***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The incidence of  posttransplant diabetes mellitus ( PTDM ) was compared in three groups of renal transplant recipients : nondiabetic patients who had been r and omized between 1980 and 1983 to receive antilymphoblast globulin ( ALG ) , azathioprine ( AZA ) , and prednisone ( P )  ( group 1 ) or cyclosporine ( CsA ) plus prednisone ( group 2 ) . Group 3 consisted of a more recent ( 1984 - 85 ) cohort who were given a combination of azathioprine , cyclosporine , and prednisone ( + /- ALG ) .  PTDM developed in 20 of 173 previously nondiabetic 18 - 55-year-old patients . Three of 47 patients ( 6.4 % ) in group 1 , 4 of 58 patients ( 6.9 % ) in group 2 , and 13 of 68 patients in group 3 ( 19.1 % ) developed PTDM . Thus in the two groups composing the concurrent prospect i ve r and omized trial ( groups 1 and 2 ) the incidence of PTDM did not differ . The subsequent patients who were given a combination of ALG , azathioprine , cyclosporine , and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2 . PTDM usually occurred within two months of transplantation , and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin . The incidence of PTDM was not significantly affected by sex of the recipient , HLA-type , primary renal disease , rejection episodes , primary vs. secondary transplant , or prior splenectomy . The incidence of PTDM is greater in patients older than 45 ( 34.2 % vs. 5.2 % ) , and heavier than 70 kg ( 21.1 % vs. 5.1 % ) ; in recipients of cadaveric allografts ( 15.7 % vs. 4.6 % ) ; and in patients who were hospitalized for infections ( 22.4 % vs. 4.7 % ) . CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic . One-year actuarial patient survival in those with PTDM was 83.3 % vs. 98 % ( P less than .01 ) in the nondiabetic and graft survival was 77.1 % vs. 87.1 % ( NS ) . The combination of Minnesota ALG , azathioprine , cyclosporine , and prednisone appears to predispose older , heavier recipients of cadaver allografts to the development of PTDM . The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression BACKGROUND The addition of induction therapy with antilymphocytic antibodies to cyclosporine ( CsA ) based immunosuppression , has reduced acute rejection incidence and improved short-term survivals , but has not had well-established effects on long-term renal transplant survival . PATIENTS We analyzed the long-term allograft outcome of patients included in a prospect i ve r and omized clinical study conducted in our center 15 years ago by comparing two strategies : ( A ) horse antilymphoblast globulin ( ALG ) given at 10 mg/kg on alternate days to a maximum of 6 doses with low-dose CsA started at 8 mg/kg per day and prednisone at 0.25 mg/kg per day , versus ( B ) CsA started at 15 mg/kg per day and prednisone at 0.5 mg/kg per day . Diabetic and highly sensitized patients ( PRA > 70 % ) were excluded from the study . RESULTS The characteristics of the 50 patients enrolled in each group were not different . Although patient survival was not different ( 88 % in group A vs 77 % in group B ) , recipients treated with ALG showed a lower incidence of acute rejection episodes ( 20 % vs 44 % , P = .01 ) and better death-censored renal allograft survival ( 57 % vs 41 % , P = .03 ) . Among rejection-free patients , graft survival was 15 % higher in group A ( 60 % vs 45 % , P = .12 ) . Multivariate Cox regression analysis showed that an acute rejection episode ( relative risk [ RR ] : 2.44 , 95 % confidence interval [ CI ] 1.36 - 4.39 ; P = .0029 ) rather than ALG immunosuppression ( RR 0.74 , 95 % CI 0.41 - 1.33 ; P = NS ) was an independent predictor of death-censored graft survival . CONCLUSIONS In summary , we confirmed that concomitant induction therapy with ALG , CsA , and steroids improves long-term renal allograft survival Background . New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocol s that emphasize reduction or avoidance of steroids and calcineurin inhibitors . Methods . In a r and omized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors , group A received  Thymoglobulin  , group B received Alemtuzumab , and group C received Daclizumab . Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms , and methylprednisolone in groups A and C only ( st and ard clinical institutional practice ) . The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C , respectively , with a targeted mycophenolate dose of 1 g twice daily . However , in group B , the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity , with 500 mg twice-daily doses of mycophenolate , without steroid maintenance . Results . In this 15-month median postoperative interval report , there were no notable differences in demographics and patient and graft survivals . Acute rejection rates at 1 year were equivalent , that is , 5 of 30 in all three groups ( 16.6 % ) . In group B , there was slightly lower renal function at 1 month , but no difference at 1 year . There was also significantly more leukopenia , but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis , respectively , in group B. Conclusions . This preliminary analysis indicates that 80 % of the patients in group B remained steroid-free 1 year postoperatively , with lower tacrolimus trough levels and no difference in other adverse events Background Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs . Data on their in vivo effects on T- and B-cell phenotype and function are limited . Methods In a r and omized double-blind placebo-controlled study to prevent renal allograft rejection , patients were treated with tacrolimus , mycophenolate mofetil ( MMF ) , steroids , and a single dose of rituximab or placebo during transplant surgery . In a subset of patients , we analyzed the number and phenotype of peripheral T and B cells by multiparameter flow cytometry before transplantation , and at 3 , 6 , 12 , and 24 months after transplantation . Results In patients treated with tacrolimus/MMF/steroids  the proportion of central memory CD4 + and CD8 + T cells was higher at 3 months post-transplant compared to pre-transplant levels . In addition , the ratio between the percentage of central memory CD4 + and CD4 + regulatory T cells was significantly higher up to 24 months post-transplant compared to pre-transplant levels . Interestingly , treatment with tacrolimus/MMF/steroids result ed in a shift toward a more memory-like B-cell phenotype post-transplant . Addition of a single dose of rituximab result ed in a long-lasting B-cell depletion . At 12 months post-transplant , the small fraction of repopulated B cells consisted of a high percentage of transitional B cells . Rituximab treatment had no effect on the T-cell phenotype and function post-transplant . Conclusions Renal transplant recipients treated with tacrolimus/MMF/steroids  show an altered memory T and B-cell compartment post-transplant . Additional B-cell depletion by rituximab leads to a relative increase of transitional and memory-like B cells , without affecting T-cell phenotype and function . Trial Registration Clinical Trials.gov In renal transplantation , IL-17 production by T-cells might be dependent on the presence of B-cells . Therefore , the effect of in vivo B-cell depletion on ex-vivo IL-17 production was investigated . Twenty patients undergoing living-donor renal transplantation were recruited from a larger cohort of patients participating in a r and omized , double-blind trial . All patients were allocated to a single intra-operative dose of either placebo or rituximab ( 375 mg/m(2 ) ) added to the st and ard immunosuppressive therapy . Blood was collected at baseline , at one day , and at one month after surgery . The healthy kidney donors also gave blood at baseline . Peripheral blood mononuclear cells were stimulated ex-vivo in different manners ( heat killed C and ida albicans yeast , heat killed Staphylococcus aureus , or αCD3αCD28 coated beads ) , to address the role of B-cells in ex-vivo cytokine responses . The concentration of monocyte- and T-cell-derived cytokines ( IL-1β , IL-6 , TNF-α , IFN-γ , IL-17 and IL-22 ) was measured in supernatants . Of the 20 recruited patients , 13 received treatment with rituximab and 7 received placebo . In all patients , IL-17 was produced by CD4-positive , γδTCR-negative cells . After stimulation , there was no difference between patients and healthy controls in ex-vivo production of IL-17 or other cytokines . In all patients there was a general decrease of monocyte- and T-cell-derived cytokines after transplantation , except for IL-17 . There was no difference between patients who received rituximab and patients who received placebo . A single dose of rituximab treatment added to st and ard immunosuppressive therapy in renal transplant patients did not influence the production of IL-17 or other monocyte- or T-cell derived cytokines after ex-vivo stimulation UNLABELLED The use of the antilymphoblast globulin ( ALG ) or OKT3 associated with cyclosporine ( CyA ) and steroids has been useful in kidney cadaveric transplantation . 101 patients who received their first cadaveric renal transplant were r and omized according to the immunosuppression used . Group A ( n = 53 ) : horse ALG 15 mg/kg just before transplant surgery ; ALG 12 mg/kg on the first day after transplant followed by 4 doses of 10 mg/kg on alternate days ; Cya p.o 8 mg/kg/d ; prednisone 0.25 mg/kg/d . Group B ( n = 48 ) : OKT3 5 mg just before transplant followed by 4 doses of 5 mg/d . ; CyA and prednisone were administered using the same schedule as group A. RESULTS the incidence of rejection during the first 3 months was : group A : 13 percent , group B : 17 percent ( NS ) . The probability of being free of acute rejection ( Kaplan-Meier ) 24 months after transplant was 89 percent in group A and 79 percent in group B ( NS ) . The day of onset of the first acute rejection episode was 25 + /- 20 days after transplant in group A , and 17 + /- 10 day in group B ( NS ) . Incidence of tubular necrosis : group A 21 percent , group B 19 percent ( NS ) Rabbit antithymocyte globulin ( rATG ; Thymoglobulin ( ® ) ) is currently used to prevent acute rejection in kidney transplantation . The dose and regimen of rATG have not been optimized . Moreover , the impact of different treatment regimens on T-cell phenotype reconstitution remains unknown . We conducted a prospect i ve r and omized study of 17 renal transplant patients to determine the pharmacokinetics of total and active ( bound to human cells ) rATG and T-cell phenotype reconstitution after rATG administration . Patients received rATG  at a total dose of 6mg/kg , administered either as 1.5mg/kg/day on days 0 - 3 ( Group 1 , n=8 ) or 3mg/kg on days 0 and 3 ( Group 2 , n=9 ) . All patients received tacrolimus , mycophenolate mofetil and steroids .  Blood sample s were assayed for total rATG by enzyme linked immunosorbent assay and active rATG by flow cytometry . Maximum concentrations and terminal half-lives were similar between the two groups but at month 3 Group 1 had significantly lower values for total rATG ( concentration was 6.2±1.1μg/mL versus 10.2±2.9μg/mL in Group 2 , p=0.027 ) and total rATG  dose-normalized A 
    Output:
    
The effect of alemtuzumab with steroid minimisation on NODAT was uncertain , compared to ATG with steroid maintenance .
Treatment effects were uncertain for NODAT , thrombocytopenia , and malignancy or PTLD.Rituximab had uncertain effects on death , graft loss , acute rejection and all other adverse outcomes compared to placebo .
AUTHORS ' CONCLUSIONS ATG reduces acute rejection but has uncertain effects on death , graft survival , malignancy and NODAT , and increases CMV infection , thrombocytopenia and leucopenia .
Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection , assuming a 21 % rejection risk with ATG.Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented .
Overall , ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient-centred outcomes ( reduced death or lower toxicity ) do not appear to be improved