bluuebunny/crossref_metadata_2025 huggingface dataset:
An innovative benefit‐of‐the‐doubt approach for health system effectiveness: a global case study on amenable mortality
Authors: D'Inverno Giovanna , Santos João Vasco , Camanho Ana S.
Published: September 2024

Health system performance assessment (HSPA) is essential for health planning and to improve population health. One of the HSPA domains is related to effectiveness, which can be represented considering different dimensions. Composite indicators can be used to summarize complex constructs involving several indicators. One example of such efforts is the Healthcare Access and Quality Index from the Global Burden of Diseases Study, in which different causes of mortality amenable to health care are summarized in this index through principal component analysis and exploratory factor analysis. While these approaches use the variance of the indicators, marginal improvement is not considered, that is, the distance to the best practice frontier. In this study we propose an innovative benefit‐of‐the‐doubt approach to combine frontier analysis and composite indicators, using amenable mortality estimates for 188 countries. In particular, we include flexible aggregating weighting schemes and a robust and conditional approach. The dual formulation gives information on the peers and the potential mortality rate reduction targets considering the background conditions. In absolute terms, Andorra and high‐income countries are the most effective regarding healthcare access and quality, while sub‐Saharan African and South Asian countries are the least effective. North African and Middle Eastern countries benefit the most when epidemiological patterns, geographical proximity, and country development status are considered.
Transplantation of kidneys with multiple arteries: No adverse effects on immediate function or long‐term survival
Authors: Lipkowitz George S. , Hong Joon H. , Moglia Robert , Galishoff Mitch , Greenstein Stuart , Glanz Sidney , Gordon David , Butt Khalid M. H.
Published: September 2024

The presence of multiple arteries on renal allografts demands superior technical skill and results in a prolonged anastomosis time. This has been implicated as a cause of delayed graft function and inferior graft survival. The incidence of renal artery stenosis, secondary to the presence of smaller donor vessels, has never been determined. Seven‐hundred‐seventy transplants performed at a single center during the 7‐yr period from January 1979 to December 1985 were retrospectively analyzed. Among the 180 living related transplants, 35 (19.4%) had multiple arteries. Thirty‐one of these kidneys had 2 renal arteries and 4 had 3 renal arteries. Among 590 cadaver donor transplants, 121 (20.5%) had multiple arteries: 106 kidneys had 2, 14 had 3, and 1 had 4 renal arteries. Data was analyzed for initial function, 1‐yr graft and patient survival, and incidence of symptomatic renal artery stenosis documented by arteriography. Transplant renal artery thrombosis was diagnosed by renal scintiscan. The patients were grouped according to source of donor kidney and by immunosuppressive protocol. The single artery and multiple artery groups were similar with respect to donor factors, duration and technique of renal preservation, HLA match grade, recipient risk factors and patient management. There was no significant difference in early function or patient and graft survival between the two groups. There was no instance of acute post‐transplant renal failure in living related donor transplants. The reported increased rate of acute post‐transplant renal failure due to prolonged anastomosis time (in cyclosporine‐treated kidneys) was not reproduced in this study. There was no difference in the incidence of symptomatic renal artery stenosis in single or multiple artery grafts with 1‐ to 7‐yr follow‐up. We conclude that implantation of renal grafts with multiple arteries does not adversely affect the ultimate graft or patient survival. The increased implantation time necessary with multiple arteries does not significantly affect immediate graft function. Additionally, grafts with multiple arteries do not demonstrate an increased incidence of renal artery stenosis, as feared when small vessels are anastomosed. We are encouraged to continue the use of cadaver donor kidneys with multiple vessels, some of which might otherwise be wasted. Furthermore, bilateral multiple arteries in living donors should not constitute a contraindication to kidney donation.
Biopsy‐guided immunosuppressive therapy in the treatment of liver transplant rejection: An individualized approach
Authors: Stock Peter G. , Snover Dale , Payne William , Dunn David L. , Simmons Richard L. , Najarian John S. , Ascher Nancy L.
Published: September 2024

Fifty‐eight consecutive patients who received orthotopic liver transplantation were given triple immunosuppressive therapy (cyclosporine, prednisone and azathioprine) to prevent rejection. Weekly percutaneous biopsy was employed to rapidly diagnose and treat rejection. Mild rejection was initially treated with steroids; moderate‐severe rejection was treated using antilymphoblast globulin with or without steroids depending on severity of the histologic pattern. One‐year actuarial survival was 82% for adult recipients and 65% for pediatric recipients. The incidence of biopsy‐proven rejection was high in both groups (77% in adult patients and 73% in pediatric patients) but relatively easily reversed by individualizing treatment based on the response as gauged by serial biopsy. Rejection was reversed in 12 of 13 patients treated with steroids alone and 21 of 24 patients treated with ALG. Only 2 patients went on to chronic rejection. The incidence of bacterial, fungal and viral infections was similar in patients without rejection and in patients with rejection who were treated with steroids alone. A much higher incidence of infection was seen in patients who received antilymphoblast globulin. Four infectious deaths were related to immunosuppressive therapy. The remainder of infections were readily treated with antimicrobial agents. Thus, triple drug immunoprophylaxis with prompt biopsy‐guided individualized therapy is a satisfactory solution to controlling rejection, without exacerbation of fatal infection.
Simultaneous treatment of concurrent rejection and tissue invasive cytomegalovirus disease without detrimental effects upon patient or allograft survival
Authors: Dunn David L. , Mayoral Jaime L. , Gillingham Kristen J. , Sawyer Mark D. , Kramer Marie A. , Statz Catherine L. , McHugh Lois , Matas Arthur J. , Gores Paul F. , Payne William D. , Sutherland David L R. , Najarian John S.
Published: September 2024

Posttransplant cytomegalovirus (CMV) infection has been directly and temporally correlated with decreased patient and allograft survival. Because of this association, prior dogma has dictated that immunosuppression be decreased or maintained, but not increased, and thus rejection episodes have not been treated during active CMV infection. Since 1987, we have treated a group of patients who developed concurrent (within 1–3 days) mild to moderate acute rejection and mild to moderate tissue invasive CMV disease (TI‐CMV) with antirejection and antiviral therapy simultaneously. 619 patients underwent renal transplantation between 5/7/87 and 12/13/90 [535 kidney (253 living related, 282 cadaver) and 84 kidney‐pancreas]. 18 patients presented with concurrent evidence of TI‐CMV plus acute kidney or pancreas allograft rejection. Treatment consisted of iv ganciclovir (DHPG, 5 mg/kg iv q 12 h, mean = 14.4 days) for TI‐CMV and initial oral or iv steroids (followed by ALG or OKT3 in 13 patients) for rejection. At 30 days, all 18 patients with concurrent TI‐CMV and rejection were successfully treated for CMV without DHPG toxicity, although 2 allografts were lost due to unrelenting rejection requiring nephrectomy. 4 patients developed recurrent TI‐CMV and 1 patient developed recurrent rejection >30 days after simultaneous therapy, all of which were successfully treated. A total of 4 deaths occurred due to the following causes: pulmonary embolus, cerebrovascular accident. Candida sepsis, and Aspergillus sepsis, the latter subsequent to treatment of recurrent rejection. We analyzed outcome in patients who developed TI‐CMV post‐rejection (> 14 days) or TI‐CMV without rejection and who received DHPG. and noted that patient and allograft survival was not statistically different compared to patients who received simultaneous therapy for both disease processes (p>0.05). Recipients with or without rejection who never developed TI‐CMV. however, did exhibit increased patient and allograft survival when compared to those who were treated for TI‐CMV alone or simultaneous TI‐CMV plus rejection (p<0.01). Based upon this analysis, we concluded that: 1) simultaneous treatment of concurrent TI‐CMV and acute rejection is feasible, and 2) this docs not magnify the adverse effects related to TI‐CMV alone, and recommended that: 1) antirejection therapy be instituted with simultaneous administration of DHPG in patient with proven rejection and suspected TI‐CMV. 2) the diagnostic work‐up for CMV and other pathogens should be vigorously pursued in this setting, and 3) if evidence of progression of CMV disease occurs (despite absence of this event in this series) that antirejection therapy be withdrawn.
Surgical complications in 50 adult renal transplant recipients of single kidneys from cadaveric donors aged 11 to 48 months
Authors: Lippman H. , Jacoby K. , McFarlin L. , Nicastro J. , Jones C. , Aaberg R. , Banowsky L.
Published: September 2024

Despite the shortage of cadaver kidneys, there is a general reluctance to accept donors < 5 years of age. A major factor for centers declining to use these small organs is the high rate of surgical complications. From January 1986 through December 1990, 50 kidneys from donors aged 11 to 48 months were transplanted as single units into adult recipients. No allografts were used unless there was an ample aortic cuff to minimize arterial stenosis and thrombosis. All renal veins were anastomosed with interrupted 6–0 silk sutures. Previous studies attributed the high incidence of ureteral complications to the fragile blood supply of the pediatric ureter. To alleviate this problem, a stented high uretero‐ureterostomy or uretero‐pyelostomy was done. The surgical complications in these 50 recipients from donors ≤4 years of age were compared with 319 recipients of adult kidneys: Ped vs Adult, renal artery thrombosis 0/50 vs 2/319 (0.63%) (p = ns); renal artery stenosis 2/50 (4%) vs 1/319 (0.31%) (p = ns); renal vein thrombosis 0 vs 0; ureteral fistula 2/50 (4%) vs 7/319 (2.2%) (p = ns); and ureteral obstruction 0 vs 0 (p = ns). The ureteral blood supply was studied in the discarded organs with methylene blue. These studies demonstrated a rich blood supply to the renal pelvis and upper ureter. The blood supply to the distal lumbar ureter was scanty. It was concluded that kidneys from donors <48 months can be safely transplanted as single units into adult recipients with an incidence of surgical complications that is comparable to adults receiving adult cadaver kidneys.
Fulminant post‐transplant lymphoproliferative disorder presenting as multisystem organ failure
Authors: Stephanian Edic , Brayman Kenneth L. , Manivel J. Carlos , Sutherland David E. R. , Dunn David L.
Published: September 2024

In this report, we describe an aggressive polymorphous monoclonal B‐cell lymphoma that developed in a 34–year‐old diabetic male, 1 month after combined pancreas‐kidney transplantation. A diagnosis of post‐transplant lymphoproliferative disorder (PTLD) was established within 72 hours of admission. The tumor was found to infiltrate the transplanted kidney and peripancreatic lymph nodes, as well as the patient's own liver. Despite early diagnosis and immediate withdrawal of immunosuppression, the clinical course was marked by a “sepsis type” syndrome in which high cardiac output, low systemic vascular resistance, metabolic acidosis, and rapid demise occurred. This case was remarkable for several reasons. First, the tumor involved multiple organs and the clinical course of the patient mimicked Gram‐negative bacterial sepsis with multisystem organ failure. Second, the strikingly accelerated progression of the disease led to death within days of diagnosis, despite standard therapeutic interventions. Third, the malignancy appeared shortly after a 7–d course of anti‐lymphocyte antibody was administered for treatment of biopsy‐proven renal allograft rejection. Review of the literature revealed a small number of similar cases of rapidly fatal PTLD. We analyze the possible pathogenesis of this tumor, and emphasize the need for new, aggressive diagnostic and treatment protocols in the management of fulminant PTLD.
Blood pressure in pediatric heart transplants
Authors: Robitaille P. , Vobecky S. , Chartrand S. , Chartrand C.
Published: September 2024

Systemic hypertension developed in 6 of 13 pediatric heart transplant recipients receiving triple immunosuppressive therapy. Appearance of hypertension was noted in 4 patients during the first month postoperatively and in 2 others at 3 and 6 months, respectively. In all cases, blood pressure could be easily controlled with moderate doses of oral hypotensive medication and hypertension was transient in nature. Thus hypertension, although appearing at a frequent rate, was nevertheless not a serious complication in our patients.
Late reactions during initial OKT‐3 treatment
Authors: Turner Miriam C. , Holman John M.
Published: September 2024

Three patients treated with an initial inductive course of OKT‐3 after cadaveric transplantation experienced reactions 9‐13 days after their first dose. The reactions were compatible with IgE‐mediated anaphylaxis, or resembled serum sickness. The cause of the reactions did not seem to be related to inadequate immunosuppression or to OKT‐3 IgG antibody formation.
Bile cytology versus serum sIL‐2R for monitoring of acute liver allograft rejections
Authors: Roberti Isabel , Lieberman Kenneth , Schwartz Myron , Reisman Lewis , Miller Charles
Published: September 2024

Rejection is a major cause of allograft loss after liver transplantation and is often difficult to diagnose in its early stages. Various tests have been suggested to supplant or supplement liver biopsies in the differential diagnosis of acute rejection (AR) from other causes of impaired organ function. This study was undertaken to evaluate the usefulness of two non‐invasive tests for the monitoring of hepatic allograft recipients. We compared serial testing of serum sIL‐2R levels with results of bile cytology (BC) analysis in their ability to differentiate AR from other causes of graft damage. Bile (from an externally draining T‐tube) and blood samples from 12 liver transplant recipients were collected simultaneously at scheduled intervals during the first 3 months post‐operatively in a prospective study. The assignment of clinical diagnosis and the description of BC were performed by blinded investigators. A total of 42 paired samples randomly chosen from each of the established clinical categories were analyzed: 12 from stable grafts, 10 during the ischemic injury period, 13 during AR and 7 during systemic infections. Serum levels of sIL‐2R(U/ml) were significantly higher during AR (9847 ± 6958) and infections (18 437 ± 11 991) as compared to stable grafts (2457 ± 1852); p < 0.05. Cytological findings in stable grafts were unremarkable and consisted of occasional epithelial (ductal) cells. Inflammatory cells (ICs) were not seen in stable grafts. However, ICs (mostly PMNs) were noted in 70% (7/10) of infections and in 92% (12/13) of AR (p< 0.001 compared with stable grafts). Sensitivity and specificity for each test for the diagnosis of AR was calculated. In conclusion, BC analysis was found to be both more sensitive (92.3% vs 58.3%) and specific (73.7% vs 68.2%) than serum sIL‐2R levels in diagnosing AR after liver transplantation.
Successful revascularization of an orthotopic liver transplant (OLT) with the recipient right gastroepiploic artery
Authors: Radermecker M. A. , Honore P. , Dekoster G. , Dewandre J. M. , Thoorens P. , Jacquet N. , Meurisse M.
Published: September 2024

A technique for revascularizing the arterial supply to an orthotopic liver transplant (OLT) in a 55‐year‐old male afflicted with end‐stage alcoholic liver cirrhosis with portal hypertension is reported. The presence of well‐developed portosystemic collaterals and an unsuitable recipient common hepatic artery necessitated the dissection and liberation of the right gastroepiploic artery (RGEA) for its subsequent use as the recipient arterial source. Posttransplantation, save for an early biliary leak which was corrected promptly, the patient's evolution was uneventful. Two separate celiac angiographic series at 6 weeks and 20 months posttransplantation revealed an excellent flow through the recipient and donor arterial systems. Additionally, the RGEA demonstrated an adaptation in caliber when pre‐ and posttransplantation angiograms were compared. It was concluded that the RGEA is a suitable rescue option for revascularization of OLT's provided it satisfies elementary hemodynamic requirements.
Influence of chronic rejection on the occurrence of monoclonal gammapathies in renal transplant patients
Authors: Hestin D. , Petitpain N. , Mayeux D. , Renoult E. , Chanliau J. , Durand P. Y. , Huu T. Cao , Bertrand F. , Kessler M.
Published: September 2024

To assess the frequency of monoclonal gammapathies (MG) and their origin in immunosuppressed renal transplant patients, a prospective study was conducted in 164 patients who underwent 165 consecutive renal transplantations (RT) from April 1986 to August 1991. Sera were tested by cellulose acetate electrophoresis before RT and every 3 months after RT, and those containing a monoclonal component were further investigated by immunoelectrophoresis and/or immunofixation. The immunosuppressive regimen in 69 cases (41.8%) consisted of the association cyclosporinc ‐ prednisone while 96 patients (58.2%) received azathioprine in combination. Sera were regularly monitored by serological assays to detect antibodies against cytomegalovirus (CMV), Epstein‐Barr virus (EBV) and hepatitis B virus. Renal function was evaluated every 6 months by measurement of serum creatinine and quantification of proteinuria. Mean duration of follow‐up was 31.2 months ±15.9 (range 4‐62.4). Thirty‐eight (23.03%) patients developed a MG during this period (26 men, 12 women, mean age: 43.4± 11 years). MG occurred early after RT (6.7 ±7 months) and were often transient (30/38 disappeared after a period of 8.4 ± 12 months). Twenty‐four of the 38 MG were of the gamma 2 ‐ kappa 2 immunologic type whereas 8 were of the biclonal or oligoclonal type. Only moderate quantities of monoclonal component were secreted (9.4 ±2 g/1). Clinical and laboratory examinations excluded the presence of lymphoproliferative disorders of multiple myeloma. No correlation was found for sex, age, underlying renal disease, immunosuppressive regimen, number of HLA matches, and viral infections. The number of acute rejection episodes was similar in the two groups. Conversely, MG were found with a higher frequency in the group of patients who had evidence of chronic rejection (13/27 vs 25/137, p<0.01). Serum creatinine was higher in MG patients from the 36th month after RT (p<0.05). No difference was noted for proteinuria. We conclude that MG are frequently encountered in RT, especially in patients with deteriorating renal function. Since MG results in the uncontrolled proliferation of a B‐cell clone, it can be assumed that chronic rejection favors the occurrence of MG by enhancing the imbalance between the T‐ and B‐cell immune system.
Large interindividual variability in bioavailability of azathioprine in renal transplant recipients
Authors: Ohlman S. , Lafolie P. , Lindholm A. , Liliemark J. , Tydén G. , Peterson C.
Published: September 2024

Azathioprine (Aza), one of the first immunosuppressive agents that proved successful in clinical transplantation, is still widely used. The drug is given in standardized doses which are adjusted only when signs of myelotoxicity occur. It has only recently become possible to specifically determine the level of Aza in plasma. In this study the plasma concentrations of Aza and its primary metabolite 6‐mercaptopurine (6‐MP) were measured after an oral and an equally large intravenous dose of Aza had been administered to 6 recipients of cadaveric renal allografts. The bioavailability of Aza was low and highly variable (range 5.1‐23.7%). The maximum plasma peak concentration of 6‐MP after an i.v. dose of Aza was 17% of the maximum plasma Aza concentration, but after oral intake the peak concentrations of Aza and 6‐MP were in the same range (38±50 ng/ml and 38±45 ng/ml, respectively). The time to peak, peak concentrations, clearance and elimination half‐life varied widely between patients. It is concluded that the pharmacokinetics of Aza showed remarkably large interindividual variability. Therefore, it is possible that the immunosuppressive potency of Aza would be improved if the drug were dosed according to the individual pharmacokinetics rather than according to the standardized dosing schedules currently used in organ transplantation.
Supraventricular bradycardia following heart transplantation necessitating pacemaker implantation – An analysis of possible underlying causes
Authors: Schmid Christof , Wahlers Thorsten , Jurmann Michael , Cremer Jochen , Fieguth Hans‐Gerd , Schäfers Hans‐Joachim , Haverich Axel
Published: September 2024

Underlying causes for the development of supraventricular bradycardias following heart transplantation are still controversial. A retrospective study investigating preoperative antiarrhythmic drug treatment of the recipient, donor age, ischemic time and surgical complications as possible underlying causes was therefore conducted. From January 1987 through December 1990, 224 orthotopic heart transplantations were performed. After exclusion of redo‐procedures and early deaths, 171 patients (148 male, 23 female; 9 to 62 years, mean 44± 12 yr) were included. While 34 patients showed a supraventricular bradycardia during the early postoperative period (≤14 days), (incidence of 19.9%/Group I), 137 patients demonstrated normal signs rhythm (Group II). All patients in Group I underwent VVI‐pacemaker implantation after a median time interval of 18 d after the initial operation. By Chi‐square‐test analysis, a significant higher cumulative amount of pretransplant antiarrhythmic drug treatment was found in Group I (p< 0.005). However, subsequent multivariant analysis only identified amiodarone to be of significant influence on postoperative pacemaker requirement (ANOVA/Fisher PLSD, 95% confidence level). In contrast, no significant correlation was found with regard to donor age (Group I vs. Group II: 28.1 ± 18.4 yr vs. 26.8± 17.5 yr), ischemic lime (151 ±45 min vs. 149±35 min) and surgical technique. After a follow‐up period of 6 and 12 months, 16 (9.4%) and 15 patients (8.8%) of Group I, respectively, presented ongoing pacemaker demand, whereas 18 and 19 patients, respectively, regained sufficient supraventricular rhythm. In 2 patients surgical reintervention for lead dislocation after endomyocardial biopsy was necessary. It is concluded that about 20% of patients will develop a supraventricular bradycardia after orthotopic heart transplantation that will require a pacemaker. The underlying causes may involve various mechanisms; however, based on our results, only the cumulative amount of preoperative antiarrhythmic drug treatment or amiodarone alone were found to be of significance. Sinoatrial function recovers spontaneously in 50% of the patients within 6 months postoperatively.
An economic analysis of pancreas transplantation: Costs, insurance coverage, and reimbursement
Authors: Evans Roger W. , Manninen Diane L. , Dong Frederick B.
Published: September 2024

Since 1988 the demand for the pancreas transplantation has continued to increase. This has been accompanied by a growth in the number of centers offering the procedure, and an increase in the number of transplants performed. The National Cooperative Transplantation Study was undertaken to document the costs of all transplants, including pancreas transplantation. Data on transplantation procedure charges, from date of transplant to discharge, were obtained from 66.7% of all pancreas transplantation programs active in 1988. These programs accounted for 72% of all transplants performed that year. Valid sample survey data (no more than 25 transplants per center) were obtained for 133 randomly selected patients. This constituted 54% of all procedures done in the United States in 1988. Detailed data were also collected on sources of payment and amount reimbursed. Due to outlier data, we report statistical medians, rather than means, as our measure of central tendency. The median charge for a pancreas transplant with or without a kidney was $66 917, with a hospital length of stay of 21 days, compared with a kidney transplant alone at $39 625 and a hospital length of stay of 14 days. Total pancreas transplant charges fell between $45 260 and $105 375 for 50% of the cases studied. Half of the patients had a hospital length of stay between 16 and 33 days. Due to the small number of cases available for analysis, it was not meaningful to cross‐classify the data according to various prognostic variables. Fifty percent of the transplants studied were paid for by private insurers, and reimbursement exceeded 80% of billed charges for 50.6% of the cases analyzed. Insurance reimbursement for pancreas transplantation is not uniform, but is favorable for those covered. While the number of procedures performed annually has increased since 1980, with the largest increases occurring since 1988, sustained growth may well be a function of insurance coverage. Many transplant centers are unable to bear the expense of pancreas transplants insurers fail to cover. As a result, access will be a problem for some patients.
Simultaneous PTFE reconstruction of the external iliac artery with kidney transplantation
Authors: Schweitzer Eugene J. , Bartlett Stephen T.
Published: September 2024

Four cases of simultaneous reconstruction of the external iliac artery with PTFE (polytetrafluoroethylene) during kidney transplantation are described. The procedure facilitated renal artery anastomosis in these cases where direct anastomosis to the external iliac artery was deemed precarious because of marked atherosclerosis. All the kidneys functioned immediately, and there were no infectious or other complications encountered relative to PTFE placement. It is suggested that simultaneous iliac artery reconstruction with PTFE be considered when the renal artery anastomosis is complicated by severe iliac atherosclerosis.
Psychological adjustment of liver transplant candidates
Authors: Rodrigue James R. , Davis Gary L. , Howard Richard J. , Brunson Matthew E. , Langham Max R. , Haiman Sandra , Behen Joseph
Published: September 2024

The psychological functioning of 20 adult liver transplant candidates was evaluated. Using standardized assessment instruments, we found few personality disturbances and normal levels of anger. However, clinically significant levels of depression and anxiety were reported for 28% and 37% of the sample, respectively. Moreover, patients whose coping strategies were characterized by avoiding the exigencies of their illness reported more depression, more anxiety, and increased psychopathology. Disease severity was also positively correlated with anxiety and avoidant coping strategies. Implications of these findings for the pre‐transplant psychological evaluation are discussed.
Ten‐year experience in the use of double balloon catheter for kidney procurement from non‐heart beating donors in cadaveric kidney transplantation
Authors: Yokoyama Itsuo , Uchida Kazuharu , Tominaga Yoshihlro , Asano Hiroshi , Orihara Akira , Takagi Hiroshi
Published: September 2024

One‐hundred‐and‐twenty patients underwent first cadaveric kidney transplantation from the non‐heart beating donors. All of the organs were procured with the use of double balloon catheter for in situ cooling. The mean warm ischemic time and cold ischemic time were 10.7± 17.0 minutes and 18.9 ± 11.4 hours, respectively. One‐ and 5‐year graft survival rates were 85.0 and 72.7%, respectively. Among 120 recipients, 30 (25%) grafts functioned immediately (immediate function), 82 (68.3%) grafts functioned after varying length of oliguric periods (delayed function) and 8 (6.7%) grafts never functioned (non–function). The mean age of the donors in the group of immediate function (31.5±16.1 yr) was significantly lower than those of other two groups. The mean warm ischemic time in the group of immediate function (6.0± 11.2 min) was significantly shorter than that of delayed function. However, there was no significant difference in donor hypotensive episode, types of preservation fluid and cold ischemic time between the groups. The conclusion is that the ultimate result of cadaveric kidney transplant from the non‐heart beating donors with the use of double lumen catheter is acceptable despite a relatively high incidence of delayed graft function.
Physicians attitudes toward living non‐related renal transplantation (LNRRT)
Authors:   The Living non‐Related Renal Transplant Study Group, Qunibi Wajeh
Published: September 2024

Renal transplantation is considered now the definitive treatment for patients with end‐stage renal disease (ESRD). Unfortunately, the worldwide shortage of kidneys remains the most important obstacle to transplantation. In developing countries, including those of the Middle East, the shortage is even more dramatic. Despite great efforts to establish and maintain successful transplant centers, the number of kidneys that have been transplanted in the last few years has actually declined. The lack of a dependable kidney source played well into the hands of unscrupulous entrepreneurs who started brokerage of organs for profit. In this practice, patients with ESRD travel to India and other countries to purchase kidneys from living genetically non‐related poor donors. Patient care was therefore relegated to the laws of the marketplace and both patients and donors were exploited to maximize profit. Additionally, reported results of this type of transplantation were inferior to those of other types of transplantation. Not unexpectedly, these issues have created intense controversy among transplant physicians and the general public in which moral, ethical and medical issues were debated. To investigate these issues, we conducted a large multicenter study in Saudi Arabia, Bahrain and Egypt. In the first phase of this study, we surveyed 50 institutions regarding their attitude toward LNRRT, of which 22 responded. The results of our survey clearly show that patients with ESRD take the initiative in seeking LNRRT despite physician discouragement and significant financial burden. The transplants were performed expeditiously and patients were sent back to their home countries within a short period of time. Seventy five percent of centers thought that the medical report that was sent with patients was poor or only fair. Responding centers feel that patient education is inadequate, and their compliance with medications and follow‐up visits are poor or only fair. More than half of the centers thought that LNRRT is associated with high mortality. Importantly, 52% of centers reluctantly have come to accept this type of transplantation but thought it should be regulated. All centers suggested that more should be done to improve public education about this type of transplantation. The public should be convinced that expansion of local cadaveric renal transplantation programs would eliminate the need for commerce in human organs.
Questionable benefit of prophylactic acyclovir in renal transplant recipients at high risk for cytomegalovirus disease
Authors: Chitwood Kerrl K. , Heim‐Duthoy Karen L. , Ney Arthur L. , Kasiske Bertram L.
Published: September 2024

Prophylactic acyclovir may help to prevent or ameliorate cytomegalovirus (CMV) disease in high‐risk renal transplant recipients who are CMV‐seronegative pre‐transplant and receive a kidney from a CMV‐seropositive donor. We evaluated the efficacy of prophylactic acyclovir by comparing the incidence and severity of CMV disease in high‐risk acyclovir‐treated patients (n = 28) with that of historical controls (n = 21). Acyclovir was administered for 12.0 ±4.9 weeks (800 to 3200 mg/day p.o. with dose adjusted for renal function). Patients and controls did not differ with respect to age, sex, the number of AB and DR major histocompatibility mismatches, panel‐reactive antibody status, or diabetes. Clinical CMV disease (fever with positive blood culture/antigen or fourfold rise in antibody titer) developed in 50% of acyclovir‐treated patients and in 71% of controls (p = 0.13). When adjustment was made for possible differences between acyclovir patients and controls using logistic regression, the effects of acyclovir on CMV disease were not statistically significant. The severity of CMV disease measured by the duration of fever, days of hospitalization, white blood count nadir, and changes in hepatic enzymes were similar between the groups. These results suggest that acyclovir had little effect on the incidence and severity of CMV disease in these high‐risk renal transplant recipients, and that additional randomized controlled trials are needed to define the role of acyclovir prophylaxis.
OKT3 for induction of immunosuppression in renal transplantation
Authors: Abramowicz Daniel , Goldman Michel
Published: September 2024

A review of the literature on the use of OKT3 for induction of immunosuppression indicates that this drug presents distinct advantages in renal transplantation. In clinical trials comparing OKT3 to cyclosporine in triple‐drug regimens including azathioprine and steroids, OKT3 was associated with a significantly lower number of rejection episodes per patient, a longer time to rejection, and a trend toward improved graft survival. In addition, several high‐risk recipient subgroups experienced significant and clinically meaningful improvement (5% to 10%) in 1‐year graft survival with induction regimens that included OKT3 or ALG as compared to conventional therapy. These subgroups included retransplanted, sensitized, and diabetic patients, as well as those with delayed graft function or HLA‐DR mismatches. In the majority of clinical trials of quadruple‐therapy induction, OKT3 or polyclonal antilymphocyte antibodies in conjunction with azathioprine, steroids, and cyclosporine led to similar graft survival and numbers of patients with rejection episodes. The frequency of infection, however, varied considerably from study to study, and differences between treatments were not consistent. Although OKT3 antibodies have been reported to occur in 3% to 45% of adult patients after an initial course (10 to 14 days) of therapy, successful re‐use of OKT3 has been demonstrated in patients with low antibody titers. Experience with OKT3 for induction of immunosuppression in renal allograft recipients confirms its efficacy in this role.
Treatment and prevention of liver allograft rejection with OKT3
Authors: Höckerstedt Krister
Published: September 2024

Over the past several years, OKT3 therapy has compared well with existing regimens in the treatment and prevention of acute hepatic allograft rejection. When used as first‐line treatment for rejection, OKT3 was shown to be as effective as corticosteroids in reversing the rejection process, particularly in adults. As second‐line therapy for acute rejection, preceded in most studies with only one or two boluses of corticosteroids, OKT3 appeared effective in reversing the clinical picture of rejection. In two of three randomized controlled studies, OKT3 induction therapy with azathioprine and steroids preserved renal function during the first 14 days after transplantation and was associated with significantly fewer acute rejection episodes than was cyclosporine in standard triple‐drug therapy. Adverse reactions following OKT3 administration are similar to those reported in renal allograft recipients and are largely mild and well‐tolerated although a few patients may experience anaphylactic reactions that hamper further OKT3 use. Whether OKT3 induction or rescue therapy increases the risk of infection when compared to other immunosuppressants remains the subject of continued investigation. Some studies associate OKT3 induction with a higher incidence of major infection than that observed with OKT3 rescue therapy. CMV infection prophylaxis is advisable in patients receiving OKT3. OKT3 therapy seems particularly suitable in liver transplant patients with: 1) hepatorenal syndrome; 2) posttransplantation renal insufficiency; 3) acute cyclosporine toxicity; and 4) steroid‐resistant acute rejection.
The use of OKT3 in recipients of pancreatic, pulmonary, and bone marrow allografts
Authors: Peters Hans‐Dieter
Published: September 2024

None of the standard immunosuppressive regimens has proved entirely satisfactory in transplantation of the pancreas, lung, or bone marrow. Comparably high levels of pancreatic graft survival and patient survival have been demonstrated in three trials of quadruple‐drug inductive therapy with either OKT3 or polyclonal antibodies for combined kidney/ pancreas transplants. The overall incidence of infections was similar in both groups. OKT3 has also demonstrated effectiveness in both first‐line and rescue reversal of pancreatic rejections including those resistant to other anti‐lymphocytic agents. Results for early rejection and for combined kidney/ pancreas transplants were superior to outcomes in cases of late rejection and pancreas‐only transplants. Although some reports of lung transplantation with OKT3 for induction show favorable findings, successful immunosuppression with antilymphocytic agents often is hindered by the development of opportunistic infections, particularly cytomegalovirus (CM V). Moreover, these agents have not regularly prevented the appearance of rejection. As it does in pancreatic allografts, OKT3 may rescue transplanted lungs undergoing rejection unresponsive to other agents. In allogenic bone marrow transplants (BMT), OKT3 has been tested variously to prevent or treat graft‐vs‐host disease (GvHD) as well as host‐vs‐graft reactions. The effectiveness of OKT3 in vivo for induction of immune tolerance in BMT is as yet unclear because few patients have been treated. OKT3 has shown considerable promise when used with complement ex vivo to cleanse donor marrow of T lymphocytes prior to transplantation. Furthermore, studies on the treatment of GvHD with OKT3 show an 80% response rate. However, the immunostimulatory effects of OKT3 may exacerbate certain problems common in patients with GvHD.
Optimal use of ciclosporin (Sandimmun®) in liver transplantation: A review of principles and practices
Authors: Bismuth Henri
Published: September 2024

The impact of the immunosuppressive agent ciclosporin on the field of liver transplantation is reviewed and practical considerations for the use of this drug in clinical practice are discussed. One‐year patient survival rates for liver transplant recipients treated with ciclosporin have more than doubled those achieved in the pre‐ciclosporin era. A substantial increase in 5‐year graft survival rates has also been demonstrated (50.4% ciclosporin v.v. 19.4% azathioprine). The pharmacokinetics of ciclosporin is variable and may be particularly inconsistent in patients who have undergone liver transplantation. Blood level monitoring is important to confirm that patients are receiving appropriate doses of ciclosporin and to minimize drug‐related side effects. Surveys of transplant centers in North America have shown the recommended ciclosporin trough levels for liver transplant recipients to range from 80 to 400 ng/ml (whole blood HPLC or mAb‐RIA). Optimal immunosuppressive protocols are still evolving and vary among centers. Immunosuppressive protocols that employ ciclosporin may permit steroid dose reduction or steroid withdrawal in some patients. Combined experience has shown that the side effects associated with ciclosporin therapy such as hypertension, mild‐to‐moderate renal dysfunction and hepatic dysfunction are manageable. Neurological symptoms occur in 25% of liver transplant recipients and may be due in part to the underlying disease.
Living‐related liver transplantation for biliary atresia
Authors: Fujita Shiro , Tanaka Koichi , Tokunaga Yukihiko , Uemoto Shinji , Sano Kaoru , Manaka Dai , Shirahase Isao , Shinohara Hisashi , Yamaoka Yoshio , Ozawa Kazue
Published: September 2024

We reviewed our initial experience of 29 living‐related liver transplantations (LRLT) for children with biliary atresia in terms of postoperative complications and management to analyze the factors that may influence the outcome. All patients underwent an initial portoenterostomy at 17–134 days of age. The age distribution at the time of LRLT ranged from 6 months to 12 years, following revised portoenterostomy 0 to 3 times, and with (n = 5) or without enteric stoma (n = 24). Living‐related donors provided the partial liver grafts weighing 170 to 630 g according to recipient size. Twenty‐six of the 29 recipients are alive and well with follow‐up between 1 and 27 (mean = 14) months. Three patients died of extrahepatic complications including aspiration asphyxia. Candida infection and lymphoproliferative disorder. Four of 5 children with enteric stoma had 9 incidences of postoperative complication, while only 4 incidences occurred in 4 out of 24 children without stoma (p=0.007). Children hospitalized at the time of transplantation seemed to have early postoperative complications more frequently than home‐bound children (p=0.06). The present results indicated that LRLT could offer satisfactory outcome for children in whom repealed Kasai's operation could not attain adequate biliary diversion and for those who developed cirrhosis despite good initial bile drainage. LRLT is not only a promising modality to rescue children with biliary atresia in countries where brain death donors are unavailable but also offers the advantage of optimal timing of surgery for these children at various ages, since it is independent of cadaver graft availability in any region of the world.
Inferior vena cava obstruction after orthotopic liver transplantation
Authors: Brouwers Mark A. M. , de Jong Koert P. , Peeters Paul M. J. G. , Bijleveld Charles M. A. , Klompmaker Ids J. , Slooff Maarten J. H.
Published: September 2024

Post‐operative inferior vena cava (IVC) obstruction is reported as an uncommon complication after orthotopic liver transplantation (OLT). We report 6 cases after 245 OLT's in the period between March ‘79 and December ‘92. Compression or torsion of the IVC or a technical problem were underlying causes. Oligo‐anuria was observed in almost all patients and was probably caused by renal vein hypertension. Doppler ultrasound has become an important tool for the diagnosis of this complication. Operative treatment was performed in almost all cases in order to correct causative factors. Thrombi above or at the level of the upper anastomosis of the IVC should be removed via the right atrium, during cardio‐pulmonary bypass, in order to prevent pulmonary embolism. Thrombi in the IVC caudal to the liver can be removed by cavotomy with high positive end expiratory pressure ventilation.
Early clinical and histologic viability of human liver‐small intestinal allografts after implantation
Authors: Casavilla F. A. , Selby R. , Abu‐Elmagd K. , Reyes J. , Nakamura K. , Wright H. I. , Tzakis A. , Todo S. , Demetris A. J. , Fung J. J. , Van Thiel D. H. , Starzl T. E.
Published: September 2024

Our procedure for donor harvesting and preserving intestinal grafts has matured. In 27 consecutive cases, a protocol was established whose essentials consist of (a) selecting hemodynamically stable donors, (b) antibiotic pretreatment of the donor, and (c) short warm ischemic times (<40 minutes). Assessment of graft quality can be achieved by daily inspection of stomas, inspection for diarrhea >2.5 1/day in adults or >300 ml in children, and weekly protocol or clinically directed endoscopic biopsies. Edema and microscopic separation of the mucosal surface and sloughing are routinely found during the first few posl‐engraftment days, but the crypt cells remain and regenerate a normal mucosa within a week. Recovery of a normal mucosal surface look place in all cases.
Role of 99mTc‐labeled disida scan in the assessment of marginal liver grafts after orthotopic transplantation
Authors: Karademir S. , Csete M. E. , Jurim O. , Finstad T. , Hawkins R. , Bussuttil R. W. , Shaked A.
Published: September 2024

Accurate prognostic indicators are lacking for livers with early marginal graft function, making the decision to re‐transplant a difficult one. Therefore, we studied 99mTc‐labeled DISIDA scanning as a predictor of recovery of marginal grafts. Records of 28 liver transplant recipients with prolonged periods of marginal graft function after liver transplantation were analyzed. Twelve of 28 (Group I) had delayed PNF and were re‐transplanted within 3‐8 days (mean 5.3) of surgery. The remaining 16 (Group II) recovered slowly, with normal graft function at 1 month. All patients received DISIDA scans 2 to 5 d after surgery. Clearance of tracer from the blood pool was slower in Group I patients (77S ± 241 sec) than in Group II (260 ±38 sec; p<0.01). Qualitative differences in the pattern of parenchymal uptake were also noted. Homogenous uptake, consistent with cholestasis, was seen in 15/16 (94%) Group II patients, with improved uptake after 7‐35 d. In contrast, 11/12 Group I patients had nonhomogenous uptake, consistent with multiple liver infarctions. This pattern correlated with higher peak SGOT in Group I (4358 ± 658 U/dl vs. 1636±127 U/dl p<0.01), and PT (20±0.7 sec vs. 16.5±0.36 sec; p<0.01). In summary, delays in DISIDA tracer clearance from blood, and non‐homogenous hepatic uptake correlate with elevated liver function tests and with delayed PNF. Homogenous uptake correlates with graft recovery. DISIDA scans may, therefore, be useful in predicting recovery of marginal grafted livers.
Orthotopic liver transplantation for familial amyloidotic polyneuropathy
Authors: Lewis W. David , Skinner Martha , Simms Robert W. , Jones Lee Anna , Cohen Alan S. , Jenkins Roger L.
Published: September 2024

Orthotopic liver transplantation for inborn errors of metabolism has become a standard indication for transplantation in pediatric and adult patients with alpha‐1 antitrypsin deficiency, Wilson's disease and tyrosinemia, amongst several less common diseases. Familal amyloidotic polyneuropathy (FAP) is a rare autosomal dominant disease whose metabolic origin lies in an abnormal protein synthesized primarily in the liver. FAP, also discussed as the autosomal dominant form of amyloidosis, is characterized as a hereditary form of amyloidosis. It is the rarest form of amyloidosis affecting kindreds of specific ethnic backgrounds. The true incidence of this disease in the United States is not known. The mutant protein, called transthyretin or prealbumin, forms amyloid fibrils which accumulate in vital tissues ultimately leading to the patient's death. Liver transplantation for this inherited disease leads to the production of normal transthyretin protein. This theoretically should arrest the disease process. The first 5 patients in the United States with FAP who have undergone transplantation are presented.