Organ Transplant Patients Research Articles

Mortality and Cardiovascular Outcomes in Adult Non-Liver Solid Organ Transplant Patients With Nonalcoholic Steatohepatitis

The effect of nonalcoholic steatohepatitis (NASH) on mortality or major adverse cardiovascular events (MACE) in non-liver solid organ transplant recipients (NL-SOT) is unknown. Using a retrospective design, adult NL-SOT recipients who had biopsy-proven NASH were compared NL-SOT recipients with normal liver function tests and imaging; propensity matched at a 1:10 ratio on the following: age, sex, race, transplant year, transplant organ, smoking status, and diabetes status. Both deceased and living donor recipients were included; heart and liver transplant patients were excluded. Primary outcome was incidence of all-cause mortality and MACE (a composite outcome of coronary artery disease, ischemic stroke, and peripheral arterial disease). Seven patients (3 kidney and 4 lung transplants) had biopsy-proven NASH and 70 patients without NASH, both groups were predominantly male (53%-57%), White (86%-91%), and overweight (mean body mass index ∼ 26). The majority of patients were on calcineurin inhibitors (≥85%), antimetabolites (≥97%), and prednisone (≥50%). Survival analysis showed that NASH patients had a higher risk of death (hazard ratio [HR], 3.24; 95% confidence interval [CI], 1.26-8.33, P=0.02). NASH did not affect the risk of death-censored graft failure (HR, 1.08; 95% CI, 0.14-8.67; P=.94) or the risk of MACE (HR, 1.03; 95% CI, 0.23-4.62; P=.97). In NL-SOT recipients, NASH is significantly associated with mortality but not with MACE.

Malnutrition in solid organ transplant patients: A review of the literature.

Screening for malnutrition is of vital importance for solid organ transplant candidates to optimize nutrition status before transplant, to improve clinical outcomes and to inform selection committees of nutritional contraindications and risks. There are multiple criteria and screening tools available for determining malnutrition diagnosis and risk. Registered Dietitian Nutritionists use these tools for nutrition assessments to quantify the severity of malnutrition, provide patient-centered interventions, and monitor progression. Many transplant centers in the United States utilize the American Society of Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics' Adult Malnutrition Criteria, though there is limited research using these criteria specifically in the transplant population. Malnutrition, utilizing other diagnostic and screening tools, has been associated with important complications, including longer length of hospital stay, increased mortality, decreased quality of life, worsened end-stage organ progression, and decreased functional status. Malnutrition typically results from sarcopenia and cachexia, and can ultimately lead to frailty, causing further negative impacts on transplant outcomes. This literature review summarizes the current research on malnutrition in solid organ transplant candidates and provides recommendations for future research and current practice implications.

Successful Remission of Refractory Plantar Warts with Cantharidin Plus in an Immunosuppressed Patient

Organ transplant patients on immunosuppressive therapies are susceptible to developing refractory human papillomavirus (HPV) infections including cutaneous warts. These warts are known to respond to conservative treatment modalities in the immunocompetent but are often refractory to multiple treatments in the immunosuppressed. Here we report a case of an immunosuppressed adult with plantar warts recalcitrant to numerous therapies that was ultimately treated successfully with cantharidin-podophyllotoxin-salicylic acid (CPS) monotherapy. After 19 treatment sessions over a 16-month time period, complete resolution was achieved. CPS may be a promising treatment modality in cases of severe, refractory verruca plantaris such as those seen in our immunosuppressed patient.

Extra-urogenital infection by Mycoplasma hominis in transplant patients: two case reports and literature review

BackgroundMycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients.Case PresentationWe hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection.ConclusionsThe prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients.

Considering Innovative Clinical Care for Organ Transplant Patients With Advanced Cutaneous Head and Neck Malignancies.

Considering Innovative Clinical Care for Organ Transplant Patients With Advanced Cutaneous Head and Neck Malignancies.

Toxic effects of sirolimus and everolimus on the development and behavior of zebrafish embryos

Sirolimus and everolimus have been widely used in children. These mammalian target of rapamycin (mTOR) inhibitors have shown excellent efficacy not only in organ transplant patients as immunosuppressive agents but also in patients with some other diseases. However, whether mTOR inhibitors can affect the growth and development of children is of great concern. In this study, using zebrafish models, we discovered that sirolimus and everolimus could slow the development of zebrafish, affecting indicators such as survival, hatching, deformities, body length, and movement. In addition to these basic indicators, sirolimus and everolimus had certain slowing effects on the growth and development of the nervous system, blood vessels, and the immune system. These effects were dose dependent. When the drug concentration reached or exceeded 0.5 μM, the impacts of sirolimus and everolimus were very significant. More interestingly, the impact was transient. Over time, the various manifestations of experimental embryos gradually approached those of control embryos. We also compared the effects of sirolimus and everolimus on zebrafish, and we revealed that there was no significant difference between these drugs in terms of their effects. In summary, the dose of sirolimus and everolimus in children should be strictly controlled, and the drug concentration should be monitored over time. Otherwise, drug overdosing may have a certain impact on the growth and development of children.

Epidemiology of cytomegalovirus antiviral resistance testing for solid organ and bone marrow transplant patients from 2011 - 2019.

CMV reactivation post-transplantation is common, with need for prompt identification of patients most at-risk for CMV antiviral drug resistance (AVDR). This study describes CMV AVDR frequencies, antiviral prescribing practices, and AVDR risk factors in patients from 2011 to 2019 in British Columbia, Canada. Retrospective review of demographics, transplant type, viral loads, antiviral exposure duration, and 12-month mortality was conducted for all patients with samples submitted for CMV AVDR testing from 2011 to 2019. Genotyping of AVDR mutations occurred at the national reference laboratory. Mann-Whitney U, T-test or Fisher's exact tests examined differences between patients with and without AVDR. Fifty-three plasma and three tissue/fluid specimens successfully underwent CMV AVDR testing; of these samples, 27/56 (48%) had AVDR mutations detected. The commonest AVDR mutations were at UL97 loci A594 (20%), H596 (12%) and L595 (12%). Mutations occurred more frequently in requests from solid organ than hematopoietic stem cell transplant patients (58% vs. 27%, p=0.05). Previous resistance testing was a significant risk factor for AVDR (p<0.001). Patients with AVDR had approximately 51 more days of antiviral therapy (p=0.007) and took 9 days longer to clear viremia (p=0.23). The median turnaround time from sample send-out to reporting was nine days. However, empiric use of second-line antivirals occurred in most cases (39/53, 74%) before results were available. Laboratories should strive to provide timely CMV AVDR testing for transplant patients, to minimize unnecessary exposure to second-line antiviral agents. The findings of this study may help guide clinicians when selecting empiric antiviral therapy.

43203 Cutaneous squamous cell carcinoma is associated with lower overall survival in solid organ transplant patients: a matched case-control study

43203 Cutaneous squamous cell carcinoma is associated with lower overall survival in solid organ transplant patients: a matched case-control study

Investigating Tacrolimus Disposition in Paediatric Patients with a Physiologically Based Pharmacokinetic Model Incorporating CYP3A4 Ontogeny, Mechanistic Absorption and Red Blood Cell Binding.

Tacrolimus is a crucial immunosuppressant for organ transplant patients, requiring therapeutic drug monitoring due to its variable exposure after oral intake. Physiologically based pharmacokinetic (PBPK) modelling has provided insights into tacrolimus disposition in adults but has limited application in paediatrics. This study investigated age dependency in tacrolimus exposure at the levels of absorption, metabolism, and distribution. Based on the literature data, a PBPK model was developed to predict tacrolimus exposure in adults after intravenous and oral administration. This model was then extrapolated to the paediatric population, using a unique reference dataset of kidney transplant patients. Selecting adequate ontogeny profiles for hepatic and intestinal CYP3A4 appeared critical to using the model in children. The best model performance was achieved by using the Upreti ontogeny in both the liver and intestines. To mechanistically evaluate the impact of absorption on tacrolimus exposure, biorelevant in vitro solubility and dissolution data were obtained. A relatively fast and complete release of tacrolimus from its amorphous formulation was observed when mimicking adult or paediatric dissolution conditions (dose, fluid volume). In both the adult and paediatric PBPK models, the in vitro dissolution profiles could be adequately substituted by diffusion-layer-based dissolution modelling. At the level of distribution, sensitivity analysis suggested that differences in blood plasma partitioning of tacrolimus may contribute to the variability in exposure in paediatric patients.

Difficulties and Needs of Organ Transplantation Patients After Discharge

Organ nakli, cerrahideki ilerlemeler ve immünosüpresif ilaçların gelişmesiyle beraber işlev ve fonksiyonunu yitiren organlar için en etkili tedavi yöntemidir. Ancak organ nakil hastaları ameliyat sonrası evde psikolojik, fizyolojik ve sosyal bazı zorluklar yaşamaktadırlar. Nakilden sonra hastalar yaşamlarının büyük çoğunluğunu evde geçirmektedir. Nakil sonrası hastalar başta psikolojik zorluklar olmak üzere fizyolojik, sosyal ve diğer zorluklar yaşamaktadırlar. Hastaların bu zorluklarla başa çıkması için bazı gereksinimleri oluşmaktadır. Hastalar en fazla psikolojik alanda bir ihtiyaç duymakla beraber eğitim ve bilgi ihtiyacı, sosyal ve diğer ihtiyaçların karşılanma hissi duymaktadırlar. Ayrıca organ nakli hastalarının yaş gruplarına ve cinsiyetlerine göre karşılaşılan zorluklar ve gereksinimleri değişebilmektedir. Bu nedenle organ nakli olan hastaların evde bakımlarının düzenli yapılması ve sosyal desteğin sürdürülmesi hastanın yaşam kalitesini yükseltmesi açısından önemlidir. Hastalara organ nakli sonrası sunulan taburculuk eğitiminin ve sağlanan bilgilerin yeterli ve açık olmadığı görülmektedir. Sağlık profesyonelleri organ nakli sonrası hastaların karşılaşacakları zorluklar ve gereksinimleri önceden belirleyerek hastaya özgü eğitim vermelidir. Ameliyat sonrası hasta ve hasta yakınları ile etkili iletişimin sağlanması, hastaların bu süreci daha kolay atlatması ve yaşam kalitesini yükseltmesi açısından oldukça önemlidir.

The Relationship Between Spiritual Well-Being and Post-Traumatic Growth in Turkish Patients Undergoing Solid Organ Transplantation.

This study was conducted to determine the relationship between spiritual well-being and post-traumatic growth in solid organ transplant patients. This cross-sectional study was conducted with 366 patients who presented to the organ transplantation polyclinic of a university hospital between September 2021 and February 2022 in Turkey. The mean Post-Traumatic Growth Inventory and Spiritual Well-Being Scale scores of solid organ transplant patients were 81.33 ± 20.28 and 37.18 ± 8.69, respectively. There was a significant positive correlation between post-traumatic growth and spiritual well-being. According to linear regression analysis, spiritual well-being, gender, marital status, transplanted organ, donor type, and previous mental disorders were statistically significant predictive factors that affected post-traumatic growth. Spiritual well-being was an important variable that affected post-traumatic growth in solid organ transplant patients. Therefore, healthcare providers can provide individualized psychosocial-spiritual care and counseling services that increase post-traumatic growth in patients after organ transplantation.

The Medical Relevance of Toxoplasma Infections in Terms of the Safety of Blood Recipients under Immunosuppression-A Meta-Analysis.

Laboratory diagnosis of Toxoplasma gondii infection plays a crucial role in ensuring the safety of blood recipients, especially in the case of immunosuppressed people, such as organ transplant patients. Toxoplasmosis, caused by the parasite Toxoplasma gondii, is a potential threat to people with weakened immune systems, and blood transfusions from infected donors can lead to severe complications. In this publication, we analyze the medical relevance of Toxoplasma infection in the context of the safety of blood recipients, focusing on the immunosuppressed patient population. We present various diagnostic methods, such as serological, molecular, and microscopic tests, which can detect the presence of Toxoplasma gondii in donors' blood. We also discuss the importance of adequately interpreting diagnostic results, considering risk factors, and detectability of the infection. We pay special attention to high-sensitivity and -specificity diagnostic techniques, which allow us to minimize the risk of Toxoplasma gondii transmission to blood recipients. Our findings have important implications for clinical practice and organ transplantation guidelines, emphasizing the need to diagnose and monitor Toxoplasma infections in blood donors and recipients.

A scoping review of pediatric transplant education.

Education is crucial for pediatric patients and caregivers throughout the transplant continuum, yet data are lacking around which interventions are effective and in what circumstances. We undertook a scoping review with the objectives of (a) describing the types, effects, and outcomes of patient-focused educational interventions before and after pediatric transplant and (b) understanding the educational experiences of patients and caregivers. Five scientific databases were explored for relevant literature using the JBI methodology. Educational interventions published in English, targeting pediatric solid organ transplant patients (0-25 years) and their caregivers were included. Relevant data from eligible articles (n = 27) were extracted and summarized. Eighteen articles describing 17 educational interventions were identified for objective A, and nine articles qualitatively assessing patient or parental learning needs were identified for objective B. Most interventions were directed toward teenage patients and their caregivers post kidney transplant, primarily focusing on medication self-management and adherence, or providing general information on transplant using multicomponent delivery formats. Most interventions achieved statistically significant improvements in knowledge (n = 8/9) and patients or caregivers expressed satisfaction with the intervention (n = 7/7) but health-related outcomes such as medication adherence (n = 2/6) or behavior change (n = 1/3) rarely achieved statistically significant results. In objective B, patients and caregivers described the transplant process as overwhelming, but indicated that social supports and education helped them cope. Participants consistently wanted more information than they received. Caregivers and pediatric patients value transplant education, but high-quality studies are limited. Since education is a fundamental part of the transplant process, future research in this area should be prioritized.

Mohs micrographic surgery for keratinocyte carcinomas: clinicopathological predictors of the number of stages

Background The number of Mohs stages needed to remove a keratinocyte carcinoma affects resource use, expenses, and repair complexity. This study aimed to identify clinicopathological predictors associated with increased or decreased stages and areas for further research. Methods A retrospective review was conducted from a single private practice with two Mohs surgeons of 2788 consecutive Mohs cases between January 2017 and December 2021, analyzing the average number of stages taken versus national norms (P = 0.21) and subgroups using unpaired t tests (*<0.05). Results Several tumor features were significantly associated with fewer stages: squamous cell carcinomas, Mohs appropriate use criteria score of 7 or 8, preoperative size <0.25 cm2, tumors on the lips and extremities (including hands/fingers), and smoking. Clinicopathological features significantly associated with more stages included Mohs appropriate use criteria score of 9, recurrent skin cancers, basal cell carcinomas, tumor size of 2.25–3.99 cm2, cancers on ears, solid organ transplant patients, treatment delays >180 days, and patients ≥90 years old. Conclusions Significant predictors exist for both increased and decreased numbers of Mohs micrographic surgery stages required to eradicate a tumor, which may help Mohs surgeons facilitate, plan, and allocate resources more effectively. Areas for further research in Mohs micrographic surgery are identified.

The Spectrum of Tigecycline-Induced Pancreatitis in Clinical Characteristics, Diagnosis, and Management.

Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP. Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis. Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9-87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5-61) versus 57.5 years (range 9-87) (P=0.03). The median time of symptom onset was 7 days (range 2-29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1-43), and the median time to relieve symptoms was 4 days (range 1-12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia. Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients.

Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study

Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (n = 150), cases with keratinocyte cancers and tumor-free controls, considering the most important risk factors for keratinocyte cancer in solid organ transplant recipients. Using whole exome data of germline DNA from this patient cohort, we identified several genetic loci associated with the occurrence of multiple keratinocyte cancers. We found one genome-wide significant association of a common single nucleotide polymorphism located in EXOC3 (rs72698504). In addition, we found several variants with a p-value of less than 10−5 associated with the number of keratinocyte cancers. These variants were located in the genes CYB561, WASHC1, PITRM1-AS1, MUC8, ABI3BP, and THBS2-AS1. Using whole exome sequencing data, we performed groupwise tests for rare missense variants in our dataset and found robust associations (p &lt; 10−6, Burden Zeggini test) between MC1R, EPHA8, EPO, MYCT1, ADGRG3, and MGME1 and keratinocyte cancer. Thus, overall, we detected genes involved in pigmentation/UV protection, tumor suppression, immunomodulation, intracellular traffic, and response to UV as genetic risk factors for multiple keratinocyte cancers in solid organ transplant recipients. We also grouped selected genes to pathways and found a selection of genes involved in the “cellular response to UV” to be significantly associated with multiple keratinocyte cancers.

#3176 STUDY OF UNUSUAL/RARE INFECTIONS IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Infections are the most common cause of mortality in solid organ transplant patients. Kidney transplant is the most common organ transplantation worldwide. Since its successful outcomes and longevity of patients, wide literature is available about the long term outcomes and infections. They are more susceptible to infections in the first six months of transplant as per Rubin's calendar when immunosuppression is high. The most common opportunistic infections like Pneumocystis jirovecii, CMV infection, reactivation of tuberculosis, other viral infections like hepatitis B and hepatitis C viruses and fungal infections like Cryptococcus were well studied. There are very few studies on atypical infections about their clinical presentation, anibiogram and outcomes of the patients. Method It is retrospective analysis of clinical presentation, methods of diagnosis, antibiogram, graft's &amp; patient's outcomes of renal allograft recipients with atypical infections. All renal allograft recipients from 2006 to 2021 who had atypical infections were included. The clinical data obtained from hospital data and collected using epidata software and results were analyzed using PSPP software. Results A total of 1498 patients underwent renal transplant in this center during 2006 to 2021. Only 33 patients had unusual/rare infections like nocordosis (12), Rhodococcus (1), Meliodosis (2), Pheohypomycosis (3), Aspergillosis (6), Histoplasmosis (1), and Parvovirus (8). Nocorodiosis occurred after mean duration of 6.3 years after transplant. Most of the patients with nocordiosis, presented with prolonged fever and cutaneous abscesses, culture which grew nocordiosis. They responded to Imipenem and Septran, but few strains were septran resistant for which fluroquinolones were given. Overall the outcomes of graft and Patients were good. The patient with rhodococcus presented with sepsis with MODS and was expired. The patients with pheohyphomycosis presented with cutaneous abscess and responded to prolonged course of Itraconazole with good graft outcome without mortality. Out 6 patients with Aspergillus Pneumonia which developed after 4.6 years after renal transplantation, 3 patients were expired with graft loss. The patients of parvovirus infection presented with refractory post-transplant anemia and evaluation showed pure red cell aplasia on bone marrow studies. Most of them developed within one year of transplant and four of them received anti-rejection therapy. Five patients responded to standard treatment with IV immunoglobulin, but three patients required 2 doses of Inj. Rituximab 500 mg each in view of probable Parvo virus triggered auto immune hemolytic anemia. Conclusion This study focused on the atypical infections like nocordosis, Rhodococcus, Meliodosis,Pheohypomycosis, Aspergillosis, Histoplasmosis, Parvovirus and their antibiogram and outcomes of graft and mortality. The high index of suspicion should be present when patient is not responding to empirical antibiotics and culture didn't grow routine organsims. The role of invasive investigations like bronchoscopy with BAL fluid whoudl be considered whenever the infections like nocordiosis and aspergillus were considered. Transplant with cutaneous abscesses should not be treated with empirical antibiotics and always culuture should be done to rule out infections like nocordiosis, pheohypomycosis and histoplasmosis as treatment is different for each orgaims. Post-transplant refractory anemia requires bone marrow evaluation to look for Parvovirus infection which responds to IVIg. Overall, the high index of suspicion, timely diagnosis, correct drug and duration of treatment will save the graft and patient.

Organ transplant patients in the emergency department

Zusammenfassung Hintergrund Patienten nach solider Organtransplantation stellen in der Notaufnahme ein spezielles Kollektiv dar, wobei atypische Beschwerdebilder sowie komplexe Begleitfaktoren die Behandler vor besondere Herausforderungen stellen. Ziel der Arbeit Charakterisierung von organtransplantierten Patienten in der Notaufnahme im Hinblick auf ihre Leitsymptome bzw. Diagnosen und Unterschiede zwischen den einzelnen Transplantatorganen. Material und Methoden Retrospektive deskriptive Analyse von Patienten nach solider Organtransplantation, die sich innerhalb von 2 Jahren in der Notaufnahme der Medizinischen Hochschule Hannover vorgestellt haben. Ergebnisse Untersucht wurden 977 Vorstellungen organtransplantierter Patienten. Führende Leitsymptome waren Fieber (23,6 %), allgemeine Schwäche (19,2 %) und Bauchschmerzen (17,0 %). Am häufigsten konnte die Diagnose eines akuten Infekts (43,8 %) gestellt werden, gefolgt von der akuten Funktionsverschlechterung des Organtransplantats (19,3 %). In der Subgruppe des akuten Infekts waren bei nierentransplantierten Patienten (NTx) die ableitenden Harnwege, bei lebertransplantierten (LeTx) die Gallenwege und bei lungentransplantierten Patienten (LuTx) die Atemwege der primäre Fokus. In der Subgruppe der Patienten mit akuter Funktionsverschlechterung des Organtransplantats zeigte sich bei NTx-Patienten die infektbedingte Transplantatverschlechterung führend, während bei LeTx- und LuTx-Patienten die akute Abstoßung überwog. Schlussfolgerungen Fieber und akute Schwäche sind häufige, jedoch unspezifische Beschwerdebilder, die zur Vorstellung organtransplantierter Patienten in der Notaufnahme führen. Diesen liegt vielfach eine Infektion oder eine akute Verschlechterung der Transplantatfunktion zugrunde.

Development of a novel UPLC-MS/MS method for the simultaneous quantification of mycophenolic mofetil, mycophenolic acid, and its major metabolites: Application to pharmacokinetic and tissue distribution study in rats

Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) used to prevent rejection in organ transplant patients. The purpose of this study is to develop a sensitive LC-MS/MS method to simultaneously quantify MMF, MPA, and two major metabolites, mycophenolic acid-glucuronide (MPAG) and Acyl-mycophenolic acid-glucuronide (AcMPAG) and applied this method in a pharmacokinetic (PK) and tissue distribution study. A Shimadzu UHPLC system coupled to an AB Sciex QTrap 4000 mass spectrometer was used for the analysis. Protein precipitation with a mixture of methanol: acetonitrile (2:1, v:v) was used to process the plasma samples and tissue samples. Separation was achieved using an Ultra Biphenyl 5 µm column (100 × 2.1 mm) with 0.1% formic acid in water (A) and acetonitrile (B) as the mobile phases. Quantification analysis was performed under positive ionization mode using the multiple reaction monitoring (MRM) approach. The method was linear in the range of 1.22 – 1250.00 nM for all four analytes with correlation coefficient values > 0.99. The method was reproducible, with intra- and inter-day accuracy ranging from 85.0 ± 11.2–108.3 ± 6.50 for all analytes in both plasma, liver and intestine homogenates. The extraction recovery and matrix effect of plasma sample using a mixture methanol/acetonitrile (2:1, V:V) can achieve an acceptable range (<20%), but extraction recovery and matrix effect of AcMPAG decreased to 64.10 ± 15.42 in the liver and intestine homogenates. The analytes in plasma were found to be stable under bench-top, freeze-thaw, and storage conditions. The validated method was successfully applied to quantify MMF, MPA, MPAG, and AcMPAG in a rat PK study. The PK results showed MPA was the major form exposed in the plasma in rats after oral administration of MMF, but the major metabolites in the rat’s tissue disposition were MPAG.

HTA38 Accuracy and Economic Evaluation of the Interferon Gamma Release Test (IGRA) for Detection of Latent Infection By Mycobacterium Tuberculosis in Patients with Immune-Mediated Diseases or Receptors of Solid Organ Transplants

Latent tuberculosis infection (LTBI) has a high global prevalence and can progress to its active form in immunocompromised patients. There is also considerable uncertainty about diagnostic tests accuracy because there is no gold standard. The purpose was to evaluate the accuracy of the interferon gamma release test (IGRA) to detect LTBI and predict the active tuberculosis in solid organ transplant candidates (1st group) and patients with immune-mediated inflammatory diseases (2nd group).