Outcomes of “one‐day” vs “two‐day” injection protocols using Tc‐99m tilmanocept for sentinel lymph node biopsy in breast cancer

No prior studies have compared Tc‐99m tilmanocept (TcTM) one‐day and two‐day injection protocols for sentinel lymph node (SLN) biopsy in breast cancer (BC). We retrospectively identified patients with clinically node‐negative BC undergoing SLN biopsy at our institution. Patients received a single, intradermal peritumoral injection of TcTM on day of surgery or day prior to surgery in addition to an intraoperative injection of isosulfan blue dye. Univariable and multivariable Poisson regression count models were constructed to assess the effects of injection timing, radiologist, patient and surgeon characteristics on the number of removed SLNs. A total of 617 patients underwent SLN biopsy with TcTM and blue dye. Sixty‐seven (10.9%) patients were injected with the two‐day protocol. Patients in the one‐day protocol had a mean of 3.0 (standard deviation (SD) 1.9) SLNs removed compared with 2.7 (SD 1.4) SLNs in the two‐day protocol, P‐value = .13. On multivariable analysis, patient age and operating surgeon significantly affected the number of removed SLNs; however, the injection timing and the nuclear radiologist did not influence the number of removed SLNs. The performance of Tc‐99m tilmanocept did not differ significantly between one‐day and two‐day injection protocols. These results are similar to other radiotracers used for SLN biopsy in BC.     

Routine surveillance endoscopy and biopsy after isolated intestinal transplantation—Revisiting the gold standard

The value of endoscopy and biopsy after intestinal transplantation in the absence of clinical concerns has never been investigated. We examined clinical yield of routine surveillance endoscopy and biopsy (control group, n = 28, Jan 2011 to Jun 2014). Most episodes of acute rejection were diagnosed when there were clinical symptoms or signs such as increased stoma output, fever, or bacteremia, but not by routine surveillance endoscopy and biopsy. The new protocol abandoned routine surveillance. Intestinal allografts were examined only when relevant clinical symptoms and/or signs raised concern for graft dysfunction. We compared outcomes between control and study groups (new protocol, n = 25, Jul 2014 to Dec 2016). Incidence of acute rejection (32% vs 32%), graft salvage rate after acute rejection treatment (78% vs 63%), patient survival (75% vs 88% 1 year, 71% vs 83% 3 years after intestinal transplantation), and graft survival (68% vs 80% 1 year, 61% vs 76% 3 years after intestinal transplantation) were similar between control and study groups. Protocol‐driven, routine surveillance endoscopy, and biopsy do not appear to confer any survival advantage to patients or grafts. Endoscopy and biopsy “for cause” without routine surveillance seem to be effective and adequate to monitor intestinal allografts.     

Isolated vascular “v” lesions in liver allografts: How to approach this unusual finding

According to the Banff criteria for kidney allografts, isolated vascular or “v” lesions are defined as intimal inflammation, age‐inappropriate fibro‐intimal hyperplasia, or both, without the presence of associated interstitial T cell‐mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the “v” lesions are identified in patients with coexistent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified nine patients at a mean of 1805 days posttransplantation and compared these to matched controls. Almost half (4 of 9) of the study patient biopsies showed inflammatory arteritis associated with focal or diffuse C4d positivity, which was not observed in matched controls. One “v” lesion patient progressed to rejection‐related graft failure and two developed moderate/severe TCMR in subsequent biopsies, whereas only one rejection episode occurred in follow‐up biopsies, and no rejection‐related deaths or graft failures were detected in controls. In conclusion, patients with liver allograft isolated “v” lesions should undergo further evaluation and closer follow‐up for impending TCMR and/or underlying co‐existent chronic antibody‐mediated rejection (AMR).     

Treatment of Steroid‐Resistant Acute Renal Allograft Rejection With Alemtuzumab

Steroid‐resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid‐resistant renal allograft rejection treated with alemtuzumab (15–30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5‐4.0 mg/kg bodyweight i.v. for 10–14 days; n = 20). We assessed treatment‐failure (graft loss, lack of improvement of graft function or need for additional anti‐rejection treatment), infections during the first 3 months after treatment and infusion‐related side effects. In both groups, the median time‐interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff‐IIA or higher. Three alemtuzumab‐treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion‐related side‐effects in three alemtuzumab‐treated patients (27%), and more severe infusion‐related side effects in 17 RATG‐treated patients (85%, p = 0.013). Drug related costs of alemtuzumab‐treatment were lower than of RATG‐treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid‐resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion‐related side‐effects. These data warrant a prospective trial.     

Alemtuzumab dose adjusted for body weight is associated with earlier lymphocyte repletion and less infective episodes in the first year post renal transplantation – a retrospective study

The optimal dose of alemtuzumab for renal transplant induction is not known, and the doses reported in the literature vary. This study compares two separate dosing regimens of alemtuzumab in renal transplantation. The first is a standard fixed dose of 30 mg (SD), and the second is a dose adjusted for body weight at 0.4 mg/kg (AD). In this first year post‐transplant, there was no difference in patient [HR 0.64 (0.22–1.86), P = 0.39] or allograft survival [HR 1.18 (0.48–2.90), P = 0.72] between the two groups. There was also no difference in overall rejection‐free survival [HR 1.12 (0.79–1.58), P = 0.53]. However, absolute lymphocyte count was significantly higher at all measured time points in the first year in the AD group. There were also less episodes of urosepsis [HR 1.38 (1.03–1.85), P = 0.037] and fungal infection [HR 5.15 (2.00–13.28), P = 0.015] in the AD group compared with the SD group. This study shows that AD alemtuzumab is associated with earlier lymphocyte repletion and less infective episodes in the first year postrenal transplant, without increasing the risk of rejection. This work highlights the need for studies into the optimal dosing of monoclonal antibodies used in transplantation.     

Intensive glycemic control after heart transplantation is safe and effective for diabetic and non‐diabetic patients

Some studies have shown increased mortality, infection, and rejection rates among diabetic (DM) compared to non‐diabetic (non‐DM) patients undergoing heart transplant (HT). This is a retrospective chart review of adult patients (DM, n = 26; non‐DM, n = 66) undergoing HT between June 1, 2005, and July 31, 2009. Glycemic control used intravenous (IV) and subcutaneous (SQ) insulin protocols with a glucose target of 80–110 mg/dL. There were no significant differences between DM and non‐DM patients in mean glucose levels on the IV and SQ insulin protocols. Severe hypoglycemia (glucose <40 mg/dL) did not occur on the IV protocol and was experienced by only 3 non‐DM patients on the SQ protocol. Moderate hypoglycemia (glucose >40 and <60 mg/dL) occurred in 17 (19%) patients on the IV protocol and 24 (27%) on the SQ protocol. There were no significant differences between DM and non‐DM patients within 30 d of surgery in all‐cause mortality, treated HT rejection episodes, reoperation, prolonged ventilation, 30‐d readmissions, ICU readmission, number of ICU hours, hospitalization days after HT, or infections. This study demonstrates that DM and non‐DM patients can achieve excellent glycemic control post‐HT with IV and SQ insulin protocols with similar surgical outcomes and low hypoglycemia rates.     

Alemtuzumab with Rapid Steroid Taper in Simultaneous Kidney and Pancreas Transplantation: Comparison to Induction with Antithymocyte Globulin

We compared our experience with alemtuzumab induction and rapid steroid taper (RST) in simultaneous kidney and pancreas transplantation (SKPT) with a historic control group who received rabbit antithymocyte globulin (r-ATG) induction with RST. 74 SKPTs performed at our center between January 2005 to November 2008 who underwent immunosuppression with RST in combination with r-ATG induction (n = 33; 1.5 mg/kg × 4 for a total dose of 6 mg/kg) or alemtuzumab induction (n = 41; 30 mg single dose). Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil. Steroids were discontinued after postoperative day 4. Recipient and transplant characteristics were similar between the 2 groups, with 82% of the r-ATG and 80% of the alemtuzumab group steroid free at 1 year. The rate of clinical acute rejection episodes was 12% in the r-ATG group and 15% in the alemtuzumab group. The rates of cytomegalovirus (CMV) infection, BK nephropathy, and graft survival were similar between the 2 groups. There was no difference in mean serum creatinine, calculated GFR, or fasting blood sugar at 1 year between the 2 groups, whereas glycosylated hemoglobin (HbA1c) was lower at 1 year in the alemtuzumab (5.3 ± 0.4) versus the r-ATG group (5.6 ± 0.4; P = .0021). Induction with r-ATG or alemtuzumab with RST was safe and effective in SKPT. The incidences of acute rejection episodes, CMV infection, and BK nephropathy were similar. Mean HbA1C at 1 year was lower among the alemtuzumab group. Further long-term follow-up is needed to confirm these results.     

Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection

Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 ± 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT‐AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX‐AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8–12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT‐AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection.     

When patients fail UNAIDS’ last 90 ‐ the “failure cascade” beyond 90‐90‐90 in rural Lesotho,Southern Africa: a prospective cohort study

Introduction : HIV‐infected individuals on first‐line antiretroviral therapy (ART) in resource‐limited settings who do not achieve the last “90” (viral suppression) enter a complex care cascade: enhanced adherence counselling (EAC), repetition of viral load (VL) and switch to second‐line ART aiming to achieve resuppression. This study describes the “failure cascade” in patients in Lesotho. Methods : Patients aged ≥16 years on first‐line ART at 10 facilities in rural Lesotho received a first‐time VL in June 2014. Those with VL ≥80 copies/mL were included in a cohort. The care cascade was assessed at four points: attendance of EAC, result of follow‐up VL after EAC, switch to second‐line in case of sustained unsuppressed VL and outcome 18 months after the initial unsuppressed VL. Multivariate logistic regression was used to assess predictors of being retained in care with viral resuppression at follow‐up. Results : Out of 1563 patients who underwent first‐time VL, 138 (8.8%) had unsuppressed VL in June 2014. Out of these, 124 (90%) attended EAC and 116 (84%) had follow‐up VL (4 died, 2 transferred out, 11 lost, 5 switched to second‐line before follow‐up VL). Among the 116 with follow‐up VL, 36 (31%) achieved resuppression. Out of the 80 with sustained unsuppressed VL, 58 were switched to second‐line, the remaining continued first line. At 18 months’ follow‐up in December 2015, out of the initially 138 with unsuppressed VL, 56 (41%) were in care and virally suppressed, 37 (27%) were in care with unsuppressed VL and the remaining 45 (33%) were lost, dead, transferred to another clinic or without documented VL. Achieving viral resuppression after EAC (adjusted odds ratio (aOR): 5.02; 95% confidence interval: 1.14–22.09; p = 0.033) and being switched to second‐line in case of sustained viremia after EAC (aOR: 7.17; 1.90–27.04; p = 0.004) were associated with being retained in care and virally suppressed at 18 months of follow‐up. Age, gender, education, time on ART and level of VL were not associated. Conclusions : In this study in rural Lesotho, outcomes along the “failure cascade” were poor. To improve outcomes in this vulnerable patient group who fails the last “90”, programmes need to focus on timely EAC and switch to second line for cases with continuous viremia despite EAC.     

Beyond 10 years,with or without an intestinal graft: Present and future?

Long‐term outcomes in children undergoing intestinal transplantation remain unclear. Seventy‐one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10‐year posttransplant outcomes with (group 1, n = 26) and without (group 2, n = 9) a functional graft. Ten‐year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87 mL/min/1.73 m². Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10 years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3‐drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.     

Comparison of alemtuzumab vs. antithymocyte globulin induction therapy in primary non‐sensitized renal transplant patients treated with rapid steroid withdrawal

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single‐center, cohort study evaluated cumulative incidence of one‐yr biopsy‐proven acute rejection (BPAR) among 200 consecutive primary non‐sensitized kidney transplant recipients who received either alemtuzumab (n = 100) or rATG (n = 100) induction followed by rapid steroid taper, tacrolimus, and mycophenolate mofetil. Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate glomerular filtration rate (iGFR), were obtained at 1, 4, and 12 months from transplantation. The one‐yr BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, p = 0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2–10.5, p = 0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, p = 0.046). One‐year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 mL/min/1.73 m², p = 0.002) and three‐yr graft survival (89.5% vs. 95%, p = 0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid‐free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.     

Adipose‐derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long‐term graft tolerance in vascularized composite allotransplantation

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation‐free conditioning protocol that combines anti‐lymphocyte serum (ALS), tacrolimus, and cytotoxic T‐lymphocyte‐associated protein 4 immunoglobulin (CTLA4‐Ig) with adipose‐derived stromal cells (ASCs) to allow VCA survival without long‐term systemic immunosuppression. Full‐mismatched rat hind‐limb‐transplant recipients received tacrolimus (0.5 mg/kg) for 14 days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC‐group received CTLA4‐Ig (10 mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1 × 10⁶ iv, POD 2, 4, 7, 15, 28); the ASC‐cyclophosphamide (CYP)‐group received CTLA4‐Ig, ASC plus cyclophosphamide (50 mg/kg ip, POD 3); the ASC‐ALS‐group received CTLA4‐Ig, ASCs plus ALS (500 µL ip, POD 1, 5). Banff grade III or 120 days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection‐free VCA survival was 28 days in CTRL (n = 7), 34 in ASC (n = 6), and 27.5 in ASC‐CYP (n = 4). In contrast, ASC‐ALS achieved significantly longer, rejection‐free VCA survival in 6/7 animals (86%), with persistent mixed donor‐cell chimerism, and elevated systemic and allograft skin T_regs, with no signs of acute cellular rejection. Taken together, a regimen comprised of short‐course tacrolimus, repeated CTLA4‐Ig and ASC administration, combined with ALS, promotes long‐term VCA survival without chronic immunosuppression.     

Strategic breakthrough in adult ABO‐incompatible living donor liver transplantation: preliminary results of consecutive seven cases

ABO‐incompatibility is a major obstacle to expanding exiguous donor pools in adult liver transplantation, especially in countries where grafts from deceased donors are uncommon. We present our preliminary results of ABO‐incompatible (ABO‐I) adult living donor liver transplantation (LDLT) using a new, simple protocol. Seven consecutive cases of ABO‐I LDLT were managed by the same protocol including pre‐operative administration of a single dose of rituximab (375 mg/m²) followed by three to five sessions of plasma exchange before LDLT without portal infusion therapy. The triple immunosuppression protocol consisted of tacrolimus, mycophenolate mofetil and steroids, with mycophenolate mofetil starting seven d before LDLT. Splenectomy was performed for all cases. All patients are alive (100% survival) with a mean follow‐up of 852 d (715–990 d). Neither antibody‐mediated nor hyperacute rejection were encountered. There was only one episode of mild acute cellular rejection, for which steroid augmentation was effective. The median preformed isoagglutinin antibody titer before plasma exchange was 256, while the median antibody titer immediately before LDLT was 16. In conclusion, adult ABO‐I LDLT results were excellent – comparable or even superior to those of ABO‐compatible LDLT. ABO‐I adult LDLT has now become a more applicable modality without the need for an appropriate donor.     

Campath,calcineurin inhibitor reduction,and chronic allograft nephropathy (the 3C Study) – results of a randomized controlled clinical trial

Calcineurin inhibitors (CNIs, eg, tacrolimus) reduce short‐term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg, sirolimus) pathway might avoid long‐term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial of sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6 months posttransplantation. The primary outcome of this analysis was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomization; 197 patients were assigned sirolimus‐based and 197 to tacrolimus‐based therapy. Allocation to sirolimus had no significant effect on eGFR at 18 months: baseline‐adjusted mean (SEM) eGFR was 53.7 (0.9) mL/min/1.73 m² in the sirolimus group versus 54.6 (0.9) mL/min/1.73 m² in the tacrolimus group (P = .50). Biopsy‐proven acute rejection (29 [14.7%]) vs 6 [3.0%]; P < .001) and serious infections (defined as opportunistic infections or those requiring hospitalization; 95 [48.2%] vs 70 [35.5%]; P = .008) were more common among participants allocated sirolimus. Compared with tacrolimus‐based therapy, sirolimus‐based maintenance therapy did not improve transplant function at 18 months after conversion and was associated with significant hazards of rejection and infection. ClinicalTrials.gov identifier NCT01120028 and ISRCTN88894088.     

“Turn downs” in aortic emergencies: Reassurance or uncertainty?

“Turn‐down” rate has been reported to have a significant influence on outcomes, and being turned down for an operation is associated with significant short‐term mortality risk. A study examining the impact of the pandemic on the “turn‐down” rates of acute aortic syndromes in the United Kingdom reported an overall “turn‐down” rate of  7.3% in the early part of the pandemic. This review examines the significance of “turn‐downs” in this setting and scrutinizes the adequacy of reporting this complex variable.     

Preemptive treatment of early donor‐specific antibodies with IgA‐ and IgM‐enriched intravenous human immunoglobulins in lung transplantation

This retrospective study presents our 4‐year experience of preemptive treatment of early anti‐HLA donor specific antibodies with IgA‐ and IgM‐enriched immunoglobulins. We compared outcomes between patients with antibodies and treatment (case patients) and patients without antibodies (control patients). Records of patients transplanted at our institution between March 2013 and November 2017 were reviewed. The treatment protocol included one single 2 g/kg immunoglobulin infusion followed by successive 0.5 g/kg infusions for a maximum of 6 months, usually combined with a single dose of anti‐CD20 antibody and, in case of clinical rejection or positive crossmatch, with plasmapheresis or immunoabsorption. Among the 598 transplanted patients, 128 (21%) patients formed the case group and 452 (76%) the control group. In 116 (91%) patients who completed treatment, 106 (91%) showed no antibodies at treatment end. Fourteen (13%) patients showed antibody recurrence thereafter. In case versus control patients and at 4‐year follow‐up, respectively, graft survival (%) was 79 versus 81 (P = .59), freedom (%) from biopsy‐confirmed rejection 57 versus 53 (P = .34), and from chronic lung allograft dysfunction 82 versus 78 (P = .83). After lung transplantation, patients with early donor‐specific antibodies and treated with IgA‐ and IgM‐enriched immunoglobulins had 4‐year graft survival similar to patients without antibodies and showed high antibody clearance.     

Vascularized composite tissue allotransplantation – state of the art

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including – but not limited to – trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short‐ and long‐term outcomes have been excellent, thus far. Acute rejections are common in the early post‐operative period, and immunosuppression‐related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long‐term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA‐specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.     

Continuous function of 80 primary renal allografts for 30–47 years with maintenance prednisone and azathioprine/mycophenolate mofetil therapy: A clinical mosaic of long‐term successes

Eighty primary renal allograft recipients, 61 living‐related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30–47 years. They were treated with three different early immunosuppression programs (1963–1970: thymectomy, splenectomy, high oral prednisone; 1971–1979: divided‐dose intravenous methylprednisolone; and 1980–1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long‐term treatment often included the anti‐platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40‐year success. At 35 years, death‐censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan–Meier estimate). Biopsy‐documented early acute cellular and highly probable antibody‐mediated rejections were reversed with divided‐dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non‐plasma‐cell malignancies was identified. Twenty‐seven azathioprine‐treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a “low immunosuppression state of allograft acceptance (LISAA)”. The lifetime achievements of these patients following a single renal allograft and low‐dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.     

Alemtuzumab Induction and Antibody-Mediated Rejection in Kidney Transplantation

BackgroundInduction therapy improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the incidences of antibody-mediated rejection (AMR) and acute cellular rejection (ACR) as well as graft and patient outcomes in KTRs who underwent induction with alemtuzumab versus rabbit-antithymocyte globulin (r-ATG).MethodsThis was a single-center retrospective study involving patients who underwent kidney transplantation between January 2009 and December 2011 after receiving induction therapy with either alemtuzumab or r-ATG. Maintenance immunosuppression included tacrolimus and mycophenolate mofetil with early steroid withdrawal. Acute rejection was diagnosed using allograft biopsy.ResultsAmong the 108 study patients, 68 received alemtuzumab and 40 got r-ATG. There was a significantly higher incidence of AMR (15% vs 2.5%; P = .008) and similar incidence of ACR (4.4% vs 10%; P = .69) for alemtuzumab versus r-ATG groups. One-year serum creatinine levels (l.68 ± 0.8 mg/dL vs 1.79 ± 1.8 mg/dL; P = .66) as well as graft (91.1 ± 3.5% vs 94.5 ± 3.8%; P = .48) and patient (93.8 ± 3.0% vs 96.4 ± 3.5%; P = .92) survivals were similar for the alemtuzumab versus the r-ATG groups.ConclusionOur study showed a higher incidence of AMR and similar incidence of ACR in KTRs who underwent induction with alemtuzumab compared with those who received r-ATG and were maintained on tacrolimus and MMF. This was despite a lower HLA mismatch in the alemtuzumab group. One-year graft survival, patient survival, and allograft function were similar. Inadequate B-cell suppression by alemtuzumab as well as altered phenotypic and functional properties of repopulating B cells could be contributing to heightened risk of AMR in these patients.     

A prospective “test‐and‐treat” demonstration project among people who inject drugs in Vietnam

Introduction

Modelling suggests that early diagnosis and immediate antiretroviral therapy (ART) among key populations would have a substantial impact in reducing HIV transmission and mortality in Vietnam. An implementation research project of “test‐and‐treat” among people who inject drugs (PWID) was developed to inform effective roll‐out of such interventions.

Methods

“Test‐and‐treat” was offered to PWID in two high burden provinces, Thai Nguyen and Thanh Hoa. The interventions comprised the offer of biannual HIV testing and immediate ART, irrespective of CD4 count. PWID were enrolled between April 2014 and July 2015 and followed up for 12 months, and retention, HIV viral load (VL) and risk behaviours were assessed. Retention in care of this prospective cohort was compared with the retention among men enrolled in care in the preceding period (April 2012 to March 2013) at the same clinics when ART was initiated at CD4 cell count ≤350 cells/mm³.

Results

In total, 287 HIV positive PWID started immediate ART. The majority (98%) were men; median age was 34; and median (interquartile range) CD4 count was 199 (50 to 402) cells/mm³. After 12 months, 238 participants (83%) were retained on ART, and 205 achieved viral suppression (<1000 copies/mL) (92% among those in whom VL was measured, 71% overall). Baseline CD4 count ≤100 cells/mm³ and history of imprisonment were associated with lower retention and viral suppression, while engagement in methadone maintenance was associated with higher retention. Retention in care was higher in the “test‐and‐treat” cohort (83%) compared with men enrolled in care in the preceding period (78%), primarily because lost‐to‐follow‐up during pre‐ART care was eliminated. No decline in consistent condom use and clean needle use was observed.

Conclusions

Early ART initiation resulted in successful treatment outcomes among PWID, with no observed increase in self‐reported risk behaviours, suggesting feasibility and potential effectiveness of “test‐and‐treat” approach. The results also call for differentiated care for PWID, including promoting early diagnosis and engagement in methadone maintenance therapy while enhancing care for those with advanced HIV disease and history of imprisonment.