scholarly journals Absence of Rejection in a Facial Allograft Recipient with a Positive Flow Crossmatch 24 Months after Induction with Rabbit Anti-Thymocyte Globulin and Anti-CD20 Monoclonal Antibody

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Bruce E. Gelb ◽  
J. Rodrigo Diaz-Siso ◽  
Natalie M. Plana ◽  
Adam Jacoby ◽  
William J. Rifkin ◽  
...  

Background. Donor-specific antibodies (DSA) to human leukocyte antigen increase the risk of accelerated rejection and allograft damage and reduce the likelihood of successful transplantation. Patients with full-thickness facial burns may benefit from facial allotransplantation. However, they are at a high risk of developing DSA due to standard features of their acute care. Case Presentation. A 41-year-old male with severe disfigurement from facial burns consented to facial allotransplantation in 2014; panel reactive antibody score was 0%. In August of 2015, a suitable donor was found. Complement-dependent cytotoxicity crossmatch was negative; flow cytometry crossmatch was positive to donor B cells. An induction immunosuppression strategy consisting of rabbit antithymocyte globulin, rituximab, tacrolimus, mycophenolate mofetil (MMF), and methylprednisolone taper was designed. Total face, scalp, eyelid, ears, and skeletal subunit allotransplantation was performed without operative, immunological, or infectious complications. Maintenance immunosuppression consists of tacrolimus, MMF, and prednisone. As of posttransplant month 24, the patient has not developed acute rejection or metabolic or infectious complications. Conclusions. To our knowledge, this is the first report of targeted B cell agents used for induction immunosuppression in skin-containing vascularized composite tissue allotransplantation. A cautious approach is warranted, but early results are promising for reconstructive transplant candidates given the exceptionally high rate of acute rejection episodes, particularly in the first year, in this patient population.

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Cremona ◽  
J Garlasco ◽  
I Gintoli ◽  
A D'Ambrosio ◽  
F Quattrocolo ◽  
...  

Abstract Background Antibiotics (AB) are administered for medical prophylaxis (MP) to prevent infectious complications. The second national point prevalence survey (PPS) of healthcare-associated infections and AB use was conducted in Italy in 2016-2017. The survey found MP accounted for nearly 25% of all registered ABs, more than twice the EU/EEA proportion. The aim of this study was to evaluate how many ABs were administered for MP and how frequently general indications were followed. Methods Data from the PPS were used to evaluate the prevalence of indications for MP over the total number of ABs, the proportion - among these indications - of those justified by a motivation in the patients' charts, and the prevalence of ABs considered appropriate for MP. The evaluation was made in 12 hospitals out of 14 participating in the PPS in Piedmont, chosen on the basis of patient traceability. According to national guidelines, the indications for MP that were considered appropriate in this study were: Trimethoprim/sulfamethoxazole for P. carinii pneumonia, Rifaximin for diverticulitis, Penicillin for Streptococcal infections and for splenectomized patients, and Rifampin for TB infections. Results 1844 AB prescriptions were registered among 1334 traceable inpatients in Piedmont. The prevalence of indications for MP was 16.2% and 253 ABs (84.6%) were prescribed with a motivation. Only 3% of ABs registered as MP were appropriate for this indication: Bactrim 2%, Rifaximin 0.3%, Penicillin 0.2% and Rifampin 0.4%. Conclusions This study found an extremely high rate of inappropriate ABs for MP, that will be further investigated through qualitative analysis of medical records to evaluate whether a misunderstanding of the PPS protocol occurred and empirical therapy was confused with MP. Nevertheless, this study highlighted the need for interventions to improve prescribing appropriateness for MP. Key messages This study found that only 2.98% of ABs registered as MP among traceable patients in Piedmont were appropriate for this indication. 15.38% of prescriptions for MP were not justified by a motivation. Interventions to improve prescribing appropriateness for MP could lead to a considerable reduction in inappropriate use of ABs, which is crucial in a country facing hyperendemic levels of AMR.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S349-S349 ◽  
Author(s):  
Hanine El Haddad ◽  
George Viola ◽  
Ying Jiang ◽  
Issam Raad ◽  
Kenneth V Rolston ◽  
...  

Abstract Background Percutaneous nephrostomy tubes (PCN) are indicated for relief of urinary tract obstruction. These devices are prone to mechanical and infectious complications. The infection rate at 90 days is ±20%. Our objective was to determine whether discordant antimicrobial coverage provided prior to PCN exchange was associated with a higher rate of recurrent infection compared with those who received concordant therapy. Methods We retrospectively reviewed 780 patients that had undergone initial PCN placement at our institution between July 2014 and February 2017. We only included patients that had developed a definite PCN infection, subsequent PCN exchange, with a minimum 30 day post-PCN exchange follow up. We defined PCN infection as the presence of a positive urine culture (≥104 cfu/mL) plus symptoms consistent with a urinary tract infection. Recurrence was defined as a new PCN infection with the isolation of the same organism to the initial episode. Antibiotics were defined as concordant if they had activity against all organisms’ isolated based on antimicrobial susceptibilities. Results A total of 47 patients met our inclusion criteria. The median age of patients was 59, with 49% being male. The most common underlying tumors were urothelial (45%), cervical (17%) and prostate cancer (15%). Clinical characteristics included ureteral stents (17%), diabetes (19%), history of GU surgery (38%), and active chemotherapy at the time of PCN insertion (70%). The median time to onset of infection was 42 days. Infections were polymicrobial in 50% of the cases. The most common organisms encountered were Pseudomonas spp. (36%), Enterococcus spp. (23%) and Escherichia coli (18%). The median length of follow up of PCN tubes after exchange was 55 days. There were 12 (26%) recurrences occurring at a median time of 27 days. The provision of discordant antibiotics preceding PCN exchange was significantly associated with recurrence of infection (66.7% vs. 12.8%; P < 0.002). Conclusion Discordant antimicrobial therapy provided during PCN exchange, in the setting of a PCN infection is associated with a higher rate of relapse. Therefore, to decrease the high rate for PCN reinfection, we propose that prior to PCN exchange secondary to infection, patients should be receiving concordant antimicrobial therapy. Disclosures All authors: No reported disclosures.


2021 ◽  
Author(s):  
Astha Thakkar ◽  
Jesus Gonzalez Lugo ◽  
Niyati Goradia ◽  
Radhika Gali ◽  
Lauren C. Shapiro ◽  
...  

As COVID-19 has been shown to adversely affect patients with cancer, prophylactic strategies are critically needed. We determined the immunogenicity of COVID-19 vaccination in a cohort of cancer patients that had received full dosing with one of the FDA-approved COVID-19 vaccines. 201 oncology patients underwent anti-spike protein SARS-CoV-2 IgG testing post-vaccination and demonstrated a high rate of seroconversion (94%) overall. When compared to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients of anti-CD20 therapies (70%) and stem cell transplantation (74%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were noted following vaccination with the adenoviral when compared to the mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify vulnerable cohorts that need novel vaccination or passive immunization strategies.


1999 ◽  
Vol 10 (8) ◽  
pp. 1806-1814
Author(s):  
SHANE M. MEEHAN ◽  
CHRISTOPHER T. SIEGEL ◽  
ANDREW J. ARONSON ◽  
SHARON M. BARTOSH ◽  
J. RICHARD THISTLETHWAITE ◽  
...  

Abstract. The relationship of borderline infiltrates to acute rejection by Banff criteria in renal allografts of patients receiving only maintenance immunosuppression is not clear. Renal allograft biopsies with borderline lesions that were not treated with additional anti-rejection therapy were retrospectively studied. Sixty-five such biopsies were identified from 50 patients, and their outcome was determined by serum creatinine and/or histologic findings in subsequent biopsies, up to 40 d after the initial biopsy. In addition to the borderline infiltrates, there was evidence of acute cyclosporine or tacrolimus toxicity (58%), acute tubular necrosis (12%), and urinary obstruction (12%). Forty-day follow-up after 30 (46%) biopsies revealed serum creatinine <110% of baseline, and repeat biopsies were not indicated. In 17 (26%), the serum creatinine initially decreased, then increased, and follow-up biopsies showed acute rejection in nine. In 18 (28%), the creatinine remained elevated and follow-up biopsies revealed acute rejection in nine. The untreated borderline infiltrates were thus nonprogressive after 47 biopsies (72%) and progressed to histologic acute rejection after 18 (28%). When there was increasing or persistently elevated creatinine after the initial biopsy, 51% of cases (18 of 35) progressed to acute rejection. Infiltrates that progressed to rejection had more frequent glomerulitis (7 of 18 versus 3 of 47, P = 0.003) and Banff acute score indices (i+t+v+g) >2 (16 of 18 versus 29 of 47, P = 0.03). A majority (72%) of borderline infiltrates not given additional anti-rejection therapy did not progress to acute rejection over 40 d of follow-up, suggesting that conservative management of these lesions, at least in the short term, may be more appropriate than routine treatment as acute rejection.


2013 ◽  
Author(s):  
Jamil Azzi ◽  
Belinda T. Lee ◽  
Anil Chandraker

Half a century after the first successful kidney transplantation, we still stand at the crossroads of immunology and transplantation, where science meets art in the management of complex end-stage renal disease (ESRD) patients. Successful transplantation requires not only a lifetime’s commitment from patients but also a multidisciplinary approach, bringing together surgeons, transplant nephrologists, primary care physicians, scientists, and nurses to provide coordinated care. Although transplantation is the treatment of choice for the vast majority of ESRD patients, many patients remain on dialysis due to a relative imbalance between demand for and supply of suitable organs. This chapter provides a comprehensive overview of recipient evaluation and immunosuppression. Risk factors that prohibit transplantation are discussed, as are human leukocyte antigen/ABO compatibility, transplant immunobiology, induction therapy, maintenance therapy, transplantation for special populations, and future directions in the field. Tables outline Amsterdam Living Donation Forum guidelines, ABO blood group compatibilities, and pretransplant immunologic testing. Visual aids include graphs, charts, cell illustrations, and an evaluative algorithm. This chapter contains 10 figures, 3 tables, 101 references, and 5 Board-styled MCQs.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ahmed Abo omar ◽  
Gamal Saadi

Abstract Background and Aims Transplantation is the first successful modality of renal replacement therapy (RRT) for irreversible chronic kidney disease (CKD; stage 5). Identifying additional factors associated with poor long-term prognosis after transplantation may provide clues regarding the pathophysiological mechanisms involved in allograft failure and identify high-risk patients who may benefit from additional monitoring or interventions. Successful kidney transplantation results in a substantial decrease in β2M levels, but a delayed decrease or increasing levels after transplantation may serve as a marker of acute rejection or inflammation. Several reports show that elevated sCD30 levels, pre and post transplantation are associated with a poor prognosis for long term kidney graft survival. These studies found higher CD30 levels in allograft recipients and a good predictor of impending acute rejection. The aim of the work is to study the prognostic outcomes of transplanted kidney using CD30 and β2-Microglobulin Method prospective study was conducted in nephrology unit –internal medicine department at Tanta and Kasr El Ainy university ,over 1 year.20 patients subjected to primary Tx.participated in this study.Cd30 and β2M.at day -1,2weeks and 3 months,with clinical follow up after 1 year to detect graft survival Results At day -1,level of cd30 was higher in rejection group than the other patient group.2 weeks post transplantation ,level of cd30 was higher in rejection group than the other patient group and at 3 monthes post transplantation level of cd30 was higher in rejection group than the other patient group,and these differences are statistically highly significant.(p values :0.003 ,0.005 and 0.002 respectively) Successful transplantation leads to significant decrease in serum cd30 at 2 weeks post tx.(P1 &lt;0.005) and at 3 monthes post tx. (P1&lt;0.001) although in rejection group, significant decrease in cd30 was at 2 weeks post tx.only(P1&lt;0.005) and at 3 monthes serum cd30 began to rise again with( P1 0.157). At day -1,level of β2microglobulin was higher in rejection group than the other patient groupwith statistically significant difference (p. 0.01).2 weeks post transplantation ,level of β2microglobulin was higher in rejection group than the other patient groupbut statistically not significant(p. 0.18 ) and at 3 monthes post transplantation level of β2microglobulin was higher in rejection group than the other patient group but statistically non significant(p. 0.18 ). Successful transplantation leads to significant decrease in serum β2microglobulin at 2 weeks post tx.(P1 &lt;0.002) and at 3 monthes post tx. (P1&lt;0.001) although in rejection group ,significant decrease in β2microglobulin was at 3 monthes post tx.only(P1&lt;0.005) and at 2 weeks no significant decrease(p1 0.15) Conclusion pre transplantation high Cd30 and β2M is associated with poor outcome.failure of decrease of cd30 and β2M post Tx. also associated with poor outcome or infection. Successful transplantation leads to significant decrease in serum cd30 and β2M. which can be used as predictors of graft survival with better sensitivity and specificity than serum creatinin.


2020 ◽  
Vol 9 (12) ◽  
pp. 3986
Author(s):  
Sinem Ünlü ◽  
Nils Lachmann ◽  
Maximilian Jara ◽  
Paul Viktor Ritschl ◽  
Leke Wiering ◽  
...  

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.


2018 ◽  
Vol 39 (02) ◽  
pp. 117-125 ◽  
Author(s):  
Christian Merlo ◽  
Jonathan Orens

AbstractLung transplantation is a widely accepted treatment to manage the advanced stages of many lung diseases that have failed to respond to all other therapeutic interventions. There have been ever-expanding indications for lung transplantation as a treatment for lung disease. The International Society for Heart and Lung Transplantation (ISHLT) updated guidelines for candidate selection in 2014. This document was published to serve as a guide in selecting appropriate candidates for lung transplantation. Ideal candidates for lung transplantation are those with near-end stage disease, limited life expectancy due to their lung disease, and who experience significant loss in quality of life. At the same time, candidates should be free of significant comorbidities that might negatively impact successful transplantation. Despite well thought out published guidelines for candidate selection, many controversial issues surrounding selection of lung transplant candidates remain. This review will focus on some of the more common controversial issues and explain how most centers approach these issues when choosing candidates for lung transplantation.


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