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Matthew Cooper

Publications and source records attributed to Matthew Cooper.

12 recordsLinked to original sources
PubMed2026

Comparison of long-term outcomes between liver transplantation and liver resection for intrahepatic cholangiocarcinoma: An updated systematic review and meta-analysis.

BACKGROUND: Liver resection (LR) has been the standard treatment for intrahepatic cholangiocarcinoma (ICC), but is associated with high recurrence rates and poor prognosis. Recently, outcomes for liver transplantation (LT) in highly selected ICC patients have significantly improved. This review compares the long-term prognosis of LT versus LR for ICC. METHODS: A systematic review of databases including Web of Science, MEDLINE, Scopus, and Cochrane CENTRAL for comparative studies on the long-term outcomes of LT versus LR for ICC was completed. The primary outcome was 5-year overall survival (OS). Meta-analysis was performed using random-effects models. RESULTS: A total of 7 retrospective comparative studies were included. A total of 5478 patients were analyzed (LT group: 346 patients; LR group: 5132 patients). Pooled analysis showed significantly improved long-term prognosis in the LT group compared to the LR group. Five-year OS was higher in the LT group (OR 0.59, 95% CI 0.37- 0.93, p = 0.02) and 5-year recurrence-free survival (RFS) was also higher in the LT group (OR 0.44, 95% CI 0.22- 0.89, p = 0.02), although the comparison of 1-year OS (p = 0.52) and 3-year OS (p = 0.88) between the LT and LR groups showed no significant difference. However, sensitivity analysis revealed that excluding one study resulted in changes to the statistical significance of both 5-year OS and 5-year RFS. This suggests that individual studies have some influence. CONCLUSIONS: LT may be associated with improved long-term survival and recurrence outcomes compared with LR for ICC; however, the evidence is limited and should be interpreted with caution. These findings suggest a potential benefit of LT in carefully selected patients, but further prospective studies are needed to confirm these results.

Humans↗
PubMed2006

The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivo.

ABCA1 promotes cholesterol efflux from cells and is required for maintaining plasma cholesterol levels. Cholesterol homeostasis is important in the production of beta-amyloid (Abeta), a peptide that is overproduced in Alzheimer's disease (AD). Overexpression of ABCA1 can be achieved by stimulating Liver X Receptors (LXR), and changes in Abeta have been reported after LXR stimulation in vitro. To determine whether ABCA1 could alter endogenous Abeta levels, we used two different in vivo systems. We first examined the effects of an LXR agonist (TO-901317) on wild-type mice and found an increase in brain ABCA1 and apoE levels, which caused an increase in plasma cholesterol. This was accompanied by a decrease in brain Abeta levels. We then examined endogenous Abeta levels in ABCA1 knockout mice and found that, despite having no ABCA1, lowered brain apoE levels, and lowered plasma cholesterol, there was no change in Abeta levels. To assess these in vivo models in an in vitro system, we designed a model in which cholesterol transport via ABCA1 (or related transporters) was prevented. Switching off cholesterol efflux, even in the presence of TO-901317, caused no change in Abeta levels. However, when efflux capability was restored, TO-901317 reduced Abeta levels. These data show that promoting cholesterol efflux is a viable target for Abeta reducing strategies; however, knockout of cholesterol transporters is not sufficient to alter Abeta in vitro or in vivo.

ATP Binding Cassette Transporter 1↗
PubMed2005

ABO incompatible high-titer renal transplantation without splenectomy or anti-CD20 treatment.

Most successful protocols for renal transplantation across ABO incompatible (ABOi) barriers have utilized splenectomy as part of the pre-conditioning process. We recently described successful ABOi transplantation using anti-CD20 monoclonal antibody in lieu of splenectomy. In the current study, we hypothesized that plasmapheresis (PP) and low dose CMV hyper-immunoglobulin (CMVIg) alone would be sufficient to achieve successful engraftment of ABOi kidneys. We describe four blood type incompatible patients who received live donor renal transplants from A1 (two patients), A2 (one patient), and B (one patient) donors. All patients started with antihuman globulin (AHG) phase titers of 64 or higher and were pre-conditioned with PP/CMVIg but not splenectomy or anti-CD20. All 4 patients underwent successful transplantation and have a mean current serum creatinine of 1.1 (range: 0.9-1.2). There were no episodes of antibody mediated rejection. Rapid allograft accommodation may limit the need for long-term antibody suppression provided by splenectomy or anti-CD20, thereby eliminating the added infectious risk of these modalities and removing another disincentive to ABOi transplantation.

ABO Blood-Group System↗
PubMed2005

Modulating alloimmune responses with plasmapheresis and IVIG.

Antibody-mediated barriers to renal transplantation, including donor specific anti-HLA and anti-blood group antibodies, have become an increasingly important issue over the last forty years as the organ shortage has continued to expand. The inevitable result of the unmet demand for compatible organs has been a continuous increase in recipient waiting times. Over the last decade, two treatment strategies have been developed to address this problem. These regimens rely on the immunomodulatory properties of intravenous immunoglobulin (IVIG) administered alone at relatively high doses, or at lower doses in combination with the non-selective depletion of antibodies from plasmapheresis. Both protocols have been successfully used for desensitization of patients with donor-specific anti-HLA antibody and have allowed for renal transplantation with excellent outcomes. The combined strategy of plasmapheresis/IVIG has also been successfully employed for renal transplantation in recipients of ABO blood group incompatible kidneys. This review will provide an overview of these therapies and their application to incompatible renal transplantation.

ABO Blood-Group System↗
PubMed2004

Selecting for antibody scFv fragments with improved stability using phage display with denaturation under reducing conditions.

Stability of single-chain Fvs (scFvs) can be improved by mutagenesis followed by phage display selection where the unstable variants are first inactivated by, for example, denaturing treatment. Here we describe a modified strategy for the selection of stabilized antibody fragments by phage display, based on denaturation under reducing conditions. This strategy was applied to an anti-thyroid-stimulating hormone (TSH) scFv fragment which refolded remarkably during the selection if denaturation was carried out in conventionally used non-reducing conditions. Refolding was, however, efficiently prevented by combining denaturation with reduction of the intra-domain disulfide bridges, which created favourable conditions for selection of clones with improved stability. Using this strategy, scFv mutants with 8-9 degrees C improved thermal stability and 0.8-0.9 M improved stability for guanidinium chloride were found after 4-5 enrichment cycles. The most stable mutants selected contained either Lys(H)66Arg or Asn(H)52aSer mutations, which are known to stabilize other scFvs. Periplasmic expression level of the mutants was also improved.

Animals↗
PubMed2004

Screening for sight-threatening diabetic retinopathy: comparison of fundus photography with automated color contrast threshold test.

PURPOSE: To compare tritan contrast threshold (TCT) with fundus photography in screening for sight-threatening diabetic retinopathy (STDR), before significant visual loss. DESIGN: Prospective, comparative study. METHODS: A total of 510 consenting diabetic patients attending a hospital-based photographic screening clinic were recruited over a 2-year period. Exclusion criteria included visual acuity of worse than 6/9, previous photocoagulation, and a history of previous eye disease known to affect color vision. The automated TCT test was performed using a computerized cathode ray tube-based technique. Retinal photography was performed using a Polaroid mydriatic fundus camera with a 45 degrees field. Grading of diabetic retinopathy was carried out by an ophthalmologist using slit-lamp biomicroscopy and a 78-diopters lens. Assessments of sensitivity, specificity, and predictive values for both fundus photography and the TCT test were made. RESULTS: Both the fundus photography and TCT test correlated significantly with the presence of STDR (P <.0001, chi(2) test). The TCT test yielded a sensitivity of 94% (95% confidence interval [CI], 73%- 100%) and a specificity of 95% (95% CI, 92%- 96%) for detection of STDR compared with a sensitivity of 88% (95% CI, 66%-97%) and a specificity of 95% (95% CI, 93%-97%) with fundus photography. Combined modality improved overall screening performance. CONCLUSION: The TCT assessment is an effective and clinically viable technique, in comparison with fundus photography, to screen for STDR among a diabetic population. Additionally, our results also showed that combining the TCT test with fundus photography greatly increases the performance of screening for STDR.

Adolescent↗
PubMed2004

Successful renal transplantation across simultaneous ABO incompatible and positive crossmatch barriers.

ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were < or =16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.

ABO Blood-Group System↗
PubMed2003

The hazards of basing acceptance of cadaveric renal allografts on pulsatile perfusion parameters alone.

BACKGROUND: Pulsatile perfusion (PP) is used by some centers to provide information that may aid in the selection of cadaveric renal allografts for transplantation. However, basing organ acceptance on PP parameters alone may lead to the discarding of kidneys from otherwise suitable donors. In this case series, we report the reevaluation and transplantation of kidneys refused by other centers after evaluation with PP. METHODS: Retrospective review of 14 cadaveric kidneys imported for repeat PP at our center after initially poor PP parameters from an outside organ procurement organization resulted in refusal by multiple centers. RESULTS: Median age of donors was 46 (range 21-64), and mean terminal serum creatinine was 1.3+/-0.6 mg/dL. Despite favorable donor characteristics, each kidney was refused by an average of 9.3 centers. Poor PP parameters and concerns about donor quality were the reasons for refusal in the majority of cases. Pulsatile-perfusion parameters at the outside center were poor: mean flow of 103 mL/min/100 g and mean resistance of 0.321 mm Hg/(mL/min/100 g). Repeat PP parameters at our center after importation were markedly improved (flow=167 mL/min/100 g and resistance=0.195 mm Hg/[mL/min/100 g]). Eleven of 14 kidneys were transplanted and currently have acceptable graft function (mean serum creatinine=1.6 mg/dL at a median follow-up of 12 months). CONCLUSIONS: This series describes the successful transplantation of 11 kidneys from acceptable donors that were initially discarded by multiple centers after poor PP parameters were obtained. The good allograft function in these organs emphasizes the importance of considering all donor factors when making allocation decisions.

Adult↗
PubMed2003

Concomitant surgery with laparoscopic live donor nephrectomy.

Routine live donor evaluations reveal unexpected silent pathologies. Herein, we describe our experience treating such pathologies at the time of laparoscopic donor nephrectomy. We have not encountered any previous reports of such an approach. We prospectively collected data on 321 donors. Concomitant surgeries at the time of procurement included two laparoscopic adrenalectomies, one colposuspension, one laparoscopic cholecystectomy, and one liver biopsy. Mean operative time was 321 min (range 230-380), with a mean blood loss of 280 mL (range 150-500). No blood transfusions were required. The left kidney was procured in four cases. The right kidney was obtained on one occasion. Mean hospital stay was 3 days (median 3, range 2-4). No short- or long-term complications have been identified. Mean follow-up time was 2.63 years (median 2.76, range 2.23-2.99). Four of the five kidney recipients were first-time transplants who had not yet started dialysis. Simultaneous surgical interventions at the time of laparoscopic live kidney donation are safe and can be undertaken in selected cases. This practice is beneficial to both the donor and the recipient, and is likely to become more commonplace with changing practice patterns involving donor evaluation and management.

Adenoma↗
PubMed2003

Renal transplantation at the Johns Hopkins Comprehensive Transplant Center.

A stagnant supply of transplantable organs in the face of a relentless burgeoning of transplant waiting lists has created a crisis. Necessity continues to be the mother of invention and as the crisis has deepened it has served as a crucible for the development of new ways to think about perennial problems. Our program has taken a 2-pronged approach to increasing the organ supply for our patients. First, through innovations like the laparoscopic donor nephrectomy, ABO-incompatible and positive-crossmatch transplantation protocols, unconventional paired kidney exchanges, and the use of altruistic donors we have more than doubled our utilization of live donor organs. At the same time, we have developed algorithms and interrogative techniques to enhance the intelligent use of kidneys from expanded criteria donors for patients who do not have an available live donor. The laparoscopic nephrectomy has proven to be a safe and effective way of removing a significant barrier to live donation. Our results from 100 ABOi, (+)XM, and PKE transplants are similar to national statistics for compatible live donor transplants, suggesting that existing paradigms of compatibility can be safely expanded. These encouraging early outcomes and the savings they transmit to the health care system have allowed us to obtain insurance coverage for the InKTP programs, setting the stage for further expansion of these opportunities to broaden the options for patients with end-stage renal disease.

ABO Blood-Group System↗