G4-Ligand-Conjugated Oligonucleotides Mediate Selective Binding and Stabilization of Individual G4 DNA Structures.

G-quadruplex (G4) DNA structures are prevalent secondary DNA structures implicated in fundamental cellular functions, such as replication and transcription. Furthermore, G4 structures are directly correlated to human diseases such as cancer and have been highlighted as promising therapeutic targets for their ability to regulate disease-causing genes, e.g., oncogenes. Small molecules that bind and stabilize these structures are thus valuable from a therapeutic perspective and helpful in studying the biological functions of the G4 structures. However, there are hundreds of thousands of G4 DNA motifs in the human genome, and a long-standing problem in the field is how to achieve specificity among these different G4 structures. Here, we developed a strategy to selectively target an individual G4 DNA structure. The strategy is based on a ligand that binds and stabilizes G4s without selectivity, conjugated to a guide oligonucleotide, that specifically directs the G4-Ligand-conjugated oligo (GL-O) to the single target G4 structure. By employing various biophysical and biochemical techniques, we show that the developed method enables the targeting of a unique, specific G4 structure without impacting other off-target G4 formations. Considering the vast amount of G4s in the human genome, this represents a promising strategy to study the presence and functions of individual G4s but may also hold potential as a future therapeutic modality.

European Society of Organ Transplantation (ESOT) Consensus Statement on Prehabilitation for Solid Organ Transplantation Candidates.

There is increasingly growing evidence and awareness that prehabilitation in waitlisted solid organ transplant candidates may benefit clinical transplant outcomes and improve the patient's overall health and quality of life. Lifestyle changes, consisting of physical training, dietary management, and psychosocial interventions, aim to optimize the patient's physical and mental health before undergoing surgery, so as to enhance their ability to overcome procedure-associated stress, reduce complications, and accelerate post-operative recovery. Clinical data are promising but few, and evidence-based recommendations are scarce. To address the need for clinical guidelines, The European Society of Organ Transplantation (ESOT) convened a dedicated Working Group "Prehabilitation in Solid Organ Transplant Candidates," comprising experts in physical exercise, nutrition and psychosocial interventions, to review the literature on prehabilitation in this population, and develop recommendations. These were discussed and voted upon during the Consensus Conference in Prague, 13-15 November 2022. A high degree of consensus existed amongst all stakeholders including transplant recipients and their representatives. Ten recommendations were formulated that are a balanced representation of current published evidence and real-world practice. The findings and recommendations of the Working Group on Prehabilitation for solid organ transplant candidates are presented in this article.

Asymptomatic Bacteriuria in Kidney Transplant Recipients-A Narrative Review.

Urinary tract infections (UTIs) are the most prevalent complications in kidney transplant (KTx) recipients. The most frequent finding in this group of patients is asymptomatic bacteriuria (ASB). Here, we provide an overview of the available evidence regarding ASB in KTx recipients, including its etiopathology, clinical impact and management. There is a growing body of evidence from clinical trials that screening for and treating ASB is not beneficial in most KTx recipients. However, there are insufficient data to recommend or discourage the use of a "screen-and-treat strategy" for ASB during the first 1-2 months post-transplant or in the case of an indwelling urinary catheter. Despite its frequency, ASB after KTx is still an understudied phenomenon.

Nucleoside boranephosphonates as potential therapeutic agents / Nukleozydo boranofosfoniany jako potencjalne srodki terapeutyczne.

Nucleoside boranephosphonates are nucleotide analogues in which one of the non-bridging oxygen atom of the phosphate part has been replaced by a borane group (-BH3). This modification imparts a wide spectrum of biological activity, e.g., activation of ribonuclease H, resistance to endo- and exonucleases, and their respective triphosphates are good substrates for DNA and RNA polymerases. Nucleoside boranephosphonate derivatives are used in antisense therapy, silencing gene expression using siRNA strategies, and as potential antiviral and anti-cancer prodrugs. Boranephosphonates find also applications as aptamers and as substrates in a new method of DNA sequencing. This review briefly presents potential biological applications of nucleoside boranephosphonates.

Urinary Tract Infections Caused by K. pneumoniae in Kidney Transplant Recipients - Epidemiology, Virulence and Antibiotic Resistance.

Urinary tract infections are the most common complication in kidney transplant recipients, possibly resulting in the deterioration of a long-term kidney allograft function and an increased risk of recipient's death. K. pneumoniae has emerged as one of the most prevalent etiologic agents in the context of recurrent urinary tract infections, especially with multidrug resistant strains. This paper discusses the epidemiology and risk factors associated with urinary tract infections in kidney transplant recipients, multi-drug resistance of K. pneumoniae (ESBL, KPC, NDM), treatment and pathogenesis of K. pneumoniae infections, and possible causes of recurrent UTIs. It also addresses the issue of colonization/becoming a carrier of K. pneumoniae in the gastrointestinal tract and asymptomatic bacteriuria in relation to a symptomatic UTI development and epidemiology.

The Impact of Kidney Transplantation on the Serum Fatty Acid Profile in Patients with End-Stage Kidney Disease.

Epidemiological data indicate that metabolic disturbances and increased cardiovascular risk in renal transplant patients are a significant and common problem. Therefore, it is important to search for new solutions and, at the same time, counteract the negative effects of currently used therapies. In this study, we examined the effect of kidney transplantation on the serum levels of fatty acids (FAs) in order to assess the role of these compounds in the health of transplant patients. The FA profile was analyzed by gas chromatography-mass spectrometry in the serum of 35 kidney transplant recipients, just before transplantation and 3 months later. The content of total n-3 polyunsaturated FAs (PUFAs) decreased after transplantation (3.06 ± 0.13% vs. 2.66 ± 0.14%; p < 0.05). The total amount of ultra-long-chain FAs containing 26 and more carbon atoms was significantly reduced (0.08 ± 0.009% vs. 0.05 ± 0.007%; p < 0.05). The desaturation index (18:1/18:0) increased after transplantation (3.92 ± 0.11% vs. 4.36 ± 0.18%; p < 0.05). The study showed a significant reduction in n-3 PUFAs in renal transplant recipients 3 months after transplantation, which may contribute to increased cardiovascular risk in this patient population.

Nucleoside 5'-Phosphoramidates Control the Phenylpropanoid Pathway in Vitis vinifera Suspension-Cultured Cells.

It is known that cells contain various uncommon nucleotides such as dinucleoside polyphosphates (NpnN's) and adenosine 5'-phosphoramidate (NH2-pA) belonging to nucleoside 5'-phosphoramidates (NH2-pNs). Their cellular levels are enzymatically controlled. Some of them are accumulated in cells under stress, and therefore, they could act as signal molecules. Our previous research carried out in Arabidopsis thaliana and grape (Vitis vinifera) showed that NpnN's induced the expression of genes in the phenylpropanoid pathway and favored the accumulation of their products, which protect plants against stress. Moreover, we found that NH2-pA could play a signaling role in Arabidopsis seedlings. Data presented in this paper show that exogenously applied purine (NH2-pA, NH2-pG) and pyrimidine (NH2-pU, NH2-pC) nucleoside 5'-phosphoramidates can modify the expression of genes that control the biosynthesis of both stilbenes and lignin in Vitis vinifera cv. Monastrell suspension-cultured cells. We investigated the expression of genes encoding for phenylalanine ammonia-lyase (PAL1), cinnamate-4-hydroxylase (C4H1), 4-coumarate:coenzyme A ligase (4CL1), chalcone synthase (CHS1), stilbene synthase (STS1), cinnamoyl-coenzyme A:NADP oxidoreductase (CCR2), and cinnamyl alcohol dehydrogenase (CAD1). Each of the tested NH2-pNs also induced the expression of the trans-resveratrol cell membrane transporter VvABCG44 gene and caused the accumulation of trans-resveratrol and trans-piceid in grape cells as well as in the culture medium. NH2-pC, however, evoked the most effective induction of phenylpropanoid pathway genes such as PAL1, C4H1, 4CL1, and STS1. Moreover, this nucleotide also induced at short times the accumulation of N-benzoylputrescine (BenPut), one of the phenylamides that are derivatives of phenylpropanoid and polyamines. The investigated nucleotides did not change either the lignin content or the cell dry weight, nor did they affect the cell viability throughout the experiment. The results suggest that nucleoside 5'-phosphoramidates could be considered as new signaling molecules.

Achromobacter denitrificans pneumonia in a kidney transplant recipient - dose-dependent decrease of phagocytic activity as a potential mechanism for everolimus pulmonary toxicity.

Mammalian target of rapamycin (mTOR) inhibitors inclusive regimens are associated with increased risk of pulmonary toxicity, but the underlying mechanism has not been elucidated so far. We present the case of a 68-year-old man, after deceased-donor kidney transplantation (KTx), maintained on de novo everolimus (EVR) based immunosuppression, who developed Achromobacter denitrificans pneumonia 3 months after KTx. There was clinical improvement with antibiotic treatment, but without a radiological resolution. An additional reduction of the EVR dose resulted only in partial resolution of radiological abnormalities. We performed a functional analysis of peripheral blood neutrophils and monocytes. The ability of phagocytosis and oxidative burst generation against A. denitrificans and Escherichia coli was significantly decreased on EVR treatment as compared to the control healthy person, and significantly improved after 3 weeks of EVR absence. Additionally, these processes were significantly affected by increasing doses of EVR in vitro in the control healthy donor in a dose-dependent manner. EVR discontinuation, with no additional antibiotic treatment, resulted in complete recovery and resolution of pulmonary infiltrates. Our findings suggest that dose-dependent impairment of neutrophil/monocyte phagocytic activity and oxidative burst generation might be a potential mechanism for EVR pulmonary toxicity.

Small Extracellular Vesicles in Transplant Rejection.

Small extracellular vesicles (sEV), which are released to body fluids (e.g., serum, urine) by all types of human cells, may stimulate or inhibit the innate and adaptive immune response through multiple mechanisms. Exosomes or sEV have on their surface many key receptors of immune response, including major histocompatibility complex (MHC) components, identical to their cellular origin. They also exhibit an ability to carry antigen and target leukocytes either via interaction with cell surface receptors or intracellular delivery of inflammatory mediators, receptors, enzymes, mRNAs, and noncoding RNAs. By the transfer of donor MHC antigens to recipient antigen presenting cells sEV may also contribute to T cell allorecognition and alloresponse. Here, we review the influence of sEV on the development of rejection or tolerance in the setting of solid organ and tissue allotransplantation. We also summarize and discuss potential applications of plasma and urinary sEV as biomarkers in the context of transplantation. We focus on the attempts to use sEV as a noninvasive approach to detecting allograft rejection. Preliminary studies show that both sEV total levels and a set of specific molecules included in their cargo may be an evidence of ongoing allograft rejection.

Polymorphic variants in genes related to stress coping are associated with the awake bruxism.

BACKGROUND: Chronic stress is one of the leading predisposing factors in bruxism aetiology, but the influence of genetic factors is also suggested. We aimed to study whether sequence variants in genes involved in stress regulation pathways: NTRK2 and BDNF, may be associated with awake bruxism susceptibility, clinical presentation, and patients' perceived stress level. METHODS: The study group included 104 patients with probable awake bruxism and 191 population controls. Patients underwent dental examination concerning the symptoms of bruxism and psychological testing. Genotyping was performed using HRMA and sequencing. Statistical analyses were conducted, and P values below 0.05 were considered statistically significant. RESULTS: We observed a positive correlation of measured stress level and pathological teeth attrition in the anterior segment (r = 0.45, P < 0.001), enamel attritions (r = 0.44, P < 0.001), tongue impressions (r = 0.50, P < 0.001) and posterior teeth attrition (r = 0.27, P = 0.005). Moreover, the c.196A variant (p.66Met) of the BDNF gene and c.1397-31392G allele of the NTRK2 gene were present with elevated frequency, comparing to controls. CONCLUSIONS: This study hence the thesis that perceived stress level is a substantial contributing factor to awake bruxism occurrence and its clinical manifestations. Moreover, sequence variants in genes related to stress coping may be correlated with awake bruxism's susceptibility via elevated perceived stress level.

Changes of urine isolates of Escherichia coli and Klebsiella pneumoniae biofilm affect monocytes' response.

The Gram negative rods as Escherichia coli and Klebsiella pneumoniae belong to the most common etiology agents of urinary tract infections. The aim of our study was to assess the diversity of biofilm formed in different urinary tract diseases and their impact on monocytes' adherence and activation. The bacteria were obtained from patients with different kidney problems. Some of the patients were after renal transplantation, some of them were not. Changes in the size and granularity of monocytes, as well as their adherence to biofilm, were assessed using FACSVerse flow cytometer after 1 h co-incubation of monocytes and bacterial biofilm in 37 °C. The obtained results were validated against monocytes incubated without bacteria. The isolates from patients with chronic kidney disease formed the most adherent biofilm regardless the presence or absence of inflammatory reaction. Adherence of monocytes also increased during therapy with immunosuppressive agents, but monocytes' response was different when cyclosporine or tacrolimus were used. Additionally the presence of inflammatory reaction in patients with kidney disease modified the monocytes response when the immunosuppressive drugs were used. Considering the obtained results, we conclude that the changes of monocytes' morphology in response to biofilm formed by Gram negative rods could become a tool to detect urinary tract infection, especially in those groups of patients, where the knowledge of ongoing inflammation is important and the standard tools fail to detect it.

Genetic Background and Antibiotic Resistance Profiles of K. pneumoniae NDM-1 Strains Isolated from UTI, ABU, and the GI Tract, from One Hospital in Poland, in Relation to Strains Nationally and Worldwide.

In recent years, there has been an observed increase in infections caused by carbapenem-resistant Klebsiella pneumonia (Kp) strains. The aim of this study was the phenotypic and genotypic analysis of eight K. pneumoniae NDM (Kp NDM) isolates, recovered in Poland during the years 2016 and 2018 from seven patients with urinary tract infections (UTIs), asymptomatic bacteriuria (ABU), or colonization of the gut. PCR melting profile genotyping indicated a close relationship between the strains derived from 2018, which were not related to the strain isolated in 2016. WGS results were analyzed in relation to international Kp isolates. Clonal and phylogenetic analyses were performed based on multilocus sequence typing (MLST) and single nucleotide polymorphisms (SNPs) of the core genome. The metallo-ß-lactamase was assigned to the NDM-1 type and the sequence was identified as ST11. Eleven antimicrobial resistance genes were detected, mostly from plasmid contigs. Unprecedented profiles of plasmid replicons were described with the IncFII/pKPX-1 dominant replicon. In terms of the KL24 and O2v1 capsular antigen profiles, these isolates corresponded to Greek strains. Strains isolated from UTI, ABU, and colonization GI tract patients were not carrying environment-specific virulence genes. Based on the assessment of strain relationships at the genome level and their direction of evolution, the international character of the sublines was demonstrated, with a documented epidemic potential in Poland and Greece. In conclusion, some groups of patients, e.g., renal transplant recipients or those with complicated UTIs, who are frequently hospitalized and undergoing antibiotic therapy, should be monitored not only for the risk of UTI, but also for colonization by Kp NDM strains.

The utility of cytolytic flow cytometry crossmatch before kidney transplantation.

The donor/recipient matching in kidney transplantation is based on approved laboratory tests, which are complement-dependent cytotoxic crossmatch (CDC-XM) and flow cytometry crossmatch (FCXM). Both have some disadvantages: CDC-XM has low sensitivity, whereas FCXM does not differentiate between lytic vs. non-lytic alloantibodies. To find an improved method, we have developed a new crossmatch technique of cytolytic flow cytometry crossmatch (cFCXM), which allows for sensitive detection of clinically relevant complement-binding antibodies. The cFCXM assay detects dead cells with viability dye that ensue from the binding of allospecific lytic antibodies. In our study, 135 unsensitized kidney transplant recipients were recruited based on the CDC-XM and FCXM results and the clinical utility of cFCXM was evaluated. The 5-year follow-up for acute rejection incidents revealed that cFCXM could verify the clinical relevance of positive FCXM results as recipients with positive FCXM but negative CDC-XM had the same risk of rejection as patients with both negative CDC-XM/FCXM results. These findings suggest that cFCXM assay may provide more precise immunological risk assessment in kidney transplant recipients.

Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14-21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0-1620.0) BAU/mL and 1629.0 (1205-1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144-837) BAU/mL and 1620 (671-2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.

The New Klebsiellapneumoniae ST152 Variants with Hypermucoviscous Phenotype Isolated from Renal Transplant Recipients with Asymptomatic Bacteriuria-Genetic Characteristics by WGS.

Klebsiellapneumoniae (Kp) is one of the most important etiological factors of urinary tract infections in renal transplant (RTx) recipients. We described the antimicrobial susceptibility phenotypes and genomic features of two hypermucoviscous (HM) Kp isolates recovered from RTx recipients with asymptomatic bacteriuria (ABU). Using whole genome sequencing (WGS) data, we showed that the strains belong to the ST152 lineage with the KL149 capsular serotype, but without rmpA/magA genes, which is typical for HM+ hypervirulent Kp. These new strains carried virulence-associated genes that predispose for urinary tract infections (UTIs). Likewise, both strains carried the ecp gene encoding pilus common for extended-spectrum ß-lactamase (ESBL) Escherichiacoli. Although the two ST152 isolates were closely related and differed by only nine single nucleotide polymorphisms (SNPs) in their chromosomes, they had different plasmid compositions and chromosomal elements, with isolate KP28872 carrying an ESBL plasmid and an integrative conjugative element. These two isolates are an example of the high plasticity of the K. pneumoniae accessory genome. The identification of patients with ABU matched with the correct epidemiological profiling of isolates could facilitate interventions to prevent or rapidly treat K. pneumoniae infections.

"Old School" Islet Purification Based on the Unit Gravity Sedimentation as a Rescue Technique for Intraportal Islet Transplantation-A Case Report.

Here, we present a case that required a supplemental "old school" islet purification for a safe intraportal infusion. Following pancreas procurement from a brain-dead 26-year-old male donor (body mass index: 21.9), 24.6 ml of islet tissue was isolated after continuous density gradient centrifugation. The islet yield was 504,000 islet equivalent (IEQ), distributed among the following three fractions: 64,161 IEQ in 0.6 ml of pellet, 182,058 IEQ in 10 ml, and 258,010 IEQ in 14 ml with 95%, 20%, and 10% purity, respectively. After a 23-h culture, we applied supplemental islet purification, based on the separation of tissue subfractions during unit gravity sedimentation, a technique developed over 60 years ago ("old school"). This method enabled the reduction of the total pellet volume to 11.6 ml, while retaining 374,940 IEQ with a viability of over 90%. The final islet product was prepared in three infusion bags, containing 130,926 IEQ in 2.6 ml of pellet, 108,079 IEQ in 4 ml of pellet, and 135,935 IEQ in 5 ml of pellet with 65%, 40%, and 30% purity, respectively, and with the addition of unfractionated heparin (70 units/kg body weight). Upon the islet infusion from all three bags, portal pressure increased from 7 to 16 mmHg. Antithrombotic prophylaxis with heparin was continued for 48 h after the infusion, with target activated partial thromboplastin time 50-60 s, followed by fractionated heparin subcutaneous injections for 2 weeks. ß-Cell graft function assessed on day 75 post-transplantation was good, according to Igls criteria, with complete elimination of severe hypoglycemic episodes and 50% reduction in insulin requirements. Time spent within the target glucose range (70-180 mg/dl) improved from 42% to 98% and HbA1c declined from 8.7% to 6.7%. Supplemental "old school" islet purification allowed for the safe and successful utilization of a robust and high-quality islet preparation, which otherwise would have been discarded.

Reaction of Boranephosphonate Diesters with Pyridines or Tertiary Amines in the Presence of Iodine: Synthetic and Mechanistic Studies.

Boranephosphonate diesters react with heteroaromatic and certain tertiary amines in the presence of an oxidant (I2) to afford the boron-modified phosphodiester analogues containing a P-B-N structural motif. Our multinuclear 31P and 11B NMR spectroscopy studies lend support for a two-step mechanism involving generation of a λ3-boranephosphonate intermediate that immediately coordinates an amine in the solvent cage, leading to B-pyridinium or B-ammonium boranephosphonate betaine derivatives. We found that the type of the solvent used (e.g., dichloromethane vs acetonitrile) significantly affected the course of the reaction, resulting in either formation of boron-modified derivatives or loss of the boron group with a subsequent oxidation of the phosphorus atom. In aprotic, electron-donating, polar solvents., e.g., acetonitrile (ACN) and tetrahydrofuran (THF), a λ3-boranephosphonate intermediate can also coordinate solvent molecules forming P-B-ACN or P-B-THF complexes that may influence the type of the products formed.

BETA-2 score is an early predictor of graft decline and loss of insulin independence after pancreatic islet allotransplantation.

This study aimed to evaluate whether the BETA-2 score is a reliable early predictor of graft decline and loss of insulin independence after islet allotransplantation. Islet transplant procedures were stratified into 3 groups according to clinical outcome: long-term insulin independence without islet graft decline (group 1, N = 9), initial insulin independence with subsequent islet graft decline and loss of insulin independence (group 2, N = 13), and no insulin independence (group 3, N = 13). BETA-2 was calculated on day 75 and multiple times afterwards for up to 145 months posttransplantation. A BETA-2 score cut-off of 17.4 on day 75 posttransplantation was discerned between group 1 and groups 2 and 3 (area under the receiver operating characteristic 0.769, P = .005) with a sensitivity and negative predictive value of 100%. Additionally, BETA-2 ≥ 17.4 at any timepoint during follow-up reflected islet function required for long-term insulin independence. While BETA-2 did not decline below 17.4 for each of the 9 cases from group 1, the score decreased below 17.4 for all transplants from group 2 with subsequent loss of insulin independence. The reduction of BETA-2 below 17.4 predicted 9 (1.5-21) months in advance subsequent islet graft decline and loss of insulin independence (P = .03). This finding has important implications for posttransplant monitoring and patient care.

Early Infectious Complications After Total Pancreatectomy with Islet Autotransplantation: a Single Center Experience.

INTRODUCTION: We assessed whether positive microbiological cultures from the islet preparation had any effect on the risk of infectious complications (IC) after total pancreatectomy with islet autotransplantation (TPIAT) in our center. METHODS: We analyzed preservation fluid and final islet product surveillance cultures with reference to clinical data of patients undergoing TPIAT. All patients received routine prophylactic broad-spectrum antibiotics. RESULTS: The study involved 10 men and 18 women with a median age of 39 years. Over 30% of surveillance cultures during pancreas processing grew bacterial strains with predominantly polymicrobial contaminations (13 of 22 (59%)). At least one positive culture was identified in almost half of the patients (46%) undergoing TPIAT and a third had both surveillance cultures positive. Infectious complications affected 50% of patients. After excluding cases of PICC line-associated bacteremia/fungemia present on admission, incidence of IC was higher in cases of positive final islet product culture than in those with negative result (57% vs. 21%), which also corresponded with the duration of chronic pancreatitis (p = 0.04). Surgical site infections were the most common IC, followed by fever of unknown origin. There was no concordance between pathogens isolated from the pancreas and those identified during the infection. CONCLUSIONS: While IC was common among TPIAT patients, we found no concordance between pathogens isolated from the pancreas and those identified during infection. Contamination of the final islet product was of clinical importance and could represent a surrogate marker for higher susceptibility to infection.