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Objective: Age is sometimes a barrier for acceptance of patients into a hospital‐based obesity service. Our aim was to explore the effect of age on the ability to lose weight through lifestyle interventions, implemented within a hospital‐based obesity service. Design: Retrospective study. Patients: We included a cohort of randomly selected patients with morbid obesity (n = 242), who attended our hospital‐based obesity service during 2005‐2016 and received only lifestyle weight loss interventions. Measurements: Primary outcome measures were percentage weight loss (%WL) and percentage reduction in body mass index (%rBMI) following implemented lifestyle interventions. Data were stratified according to patient age at referral: group 1 (age < 60 years, n = 167) and group 2 (age ≥ 60 years, n = 75). Weight loss was compared between groups, and correlations with age at referral were explored. Results: The duration of hospital‐based weight loss interventions ranged between 1 and 143 months (mean: 38.9 months; SD: 32.3). Baseline BMI at referral differed significantly between groups 1 and 2 (49.7 kgm−2 [SD: 8.7] vs 46.9 kgm−2 [SD: 6.1], respectively; P <.05). Following implemented lifestyle interventions, between groups 1 and 2 there were no differences in %WL (6.9% [SD: 16.7] vs 7.3% [SD: 11.60], respectively; P = NS) or %rBMI (8.1% [SD: 14.9] vs 7.8% [SD: 11.7], respectively; p = NS). Overall, there was no significant correlation between patient age at referral and %WL (r = −.13, p = NS). Conclusions: Older age does not influence the success of weight loss through the implementation of lifestyle modification within a hospital‐based obesity service. Therefore, age per se should not influence clinical decisions regarding acceptance of patients to hospital‐based obesity services. [ABSTRACT FROM AUTHOR]

This study aimed to compare outcomes of hand-sewn and stapler closure techniques of pancreatic stump in patients undergoing distal pancreatectomy (DP). Impact of stapler closure reinforcement using mesh on outcomes was also evaluated. Literature search was carried out using multiple data sources to identify studies that compared hand-sewn and stapler closure techniques in management of pancreatic stump following DP. Odds ratio (OR) was determined for clinically relevant postoperative pancreatic fistula (POPF) via random-effects modelling. Subsequently, trial sequential analysis was performed. Thirty-two studies with a total of 4,022 patients undergoing DP with hand-sewn (n = 1,184) or stapler (n = 2,838) closure technique of pancreatic stump were analyzed. Hand-sewn closure significantly increased the risk of clinically relevant POPF compared to stapler closure (OR: 1.56, p = 0.02). When stapler closure was considered, staple line reinforcement significantly reduced formation of such POPF (OR: 0.54, p = 0.002). When only randomized controlled trials were considered, there was no significant difference in clinically relevant POPF between hand-sewn and stapler closure techniques (OR: 1.20, p = 0.64) or between reinforced and standard stapler closure techniques (OR: 0.50, p = 0.08). When observational studies were considered, hand-sewn closure was associated with a significantly higher rate of clinically relevant POPF compared to stapler closure (OR: 1.59, p = 0.03). Moreover, when stapler closure was considered, staple line reinforcement significantly reduced formation of such POPF (OR: 0.55, p = 0.02). Trial sequential analysis detected risk of type 2 error. In conclusion, reinforced stapler closure in DP may reduce risk of clinically relevant POPF compared to hand-sewn closure or stapler closure without reinforcement. Future randomized research is needed to provide stronger evidence.

Context: Mindfulness strategies may facilitate healthier eating behavior but have not previously been studied in a United Kingdom-based tier 3 obesity service., Objective: To demonstrate the clinical effectiveness of mindfulness as part of newly created group sessions within a tier 3 obesity service., Methods: Recruitment of participants (n = 53, including n = 33 completers) from patients attending a tier 3-based obesity service at University Hospitals Coventry and Warwickshire. Each participant attended four group sessions, at which mindfulness-based eating behavior strategies were taught. Self-reported eating behavior and body weight were assessed at baseline and following completion of attendance at the group sessions. Paired-sample t tests were performed. P < 0.05 was considered significant. Data are reported for the 33 completers. Weight difference was assessed in a retrospective control group of 33 patients who did not attend the group sessions but received the standard multidisciplinary input., Results: There were statistically significant improvements (P = 0.009) in self-reported eating behavior [driven by improvements in "fast-foodism" (P = 0.031)] and reduction in body weight [3.06 kg (SD 5.2 kg), P = 0.002] at 6 months following completion of the group sessions. This was statistically more (P = 0.036) than 6-month weight loss in the control group (0.21 kg). Participants reported improved self-esteem and confidence in self-management of body weight., Conclusion: Application of mindfulness-based eating behavior strategies, taught at group sessions within a tier 3 obesity service, resulted in significant improvement in eating behavior, and facilitated subsequent weight loss over 6 months. Such a strategy has potential for scalability to the wider obese population.

Background: Dynamic changes in glycaemia predominate peri-operatively in patients with type 2 diabetes mellitus (T2DM) undergoing metabolic surgery. There is a lack of consensus and clear guidance on effective glycaemic management of such patients. The aim of this study was to design, pilot, and implement a proforma to improve consistency of glycaemic management and clarity of communication with healthcare professionals following metabolic surgery in patients with T2DM, thereby reducing unnecessary diabetes specialist nurse (DSN) referrals., Methods: A proforma was designed and piloted for 12 months to guide healthcare professionals on managing glycaemic therapies for T2DM patients undergoing metabolic surgery. Glycaemic control (HbA1c) and glycaemic therapies were reviewed 3 weeks pre-operatively and a proforma was completed accordingly., Results: Of the patients with T2DM (n = 34) who underwent metabolic surgery prior to the new proforma being implemented, 71% (n = 24) had a DSN referral. Half of these referrals were deemed unnecessary by the DSNs. Of the patients with T2DM (n = 33) who underwent metabolic surgery following implementation of the proforma, 21% (n = 7) had a DSN referral. Only 10% of these were deemed unnecessary. Despite the reduced DSN input, no diabetes-related complications were reported., Conclusion: Implementation of our proforma effectively halved the proportion of patients with T2DM requiring a DSN referral. Additionally, there was a 40% absolute reduction in the proportion of unnecessary DSN referrals. The proforma improved clarity of communication and guidance for healthcare professionals in the glycaemic management of patients. This also facilitated improved work efficiency and resource allocation.

Background: Blood group is reported to have an effect upon survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma. The effect of blood group is not known, however, among patients with other periampullary cancers. This study sought to review this., Methods: Data were collected for a range of factors and survival outcomes from patients treated at two centres. Those with blood groups B and AB were excluded, due to small numbers. Patient survival was compared between patients with blood groups O and A using multivariable analysis which accounted for confounding factors., Results: Among 431 patients, 235 (54.5%) and 196 (45.5%) were of blood groups A and O respectively. Baseline comparisons found a significant difference in the distribution of tumour types (p = 0.011), with blood group O patients having more ampullary carcinomas (33.2% vs 23.4%) and less pancreatic ductal adenocarcinomas (45.4 vs 61.3%) than group A. On multivariable analysis, after accounting for confounding factors including pathologic variables, survival was found to be significantly shorter in those with blood group A than group O (p = 0.047, HR 1.30 [95%CI: 1.00-1.69])., Conclusions: There is a difference in the distribution of blood groups across the different types of periampullary cancers. Survival is shorter among blood group A patients., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The demand for kidney retransplantation following graft failure is rising. Repeat transplantation is often associated with poorer outcomes due to both immunological and surgical challenges. The aim of this study was to compare surgical and functional outcomes of kidney retransplantation in recipients that had previously had at least two kidney transplants with a focus on those with antibody incompatibility., Methods: We analyzed 66 patients who underwent renal transplantation at a single center between 2003 and 2011. Consecutive patients receiving their 3rd or 4th kidney were case-matched with an equal number of 1st and 2nd transplants., Results: Twenty-two 3rd and 4th kidney transplants were matched with 22 first and 22 seconds transplants. Operative times and length of stay were equivalent between the subgroups. Surgical complication rates were similar in all groups (22.7% in 1st and 2nd transplants, and 27.2% in 3rd/4th transplants). There was no significant difference in patient or graft survival over 5 years. Graft function was similar between transplant groups at 1, 3, and 5 years., Conclusions: Third and fourth kidney transplants can be performed safely with similar outcomes to 1st and 2nd transplants. Kidney retransplantation from antibody-incompatible donors may be appropriate for highly sensitized patients., (© 2017 The Authors Clinical Transplantation Published by John Wiley & Sons Ltd.)

Purpose: To determine the prevalence of complementary and alternative medicine (CAM) use in patients with low back pain (LBP) and to identify its correlation with demographic factors, clinical condition and psychosocial factors., Methods: A cross-sectional study was conducted with 278 LBP patients. Use of CAM, demographic parameters and disease duration were determined. Self-reported health status and self-rated scales assessed the effect of disease on quality of life and emotional well-being, respectively. Satisfaction with orthopaedic care and belief partiality towards CAM were assessed., Results: In all, 72.3% patients sought CAM treatment. The most common choice of CAM was traditional Chinese medicine (TCM; n = 166), followed by massage therapy ( n = 114) and chiropractic treatment ( n = 45). Within TCM, acupuncture was the most popular treatment for LBP ( n = 127). Only 32.5% patients informed their doctors of their CAM use. In univariate analyses, factors positively associated with CAM use included duration of LBP (odds ratio (OR) = 1.45, 95% confidence interval (CI): 1.06-1.97), use of CAM in close social circles (OR = 1.98, 95% CI: 1.15-3.43) and summary score for belief partiality towards CAM (OR = 1.18, 95% CI: 1.13-1.23). Variables negatively and significantly associated with status of CAM use include age (OR = 0.97, 95% CI: 0.95-0.99) and summary score for satisfaction with orthopaedic care (OR = 0.93, 95% CI: 0.88-0.99)., Conclusion: CAM use in patients with LBP is prevalent and largely unknown to their doctors. Personal beliefs and their satisfaction with conventional medical treatment both play a part in their decisions to use CAM. Future studies may aim at understanding the effect of CAM on patient adherence to conventional medical treatment and patients' perception of well-being and pain.

Serum aminotransferases have been used as surrogate markers for liver ischemia-reperfusion injury that follows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase (ALT) correlate with patient outcome after liver resection. We assessed whether postoperative day 1 (POD 1) ALT could be used to predict patient morbidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our institution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient's morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver significantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because of the low number of mortalities. Patients undergoing concurrent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not correlate with patient morbidity after elective liver resection.

Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) (p<0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others (p<0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels., (Copyright © 2015. Published by Elsevier Inc.)

Introduction: Delayed graft function (DGF) remains a significant and detrimental postoperative phenomenon following living-related renal allograft transplantation, with a published incidence of up to 15%. Early therapeutic vasodilatory interventions have been shown to improve DGF, and modifications to immunosuppressive regimens may subsequently lessen its impact. This pilot study assesses the potential applicability of perioperative non-invasive cardiac output monitoring (NICOM), transit-time flow monitoring (TTFM) of the transplant renal artery and pre-/perioperative thromboelastography (TEG) in the early prediction of DGF and perioperative complications., Methods: Ten consecutive living-related renal allograft recipients were studied. Non-invasive cardiac output monitoring commenced immediately following induction of anaesthesia and was maintained throughout the perioperative period. Doppler-based TTFM was performed during natural haemostatic pauses in the transplant surgery: immediately following graft reperfusion and following ureteric implantation. Central venous blood sampling for TEG was performed following induction of anaesthesia and during abdominal closure., Results: A single incidence of DGF was seen within the studied cohort and one intra-operative (thrombotic) complication noted. NICOM confirmed a predictable trend of increased cardiac index (CI) following allograft reperfusion (mean CI - clamped: 3.17 ± 0.29 L/min/m(2), post-reperfusion: 3.50 ± 0.35 L/min/m(2); P < 0.05) mediated by a significant reduction in total peripheral resistance. Reduced TTFM at the point of allograft reperfusion (227 ml/min c.f. mean; 411 ml/min (95% CI: 358 to 465)) was identified in a subject who experienced intra-operative transplant renal artery thrombosis. TEG data exhibited significant reductions in clot lysis (LY30 (%): pre-op: 1.0 (0.29 to 1.71), post reperfusion 0.33 (0.15 to 0.80); P = 0.02) and a trend towards increased clot initiation following allograft reperfusion., Conclusions: Reduced renal arterial blood flow (falling without the 95% CI of the mean), was able to accurately predict anastomotic complications within this pilot study. TEG data suggest the emergence of a prothrombotic state, of uncertain clinical significance, following allograft reperfusion. Abrogation of characteristic haemodynamic trends, as determined by NICOM, following allograft reperfusion may permit prediction of individuals at risk of DGF. The findings of this pilot study mandate a larger definitive trial to determine the clinical applications and predictive value of these technologies.

Background: HLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation., Methods: 55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified., Results: Despite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00)., Conclusion: In spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection.

Background: Intraperitoneal local anesthesia (IPLA) during elective laparoscopic cholecystectomy (el-LC) decreases post-operative pain. None of the studies have explored the efficacy of IPLA at emergency laparoscopic cholecystectomy (em-LC). A longer operative duration, the greater frequency of washing, and the inflammation associated with cholecystitis or pancreatitis are a few reasons why it cannot be assumed that a benefit in pain scores will be seen in em-LC with IPLA. This study was undertaken to assess the efficacy of IPLA in patients undergoing em-LC., Methods: Double-blind randomized sham controlled trial was conducted of 41 consecutive subjects undergoing em-LC. IPLA was delivered by a combination of injection to the diaphragmatic and topical wash over the liver and gallbladder with bupivacaine or saline. The primary outcome was visual analogue scale pain scores until discharge. Secondary outcomes included pain scores in theatre recovery and analgesic consumption., Results: One patient had a procedure converted to open and was excluded. There was no significant difference in pain scores in the ward or theatre recovery. Analgesic use, respiratory rate, oxygen saturation, duration to ambulation, eating, satisfaction scores, and time to discharge were comparable between the two groups., Conclusions: IPLA during em-LC does not influence postoperative pain. Other modalities of analgesia should be explored for decreasing the interval between diagnosis of acute admission and em-LC.

Background: The role of the complement system in antibody-mediated rejection has been investigated in relation to circulating complement interacting with renal microvascular endothelium, resulting in the formation of peritubular capillary C4d. However, the possible importance of local complement synthesis is less clear. The aim of this study was to determine whether human vascular endothelium could produce C4 in response to stimulation in vitro., Methods: Human microvascular endothelial cells and glomerular endothelial cells were stimulated with endotoxins, cytokines, and human leukocyte antigen-specific antibodies. Synthesis of complement was investigated using western blotting and indirect immunofluorescence. De novo C4 synthesis was confirmed by using C4 small interfering RNA., Results: Glomerular and microvascular endothelium, both produce C3 and C4 complement protein. Complement synthesis was stimulant-specific-C3 was produced mainly after stimulation with lipopolysaccharide whereas C4 synthesis occurred on treatment with gamma interferon. Culture with human leukocyte antigen-specific antibodies resulted in a significant increase of C4 protein synthesis by both cell lines., Conclusions: We have shown for the first time that human microvascular endothelium can be stimulated to synthesize C4 in vitro. The implications of this for clinical transplantation, especially in the context of antibody-mediated rejection, its histological interpretation and as a potential target for therapy would have to be determined by further studies.

Background: Human leukocyte antigen (HLA) antibody-incompatible renal transplantation has been increasingly performed since 2000 but with few data on the medium-term outcomes., Methods: Between 2003 and 2011, 84 patients received renal transplants with a pretreatment donor-specific antibody (DSA) level of more than 500 in a microbead assay. Seventeen patients had positive complement-dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed 28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with plasmapheresis pretransplant, and patients did not routinely receive antithymocyte globulin posttransplant., Results: Mean follow-up posttransplantation was 39.6 (range 2-91) months. Patient survival after the first year was 93.8%. Death-censored graft survival at 1, 3, and 5 years was 97.5%, 94.2%, and 80.4%, respectively, in all DSA+ve patients, worse at 5 years in the CDC+ve than in the CDC-ve/DSA+ve group at 45.6% and 88.6%, respectively (P<0.03). Five-year graft survival in the DSA-ve group was 82.1%. Rejection occurred in 53.1% of DSA+ve patients in the first year compared with 22% in the DSA-ve patients (P<0.003)., Conclusions: HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.

Gastrointestinal stromal tumours often present with insidious upper gastrointestinal symptoms. Initial definitive diagnosis can be difficult and therefore misdiagnosis is not infrequent. Here we report a case of upper GI bleeding caused by a splenic artery aneurysm that was misdiagnosed as a gastric GIST. This rare presentation of splenic artery aneurysm highlights the potential pitfalls of investigation in upper gastrointestinal disease., (© JSCR.)

Double filtration plasmapheresis (DFPP) was used in preference to plasma exchange in our program of antibody-incompatible transplantation, to treat higher volumes of plasma. Forty-two patients had 259 sessions of DFPP, 201 pre-transplant and 58 post-transplant. At the first treatment session, the mean plasma volume treated was 3.81 L (range 3-6 L), 55.5 mL/kg (range 36.2-83.6 mL/kg). Serum IgG fell by mean 59.4% (SD 10.2%), and IgM by 69.3% (SD 16.1%). Nine patients did not require increases in plasma volumes treated, and six did not tolerate higher plasma volumes. In the remaining patients, the mean maximum plasma volume treated pre-transplant was 6.67 L (range 4-15 L), 96.1 mL/kg (range 60.2-208.9 mL/kg). The complement dependent cytotoxic crossmatch was positive in 14 cases pre-treatment, and remained positive in six (42.8%) cases. The flow cytometric crossmatch was positive in 29 cases pre-treatment, and in 21 (72.4%) after DFPP. Post-transplant, DFPP was ineffective at reducing donor specific antibody levels during periods of rapid donor specific antibody synthesis. Post-transplant, the one year graft survival rate was 94%, although there was a high rate of early rejection. In summary, DFPP enabled the treatment of plasma volumes that were almost double those that would have been feasible with plasma exchange. Despite this, most patients were transplanted with a positive crossmatch, and DFPP post-transplant was unable to control rising antibody levels.

HLA antibody-incompatible transplantation has a higher risk of rejection when compared to standard renal transplantation. Soluble CD30 (sCD30) has been shown in many, but not all, studies to be a biomarker for risk of rejection in standard renal transplant recipients. We sought to define the value of sCD30 and soluble CD27 (sCD27) in patients receiving HLA antibody-incompatible transplants. Serum taken at different time points from 32 HLA antibody-incompatible transplant recipients was retrospectively assessed for sCD30 and sCD27 levels by enzyme-linked immunosorbent assay (ELISA). This was compared to episodes of acute rejection, post-transplant donor-specific antibody (DSA) levels and 12 month serum creatinine levels. No association was found between sCD27 and sCD30 levels and risk of acute rejection or DSA levels. Higher sCD30 levels at 4-6 weeks post-transplantation were associated with a higher serum creatinine at 12 months. Conclusion patients undergoing HLA antibody-incompatible transplantation are at a high risk of rejection but neither sCD30 (unlike in standard transplantation) nor sCD27 was found to be a risk factor. High sCD30 levels measured at 4-6 weeks post-transplantation was associated with poorer graft function at one year., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to examine the development of acute antibody-mediated rejection in HLA antibody-incompatible renal transplantation in relation to the Banff 07 histological classification., Methods: Renal biopsies were scored using the Banff 07 diagnostic criteria, and paraffin-embedded sections were stained with the pan-leucocyte marker CD45., Results: Thirty-six patients had 72 renal biopsies. In biopsies performed 30 min after graft reperfusion, the mean number of CD45+ cells per glomerulus was higher than in control grafts (P < 0.04) and was associated with the donor-specific antibody (DSA) level at transplantation measured by microbeads (P < 0.01), and eight out of nine patients with greater than five CD45+ cells per glomerulus had early post-transplant rejection or oliguria, compared to 11 out of 20 with less than five cells per glomerulus (P < 0.01). In the first 10 days post-transplant, although peritubular capillary (PTC) leucocyte margination grade 3 and C4d deposition were specific for rejection, their sensitivities were low. PTC C4d staining was only seen in two out of 11 biopsies taken in the first 5 days after transplant, even in the presence of rejection, but was present in the majority of later biopsies with rejection. In biopsies stained for CD3, CD68 and CD20, it was notable that CD20+ cells were not seen during acute rejection, the infiltrates comprising CD3+ and CD68+ leucocytes., Conclusions: Glomerular margination of leucocytes occurred early after transplantation and was associated with DSA level and early graft dysfunction. The Banff 07 PTC margination scoring system was easy to apply, especially when CD45 staining was used, and PTC margination grade 3 was always associated with clinical rejection.

Current methods of measuring ABO antibody levels based on the hemagglutination (HA) titers have the disadvantages of relatively poor reproducibility and do not offer fine discrimination of antibody concentration. We therefore developed a simple and rapid method of measuring ABO antibody levels using flow cytometry (FC). For validation, we analyzed plasma samples from 79 blood donors. Both IgM and IgG were detected and measured with IgG essentially restricted blood group O donors. Forty-two successive samples were collected from a patient with blood group O undergoing antibody removal and subsequent transplantation from a group A2 donor and tested by both HA and FC. Changes in IgG measured by FC (relative median fluorescence) correlated well with HA titers and importantly rejection episodes were preempted by a rising relative median fluorescence. The method allowed quantitative discrimination in the range of antibody levels relevant to ABO incompatible transplantation and has the advantages over HA of objective measurement and reproducibility.

Background: The minor histocompatibility antigen HA-1 occurs in two allelic forms: H and R. The HA-1(H) form presented in the context of HLA A2 can elicit specific cytotoxic lymphocyte (CTL) responses and can cause graft-versus-host disease in marrow transplants. However, its significance in solid organ transplants is unknown. We determined whether incompatibility of the HA-1 resulted in enhanced rejection and whether HA-1 specific CTLs were generated., Materials and Methods: HLA A2-matched donor/recipient pairs were selected and typed for HA-1 antigens by polymerase chain reaction. Nineteen of 81 pairs were mismatched for HA-1. Peripheral blood mononuclear leucocytes from five recipients, HLA A2 DR-matched with donors, were stimulated for 3 days with third-party donor, matched for HLA A2 DR but mismatched for HA-1. Cells were stained for surface markers, HA-1(H)-specific tetramer reagent, and analyzed by flow cytometry. Controls were unstimulated cells; PBML from two patients never exposed to HA-1(H); immunoglobulin G isotype-matched controls. For all patients, acute rejection rates posttransplant was ascertained. Long-term data was available for 36 patients., Results and Conclusions: There was no difference in acute rejection rates between the HA-1-matched and -mismatched groups, but there was a significant difference in chronic rejection rates, evidenced by increased graft failures during the follow-up period (P = .0024). Lymphocytes from five HA-1-mismatched recipients were stimulated in vitro with cells from HLA-A2 and DR-matched but HA-1-mismatched surrogate donor. Though there seemed to be an excess of tetramer-positive cells, anti-HA-1-specific CTL responses were not conclusively elicited in vitro.

It is recommended that cyclosporine dosing should be based on the whole blood level 2 h after a dose (C2), not the trough level (C0). Initial studies did not however establish the outcome of dosing according to C2 levels in long-term patients previously managed by C0 levels. C0 and C2 were measured in 152 stable patients receiving Neoral therapy, mean 86.9 months after transplantation. This showed that 38 (25%) had C2 levels above a target range of 700-900 microg/l. Higher C2 levels were associated with higher cholesterol levels (P = 0.0058) and higher diastolic blood pressure (P = 0.0163). Cyclosporine dose reduction was undertaken in 32 patients with high C2 levels. For logistical reasons, C2 was not performed regularly, but an individualized C0 level was set for each patient. A 16% reduction in mean cyclosporine dose was achieved, associated with a 28% fall in mean C0, from 212 to 153 microg/l, and a 25% fall in mean C2, from 1075 to 820 microg/l. There was no excess in adverse events in the dose reduction cohort, compared with patients with initial C2 levels <900 microg/l. Over a mean 15 month follow-up period in the dose reduction cohort, there was a 4.4% reduction in mean diastolic blood pressure, from 84.9 (SEM 2.1) to 80.2 (1.9) mmHg, P = 0.023; and a 10.4% reduction in mean cholesterol, from 5.71 (0.27) to 5.11 (0.25), P = 0.005 (patients starting on statin during follow-up excluded). In patients with initial C2 <900 microg/l, blood pressure did not fall and the cholesterol fell by 3.9%, from 5.27 (0.14) to 5.07 (0.15) mmol/l (P = 0.0405). In conclusion, cyclosporine dose reduction was safe in stable long-term renal allograft recipients with high C2 levels. There was an improvement cholesterol levels and a small improvement in blood pressure after cyclosporine dose reduction.

Background: The authors investigated the relationship between therapeutic blood transfusion before renal transplantation and rejection rates in cyclosporine- and tacrolimus-treated patients., Methods: In one center, 265 consecutive recipients were studied. Protocol induction was with azathioprine, prednisolone, and cyclosporine or tacrolimus; 37% had biopsy-proven acute rejection in the first 6 months and 46% had received zero to two units of blood before transplantation., Results: Lower risk of rejection was associated with tacrolimus induction (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.29-0.95; P=0.049), prior transfusion of three or more units of blood (OR, 0.54; 95% CI, 0.33-0.90; P=0.024), and older age at transplantation (mean, 44.23 +/- 12.56 [+/- SD] years vs. 38.96 +/- 12.37 years; P=0.001). Multiple logistic regression modeling showed the effect of three or more prior transfusions on acute rejection was as follows: OR, 0.49; 95% CI, 0.29 to 0.83; P=0.008., Conclusions: Induction immunosuppression should take account of the higher risk of rejection in patients coming to transplantation who have previously received zero to two units of blood.

Background: Conversion from tacrolimus to cyclosporin has not previously been reported as routine clinical practice, but only as indicated by rejection or adverse effects., Methods: The safety and metabolic outcome of elective conversion from tacrolimus to cyclosporin was examined in 19 recipients of cadaver renal transplants. Conversion was performed in stable patients at 3-6 months after transplantation., Results: Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0.65-1) mmol/liter (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/liter (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporin (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration postdose (Cmax), minimum concentration postdose (Cmin), time to maximum concentration (Tmax)., Conclusion: This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporin-based immunosuppression in stable patients after renal transplantation. This conversion was performed without early immunological hazard, but there was a small rise in blood cholesterol levels after conversion. Pharmacokinetic studies showed cyclosporin in the form of Neoral showed less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.

We report a case of metastasis from a regressed cutaneous melanoma presenting as an acute abdomen. The patient presented with peritonitis, which at operation was found to be due to intraperitoneal haemorrhage from a bleeding metastatic melanoma lesion in the ileum. Surgical resection was performed and the patient remained well 2 years later.

A case report of a 23 year old man is described who was diagnosed with loin pain/haematuria syndrome. Despite auto-transplantation with interposed polytetrafluoroethylene (PTFE)-prosthesis in the arterial anastomosis the symptoms recurred. A possible mechanism for the recurrent pain is proposed.

Shortage of donor organs has become on of the most important limiting factors in the field of transplantation. Suitability of organs from patients dying from poisoning is an unexplored area. This is because of the suspicion that the organs, in particular the liver and the kidneys, might have been irreversibly damaged by the poison. We report a case of cyanide poisoning in which the kidneys and corneas were harvested after the level of poison fell to below lethal concentration. These organs were later transplanted without any evidence of adverse effects at follow-up.

We examined changes in the circulating T-cell subsets and their activation to see if consistent changes occur following renal transplantation, during acute rejection episodes (ARE), cytomegalovirus (CMV) infection, and cyclosporine (CsA) nephrotoxicity. Serial blood samples were taken from 28 patients on standard triple immunosuppresion therapy. Using two-colour flow cytometric analysis, the percentages of CD3+, CD4+, and CD8+ T-cells were determined, and coexpression of CD25, HLA/DR, and CD45 isoforms used to define their activation status. During ARE and CMV infection, increased levels of circulating CD4+ CD25+, CD8+ HLA/DR+, CD4+ CD45RO+, CD8+ CD45RO+ were observed. The increased levels of CD45RO+ T-cells were associated with a significant decrease in the percentages of CD45RA+ of both CD4+ and CD8+ T-cells. No significant changes were seen during CsA nephrotoxicity. The pattern of marker expression seen during ARE and CMV infection was similar to that seen in Con-A stimulated T-lymphocytes from 22 normal controls. We conclude that, the increase in the levels of these surface markers do not differentiate between lymphocyte activation indicative of rejection or infection, but clearly distinguish episodes of CsA nephrotoxicity. These results could be useful in the differential diagnosis of renal allograft dysfunction.

Background: Even in low doses, long-term steroid immunosuppression is known to cause serious complications. However, the safety of steroid withdrawal has not been proven in randomized clinical trials. This study examines donor-specific hyporesponsive transplant recipients before and after steroid withdrawal, to see if reduction in immunosuppression was associated with consistent changes in antidonor immunological reactivity., Methods: Using limiting dilution assays, the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) were determined in 21 consecutive cadaveric renal allograft recipients on standard triple therapy, before (pre-tx) and at different time points after transplantation (post-tx). Patients were selected for steroid withdrawal by clinical criteria (stable graft function and no or only one very mild rejection episode)., Results: Of 21 patients studied, steroids were successfully withdrawn in nine (steroid withdrawn group, SWG) for at least 187 days (mean: 380 +/- 168.5), and were not withdrawn in 12 patients (steroid continued group, SCG). In the SWG seven of nine patients developed at least fivefold reduction of post-tx donor-reactive HTLpf (range 5-17), relative to pre-tx, as compared to two of twelve patients in the SCG, P = 0.01. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. In the SWG, no significant difference of serum creatinine level was found before and at 6 months after steroid withdrawal (mean: 138 +/- 24 versus 132 +/- 40, P = 0.45)., Conclusion: Patients who developed donor-specific hyporeactivity as evidenced by low donor-reactive HTLpf had stable graft function and stable HTLpf levels after complete steroid withdrawal.

This prospective randomized trial examines the effect of a "reflush" with preservation solution immediately prior to renal allograft implantation, using hyperosmolar citrate (HOC, n = 10) or phosphate-buffered sucrose (PBS140, n = 10) versus no reflush (n = 10). All kidneys had been stored in HOC. The HOC reflush did not alter the postpreservation intra- or extracellular electrolyte milieu, whereas the PBS140 reflush resulted in an apparent overall loss of both sodium and potassium from the kidney (P < 0.0005). A small amount of calcium was released into the venous effluent in both reflush groups. A similar amount of lactic acid was released into the venous effluent of the two reflush groups, reflected by a lower pH (P < 0.0005), and there was a similar loss of lactate dehydrogenase and creatine phosphokinase. An analysis of procoagulant activity in the first urine produced was performed as a marker of reperfusion injury. The median value was higher in the No Reflush group at 457.5 units, compared with 263.0 and 209.0 units for the PBS140 and HOC Reflush groups, respectively (P = 0.06). Reflushing the kidneys reduced the postoperative dialysis requirement (from 40% to 15%), but by the end of the first posttransplant week there was no significant difference between the renal functional analyses of the three groups, and there was no difference at one year. The proposed mechanism for the early renal functional improvement is a reduction in the calcium paradox and free radical formation, by release of calcium and ATP breakdown products into the venous effluent prior to implantation.

Ranolazine is a new drug with a novel mode of action as a metabolic modulator and membrane stabilizer. In this prospective randomized double-blind trial, a porcine model of renal autotransplantation was used to assess the effects of this drug during preservation and reperfusion of kidneys cold-stored for 24 hr in phosphate-buffered sucrose (PBS140). Three groups of 10 animals were compared: a Placebo group (placebo given intravenously to the animal before nephrectomy, added to the preservation solution, and given again to the animal during reperfusion); a Storage group (Ranolazine before and during storage, placebo during reperfusion); and a Reperfusion group (placebo before and during storage, Ranolazine during reperfusion). Detailed analysis of posttransplant renal function was carried out over a 14-day follow-up period. There were 7 deaths with primary nonfunction: 2 Placebo, 1 Storage, 4 Reperfusion. Analysis of the whole group and separate analysis of the survivors demonstrated significantly improved glomerular (P less than 0.05), tubular (P less than 0.05), and loop of Henle (P less than 0.05) function in the Storage group. The results of this study clearly demonstrate the beneficial effects of Ranolazine during the storage phase of porcine renal preservation, and further investigation of this drug is warranted.

The result of this study shows that a simple phosphate buffered sucrose solution (PBS) is better than hyperosmolar citrate (HOC) solution in the flush perfusion and hypothermic storage of canine kidneys for 72 hr prior to autotransplantation with immediate contralateral nephrectomy. The peroperative measurement of postreperfusion renal blood flow revealed a significant reduction after 60 min in kidneys preserved with HOC solution. All grafts and animals in the PBS group (5/5) survived with primary renal function compared with one in the HOC group (1/5), which functioned after a period of oliguria. The early serum creatinine and urea levels were significantly lower in the PBS group, with a return to normal range within two weeks. This is reflected in higher inulin clearances and a more rapid recovery of proximal tubular function in the PBS animals, which also demonstrated a more rapid return of loop function and the ability to concentrate urine.

Three cases of complicated oriental cholangiohepatitis are described in patients of Asian origin. The development of high biliary strictures in two patients required liver resection; in the third patient the process was complicated by a presumed bile duct malignancy. Oriental cholangiohepatitis may be expected in UK surgical practice given the increased frequency of migration from Asia.

This retrospective study has revealed that human cadaveric renal grafts preserved with hypertonic citrate solution have a significantly higher proportion with primary graft function compared with EuroCollins preserved grafts. Furthermore, Hypertonic citrate-preserved grafts have better early renal function. Those grafts with primary function show an improved graft survival at 12 months when compared with those grafts which had delayed function. There was no difference in renal graft function at 6 months following transplantation between the hypertonic citrate and EuroCollins-preserved grafts nor in the graft losses from rejection. Although the overall graft failure rate in the hypertonic citrate group is higher, this is due to patient mortality and not to rejection.