCLUSIONS: Based on the results of this study, we conclude that: (1) the use of MDCT imaging has increased the rate of identification of ITPFx; (2) dedicated spinal MDCT reconstruction and MRI may not be necessary to diagnose isolated thoracic and lumbar ITPFx; and (3) ITPFx of the thoracic spine and lower lumbar spine are markers of associated rib fractures and pelvic ring fractures, respectively, as well as of solid organ injuries.

The impact of measurement of respiratory quotient by indirect calorimetry on the achievement of nitrogen balance in patients with severe traumatic brain injury.

BACKGROUND: This study evaluated the impact of IC on the optimization of nutritional support and the achievement of +NB in patients with TBI. MATERIALS AND METHODS: 27 patients (GCS ≤ 8), treated with a 5-day multimodality monitoring and goal-directed therapy protocol, received enteral nutrition on day 1 followed by IC on days 3 and 5 and assessment of NB on day 7. In the first cohort (n = 11), no adjustment in kcal was made. In the second cohort (n = 16), nutrition was targeted to an RQ of 0.83 by day 3. The first cohort was analyzed with respect to NB status; the second cohort was compared to patients with (-) and +NB of the first cohort. Data (mean ± SD) were analyzed with unpaired t test, and Chi square and Fisher exact tests. RESULTS: 4/11(36 %) patients in the first cohort had +NB. The predicted mortality by TRISS, substrate utilization, and RQ was significantly lower compared to the second cohort. The mortality predicted by the CrasH model did not differ between the two cohorts. A RQ of 0.74 was associated with the preferential use of fat and protein and -NB, whereas a RQ of 0.84 favored utilization of carbohydrates and +NB. All patients whose kcal intake was adjusted based on the RQ on day 3 reached a +NB by day 7. CONCLUSION: An increase in kcal ≥25 % in patients with a RQ < 0.83 on day 3 improves substrate utilization, decreases protein utilization and optimizes the achievement of +NB by day 7.

Anterior urethral valves.

We studied the clinical presentation and management of four patients with anterior urethral valves; a rare cause of urethral obstruction in male children. One patient presented antenatally with oligohydramnios, bilateral hydronephrosis and bladder thickening suggestive of an infravesical obstruction. Two other patients presented postnatally at 1 and 2 years of age, respectively, with poor stream of urine since birth. The fourth patient presented at 9 years with frequency and dysuria. Diagnosis was established on either micturating cystourethrogram (MCU) (in 2) or on cystoscopy (in 2). All patients had cystoscopic ablation of the valves. One patient developed a postablation stricture that was resected with an end-to-end urethroplasty. He had an associated bilateral vesicoureteric junction (VUJ) obstruction for which a bilateral ureteric reimplantation was done at the same time. On long-term follow-up, all patients demonstrated a good stream of urine. The renal function is normal. Patients are continent and free of urinary infections. Anterior urethral valves are rare obstructive lesions in male children. The degree of obstruction is variable, and so they may present with mild micturition difficulty or severe obstruction with hydroureteronephrosis and renal impairment. Hence, it is important to evaluate the anterior urethra in any male child with suspected infravesical obstruction. The diagnosis is established by MCU or cystoscopy and the treatment is always surgical, either a transurethral ablation or an open resection. The long-term prognosis is good.

Long-term results of liver transplant in patients with chronic viral hepatitis-related liver disease in Singapore.

INTRODUCTION: Liver disease from chronic hepatitis B (CHB) and C (CHC) constitutes 57 percent of adult liver transplant in Singapore. Their long-term results post-transplant may be affected by recurrence of the viral illness. This study aims to evaluate the long-term results and survival in patients transplanted for CHB- and CHC-related liver disease. METHODS: Patients transplanted for CHB- and CHC-related disease from 1990 until March 2004, which included decompensated cirrhosis and hepatocellular carcinoma (HCC), were reviewed and analysed. RESULTS: 25 patients were transplanted for CHB-related liver disease, with mean follow-up of 153 +/- 25 weeks. Two- and four-year survival rates were 75 percent and 69 percent, respectively. Hepatitis B recurrence from YMDD mutants occurred in five patients, and four were treated successfully with adefovir dipivoxil, with resolution in transaminases and/or improvement in histology. One patient became non-compliant with follow-up and medications, and died 173 weeks post-transplant from reactivation of the wild-type hepatitis B virus. Nine patients were transplanted for CHC-related liver disease, with mean follow-up of 188 +/- 40 weeks, and two- and four-year survival rates of 89 percent and 76 percent, respectively. Two patients developed hepatitis C recurrence and were treated with interferon and ribavarin. One responded with sustained response but the other remained viraemic and died of HCC recurrence two years post-transplant. CONCLUSION: Long-term results from CHB- and CHC-related liver diseases were satisfactory and comparable to major transplant centres in the USA and Europe. Recurrence of viral hepatitis post-transplant is controllable with current antiviral therapy.

MELD may not be the better system for organ allocation in liver transplantation patients in Singapore.

INTRODUCTION: The Model for End-Stage Liver Disease (MELD) score is a good predictor of mortality on the liver transplant waiting list and is the current system of organ allocation in the USA. However, a higher MELD may be associated with poorer outcome post-liver transplantation. The aim of this study was to determine if MELD should be implemented as the system for organ allocation for liver transplantation in Singapore. METHODS: There were 46 adult patients who underwent primary liver transplantation at the National University Hospital, Singapore from January 1996 to December 2002. We applied the MELD score to patients who were transplanted and looked for a correlation with survival post-transplant. Patients were followed-up until the most recent visit or death. Survival analysis was performed using Cox regression and Kaplan-Meier method. RESULTS: The mean age at transplant was 52.7 (SD 2.34) years. The majority of the patients transplanted had Hepatitis B (43 percent). The median MELD score at transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There was a significant correlation between pre-transplant MELD and survival at six months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1) as well as survival for patients with and without Hepatitis B (OR 0.72, 95 percent CI 0.22-2.35). CONCLUSION: MELD allows livers to be allocated to the patients with the greatest medical urgency but its influence on post-transplant survival should be further clarified so that post-transplant survival is not compromised.

Outcome of liver transplantation for children with liver disease.

INTRODUCTION: The advent of liver transplantation has revolutionised the outcome of children with both acute liver failure and chronic end-stage liver disease. The aim of this study was to review the outcome of all paediatric liver transplants performed since the National Liver Transplant Programme began in 1990. METHODS: A retrospective review of all paediatric liver transplants from 1990 to December 2004 was performed. RESULTS: 46 liver transplants were performed in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant was 21 months (range 11 months to 14 years). The most common indication for liver transplant was biliary atresia (71.7 percent). Living-related transplants accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of patients, with a 19.6 percent incidence of acute allograft rejection within the first six months. There were nine deaths. They were related to portal vein thrombosis (three), chronic rejection (one), sepsis (two), post-transplant lymphoproliferative disease (two) and primary graft non-function (one). Overall actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent, respectively. CONCLUSION: Liver transplantation is an established form of intervention for end-stage liver disease and a variety of liver-related metabolic disease. Our results are comparable to those of well-established liver transplant centres.

Referral patterns and waiting times for liver transplantation in Singapore.

INTRODUCTION: Referral patterns, waiting times, waiting list, and mortality provide information on how effectively a transplant programme deals with referred patients. This paper aims to review these parameters in the Singapore National Liver Transplant Programme. METHODS: Data of all patients referred to the Singapore National Liver Transplant Programme since its inception were captured and outcomes were retrieved and described. RESULTS: 562 patients were referred for liver transplant evaluation from 1990-2004, consisting of 457 adults and 105 children. The main indications for referral were hepatitis B liver disease and hepatocellular carcinoma in adults, and biliary atresia in children. Most patients were of United Network of Organ Sharing (UNOS) status 3 or 4 at the time of referral. 114 (20.28 percent) patients had transplants, consisting of 66 adults (14.44 percent) and 48 (45.71 percent) children. 138 adults and ten children were rejected for transplant, mainly for the reason of being "too early". The median waiting time for adults who had transplants was 3.3 months while adults still on the waiting list had been waiting for 16.2 months. The overall waiting list mortality was 44.3 percent, being 52.5 percent in adults and 23.2 percent in children. CONCLUSION: The overall transplantation rate is low and the waiting list mortality is high as a result of low availability of organs, particularly in adults. Paediatric liver transplant appears to have been better at dealing with referred patients but this is probably due to availability of living-related liver transplant. Improvement in these may result from the Human Organ Transplant Act.

Long-term post-liver transplant complications of renal impairment and diabetes mellitus: data from Singapore.

INTRODUCTION: Patients who survive the initial post-liver transplantation period face the development of chronic diseases in the long run. We studied two important complications of liver transplantation, namely: renal impairment and diabetes mellitus. METHODS: We analysed adult patients followed-up for more than one year using data from our liver transplant clinical records. Long-term post-transplant renal impairment (RI) was defined as glomerular filtration rate (GFR) less than 60 ml/min/1.73 square metres and long-term post-transplant diabetes mellitus (DM) was defined as fasting blood glucose more than 7.8 mmol/L, that existed at least one year after liver transplantation. Pre- and post-transplant factors that could be associated with these conditions were examined. RESULTS: Altogether, 35 patients were evaluated. Mean age at transplant was 50 years. Mean duration of follow-up was 58.4 months. There was 11.4 percent of pre-transplant RI and 17.0 percent of pre-transplant DM. Prevalence of post-transplant RI was 43.5 percent at one year and 45.0 percent at four years. Long-term post-transplant RI was associated with renal impairment at six months post-transplant (p-value is 0.033). Prevalence of severe post-transplant RI (GFR is less than 30 ml/min/1.73 square metres) at four years was 5.7 percent. Prevalence of post-transplant DM was 45.5 percent at two years but declined to 5.3 percent at four years. CONCLUSION: Post-transplant renal impairment appears to be a potential long-term problem while post-transplant diabetes mellitus appears to improve with time.