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1.
Transplantation ; 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38548699

ABSTRACT

BACKGROUND: In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD). METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras. RESULTS: One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 (P = 0.006), it became comparable in Era 2 (P = 0.54). CONCLUSIONS: The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location.

2.
RSC Adv ; 13(21): 14484-14493, 2023 May 09.
Article in English | MEDLINE | ID: mdl-37188250

ABSTRACT

Colloidal covalent organic framework (COF) synthesis enables morphological control of crystallite size and shape. Despite numerous examples of 2D COF colloids with various linkage chemistries, 3D imine-linked COF colloids are more challenging synthetic targets. Here we report a rapid (15 min-5 day) synthesis of hydrated COF-300 colloids ranging in length (251 nm-4.6 µm) with high crystallinity and moderate surface areas (150 m2 g-1). These materials are characterized by pair distribution function analysis, which is consistent with the known average structure for this material alongside different degrees of atomic disorder at different length scales. Additionally, we investigate a series of para-substituted benzoic acid catalysts, finding that 4-cyano and 4-fluoro substituted benzoic acids produce the largest COF-300 crystallites with lengths of 1-2 µm. In situ dynamic light scattering experiments are used to assess time to nucleation in conjunction with 1H NMR model compound studies to probe the impact of catalyst acidity on the imine condensation equilibrium. We observe cationically stabilized colloids with a zeta potential of up to +14.35 mV in benzonitrile as a result of the carboxylic acid catalyst protonating surface amine groups. We leverage these surface chemistry insights to synthesize small COF-300 colloids using sterically hindered diortho-substituted carboxylic acid catalysts. This fundamental study of COF-300 colloid synthesis and surface chemistry will provide new insights into the role of acid catalysts both as imine condensation catalysts and as colloid stabilizing agents.

3.
mBio ; 13(6): e0263222, 2022 12 20.
Article in English | MEDLINE | ID: mdl-36409086

ABSTRACT

Staphylococcus epidermidis is a ubiquitous human commensal skin bacterium that is also one of the most prevalent nosocomial pathogens. The genetic factors underlying this remarkable lifestyle plasticity are incompletely understood, mainly due to the difficulties of genetic manipulation, precluding high-throughput functional profiling of this species. To probe the versatility of S. epidermidis to survive across a diversity of environmental conditions, we developed a large-scale CRISPR interference (CRISPRi) screen complemented by transcriptional profiling (RNA sequencing) across 24 diverse conditions and piloted a droplet-based CRISPRi approach to enhance throughput and sensitivity. We identified putative essential genes, importantly revealing amino acid metabolism as crucial to survival across diverse environments, and demonstrated the importance of trace metal uptake for survival under multiple stress conditions. We identified pathways significantly enriched and repressed across our range of stress and nutrient-limited conditions, demonstrating the considerable plasticity of S. epidermidis in responding to environmental stressors. Additionally, we postulate a mechanism by which nitrogen metabolism is linked to lifestyle versatility in response to hyperosmotic challenges, such as those encountered on human skin. Finally, we examined the survival of S. epidermidis under acid stress and hypothesize a role for cell wall modification as a vital component of the survival response under acidic conditions. Taken together, this study integrates large-scale CRISPRi and transcriptomics data across multiple environments to provide insights into a keystone member of the human skin microbiome. Our results additionally provide a valuable benchmarking analysis for CRISPRi screens and are a rich resource for other staphylococcal researchers. IMPORTANCE Staphylococcus epidermidis is a bacteria that broadly inhabits healthy human skin, yet it is also a common cause of skin infections and bloodstream infections associated with implanted medical devices. Because human skin has many different types of S. epidermidis, each containing different genes, our goal is to determine how these different genes allow S. epidermidis to switch from healthy growth in the skin to being an infectious pathogen. Understanding this switch is critical to developing new strategies to prevent and treat S. epidermidis infections.


Subject(s)
Staphylococcal Infections , Humans , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/genetics , Clustered Regularly Interspaced Short Palindromic Repeats , Transcriptome , Skin/microbiology
4.
Cureus ; 14(4): e24482, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35651413

ABSTRACT

OBJECTIVE: To investigate the incidence and characteristics of deep vein thrombosis (DVT) in kidney transplantation recipients and analyze whether the anatomical side of DVT was associated with the side of the transplanted organ. METHODS: A single-center retrospective medical record review of patients who received a kidney transplant between January 2004 and July 2019 and who subsequently developed DVT. Only patients who received unilateral kidney transplants were included in the study. Patients who underwent concomitant pancreatic transplants, bilateral kidney transplants, or repeat procedures were excluded. RESULTS: Of the 2449 kidney transplants performed during the study period, 1482 were included in the analysis (948 men [64%]; mean age 61 years). Of 606 duplex ultrasound tests, 115 results confirmed the presence of DVT. The incidence of symptomatic DVT was 4.7%. The most common time of DVT diagnosis was within four weeks after transplantation. Type 2 diabetes, heart failure, acute myocardial infarction, sepsis, chronic obstructive pulmonary disease/abnormal pulmonary function, and being confined to bed were associated with DVT after kidney transplant (all P < 0.05). Patients with ultrasound-confirmed DVT had higher mean Caprini scores than patients with negative duplex ultrasounds (P < 0.5). Approximately 53% of transplant patients with ultrasound-confirmed DVT had a 1:1 correlation of transplant side to the side of DVT. Cohen kappa statistic 0.03 indicated no correlation between the side of DVT and the side of transplant. CONCLUSIONS: The incidence of DVT after kidney transplant was lower than the incidence reported in the literature. Being confined to a bed may be a risk factor for DVT after transplant surgery. Kidney transplant recipients who had a positive duplex ultrasound had higher Caprini risk assessment scores than transplant recipients who had negative duplex ultrasounds. There was no correlation between the side of the DVT and the side of the transplant.

5.
Pediatr Transplant ; 26(4): e14241, 2022 06.
Article in English | MEDLINE | ID: mdl-35122460

ABSTRACT

BACKGROUND: BKV and BKVN are common in pediatric kidney transplant, but there is limited data on treatment approaches. Our objective was to study the prevalence of BKV and BKVN utilizing only plasma qPCR and report treatment outcomes with stepwise IR and IVIG. METHODS: A retrospective study of all pediatric kidney transplants from 2013 to 2020. Excluded patients >21 years at transplant and immediate graft failure. Surveillance was conducted using only plasma BK qPCR at 1, 3, 6, 9, 12, 18, and 24 months and annually. BKV defined as ≥250 copies/ml and resolution as <250 copies/ml. Presumed BKVN as >10 000 copies/ml despite IR; and BKVN if confirmed on histology. RESULTS: Fifty-six patients were included in the study; 20 (35.7%) had BKV. BKV was associated with longer duration of stent, 40 vs. 33.5 days (p = .004). Two patients (3.5%) had confirmed, and 2(3.5%) had presumed BKVN. The first-line treatment was IR in 100% of patients. BKVN confirmed and presumed received IVIG every month for six doses. Viral resolution was achieved in 70%, and no difference was noted in estimated glomerular filtration rate between BKV and non-BKV group (p = .438). There were no rejection episodes, and graft survival was 100% over median follow-up of 3 years. CONCLUSIONS: Plasma qPCR alone is adequate for screening and monitoring treatment of BKV and BKVN. A stepwise IR and IVIG resulted in BKV resolution in the majority of patients. Larger studies are required to study the role of IVIG in the treatment of BKVN.


Subject(s)
BK Virus , Immunologic Deficiency Syndromes , Kidney Diseases , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Child , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Deficiency Syndromes/complications , Immunosuppression Therapy , Kidney Diseases/complications , Male , Polyomavirus Infections/epidemiology , Retrospective Studies , Tumor Virus Infections/epidemiology
6.
Prog Transplant ; 32(1): 4-10, 2022 03.
Article in English | MEDLINE | ID: mdl-34860614

ABSTRACT

Introduction: An outstanding question in kidney transplantation is how to prepare candidates and their social supports for optimal posttransplant outcomes. Project Aims: This program evaluation assessed whether a pretransplant quality improvement clinic improved clinical outcomes in the year posttransplant compared to recipients receiving standard of care. Design: The Countdown to Transplant Clinic was implemented with kidney transplant candidates expected to receive a transplant within the next few months. The clinic included an enhanced education session on posttransplant lifestyle management, confirmation of support (≥2 adults), and evaluations by transplant social work, psychology, and nephrology. Results: Seventy-five patients participated in the clinic and underwent a transplant. A retrospective chart review of posttransplant laboratory values, rehospitalizations (within 3-months posttransplant), biopsy-confirmed graft failure, and mortality (within 1-year posttransplant) were collected from both groups. Univariate and multivariate propensity score-weighted linear or logistic regression models were used to evaluate the association between clinic participation and outcomes. In models adjusting for relevant covariates, participation in The Countdown to Transplant Clinic (vs standard care) was associated with a lower coefficient of variation of serum tacrolimus (all values collected 3-12 months posttransplant), 30-day posttransplant white blood cell counts (but not 90-day), 90-day posttransplant potassium, and 30 and 31 to 90 days rehospitalizations. Clinic participation did not predict serum glucose levels at 30- or 90-days posttransplant. Due to low rates of rejection and mortality, meaningful comparisons were not possible. Conclusion: Participation in a pretransplant, multicomponent clinic may improve certain outcomes of interest posttransplantation. Pilot testing for feasibility for randomized controlled trials is a necessary next step.


Subject(s)
Kidney Transplantation , Adult , Educational Status , Graft Rejection/prevention & control , Humans , Retrospective Studies , Risk Factors , Social Support , Tacrolimus , Transplant Recipients/psychology
7.
Clin Transplant ; 35(12): e14456, 2021 12.
Article in English | MEDLINE | ID: mdl-34717009

ABSTRACT

Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic = .59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and .58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1-year biopsy and eGFR > 40) remains difficult.


Subject(s)
Kidney Transplantation , Allografts , Biopsy , Fibrosis , Gene Expression , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Rejection/genetics , Humans , Kidney/pathology , Kidney/physiology , Kidney Transplantation/adverse effects , Prospective Studies , Retrospective Studies
8.
Nutrients ; 13(9)2021 Sep 18.
Article in English | MEDLINE | ID: mdl-34579124

ABSTRACT

This efficacy trial evaluated the effects of two polyphenolic stilbenes, resveratrol and pterostilbene, mostly found in grapes, on the brush border membrane functionality, morphology and gut microbiome. This study applied the validated Gallus gallus intra-amniotic approach to investigate the effects of stilbene administration versus the controls. Three treatment groups (5% resveratrol; 5% pterostilbene; and synergistic: 4.75% resveratrol and 0.25% pterostilbene) and three controls (18 MΩ H2O; no injection; 5% inulin) were employed. We observed beneficial morphological changes, specifically an increase in the villus length, diameter, depth of crypts and goblet cell diameter in the pterostilbene and synergistic groups, with concomitant increases in the serum iron and zinc concentrations. Further, the alterations in gene expression of the mineral metabolism proteins and pro-inflammatory cytokines indicate a potential improvement in gut health and mineral bioavailability. The cecal microbiota was analyzed using 16S rRNA sequencing. A lower α-diversity was observed in the synergistic group compared with the other treatment groups. However, beneficial compositional and functional alterations in the gut microbiome were detected. Several key microbial metabolic pathways were differentially enriched in the pterostilbene treatment group. These observations demonstrate a significant bacterial-host interaction that contributed to enhancements in intestinal functionality, morphology and physiological status. Our data demonstrate a novel understanding of the nutritional benefits of dietary stilbenes and their effects on intestinal functionality, morphology and gut microbiota in vivo.


Subject(s)
Gastrointestinal Microbiome/drug effects , Intestines/embryology , Resveratrol/administration & dosage , Stilbenes/administration & dosage , Vitis/chemistry , Amnion/drug effects , Animals , Chick Embryo/drug effects , Chickens , Cytokines/genetics , Drug Synergism , Fruit/chemistry , Gene Expression/drug effects , Intestines/microbiology , Intestines/physiology , Microvilli/physiology , Minerals/metabolism
9.
Urology ; 156: 141-146, 2021 10.
Article in English | MEDLINE | ID: mdl-34058240

ABSTRACT

OBJECTIVE: To describe the use of robotic-assisted transplant ureteral repair (RATUR) for treating transplant ureteral stricture (TUS) in 3 patients who had undergone robot assisted kidney transplant (RAKT). METHOD: We reviewed the medical records of 3 patients who experienced TUS after RAKT and who underwent RATUR between 2017 and 2020. The patients' RAKT, post-transplant clinical course, endourological interventions, reoperation, and recovery were assessed. RESULTS: All patients diagnosed with TUS presented with deterioration of kidney function after RAKT. Method of diagnosis included ultrasound, antegrade ureterogram, and CT scan. All 3 patients had a short (<1 cm) area of TUS and underwent RATUR. For 2 patients, distal strictures were bypassed with modified Lich-Gregoir ureteroneocystostomy reimplantation. One patient was treated with pyelo-ureterostomy to the contralateral native ureter. No intraoperative complications, conversions to open surgery, or significant operative blood loss requiring blood transfusion for any patient were observed. Also, no patients had urine leaks in the immediate or late postoperative period. After RATUR, 2 patients developed Clavien grade II complications with rectus hematoma or urinary tract infection. CONCLUSION: RATUR is a technically feasible operation for kidney transplant patients with TUS after RAKT. This procedure may provide the same benefits of open operation without promoting certain comorbidities that may occur from open surgical procedures.


Subject(s)
Kidney Transplantation/adverse effects , Postoperative Complications , Reoperation/methods , Robotic Surgical Procedures/methods , Ureteral Obstruction , Aged , Constriction, Pathologic/diagnosis , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Female , Humans , Kidney Function Tests/methods , Kidney Transplantation/methods , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/surgery , Replantation/methods , Treatment Outcome , Ureteral Obstruction/diagnosis , Ureteral Obstruction/etiology , Ureteral Obstruction/surgery , Ureterostomy/methods
10.
Expert Opin Drug Saf ; 19(10): 1339-1348, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32633157

ABSTRACT

OBJECTIVES: In TRANSFORM, de novo kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3-8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15. METHODS: Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19. RESULTS: The safety population consisted of 2,026 patients (EVR+rCNI: 1,014, MPA+sCNI: 1,012). The proportion of patients with at least 1 WHAE was comparable between EVR+rCNI and MPA+sCNI treatment groups [20.6% vs. 17.3%; risk ratio (RR): 1.19; 95% confidence interval (CI): 0.99, 1.43] at month 24. The numerical difference between EVR+rCNI and MPA+sCNI was mainly caused by an increased proportion of EVR patients with lymphocele and wound dehiscence [7.5% vs. 5.1% (RR: 1.46; 95% CI: 1.04, 2.05) and 3.9% vs. 1.8% (RR: 2.22; 95%CI: 1.28, 3.84), respectively] 20. CONCLUSION: The immediate introduction of EVR+rCNI after kidney transplantation was associated with an overall comparable incidence of WHAEs versus current standard-of-care over the 24-month study period. There was an increased relative risk of experiencing lymphocele and wound dehiscence but the absolute risks were rather low in both groups 21. CT.GOV IDENTIFIER: NCT01950819.


Subject(s)
Calcineurin Inhibitors/adverse effects , Everolimus/adverse effects , Immunosuppressive Agents/adverse effects , Wound Healing/drug effects , Adult , Calcineurin Inhibitors/administration & dosage , Everolimus/administration & dosage , Female , Humans , Immunosuppressive Agents/administration & dosage , Incidence , Kidney Transplantation , Lymphocele/epidemiology , Lymphocele/etiology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Risk , Surgical Wound Dehiscence/epidemiology , Surgical Wound Dehiscence/etiology
11.
Transplant Proc ; 51(10): 3227-3233, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31732207

ABSTRACT

BACKGROUND: Patients with end-stage renal disease are at increased risk for psychiatric and cognitive pathologies. Despite this, there is little standardization of the psychosocial and/or psychiatric evaluation of renal transplant candidates. The purpose of this study is to report the frequency of psychiatric and cognitive pathologies and corresponding psychiatric recommendations in a sample of patients actively listed for kidney transplant. METHODS: We performed a retrospective chart review of 104 patients listed for kidney transplant who underwent semistructured psychiatric assessments as part of a novel clinical protocol. Transplant psychiatry routinely administers brief screeners of cognitive functioning and health literacy, also collected from patients' charts. RESULTS: There were a number of primary psychiatric disorders, including active substance abuse. Even using a conservative cutoff, 52.4% of patients' charts indicated evidence of cognitive impairment, and 28.9% indicated limited health literacy. In addition, there were numerous additional recommendations made within every category (educational, psychotherapeutic/psychiatric, cognitive, cessation of substance use, substance abuse treatment, and mobilizing support for transplant). With the exclusion of the recommendation for more education regarding the transplant process, most patients had at least 1 to 3 recommendations (n = 72, 69.2%). CONCLUSIONS: We have identified a number of concerning psychosocial and psychiatric factors in patients who were evaluated and listed for kidney transplantation that can adversely impact transplant outcomes. The findings provide support for more in-depth and ongoing psychiatric assessments as standard clinical protocol for kidney transplant candidates.


Subject(s)
Kidney Failure, Chronic/psychology , Mental Disorders/complications , Psychological Tests , Adult , Female , Health Literacy , Humans , Kidney Failure, Chronic/complications , Kidney Transplantation/psychology , Male , Mental Disorders/diagnosis , Middle Aged , Retrospective Studies , Substance-Related Disorders/complications
12.
Transplantation ; 103(9): 1953-1963, 2019 09.
Article in English | MEDLINE | ID: mdl-30801548

ABSTRACT

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.


Subject(s)
Calcineurin Inhibitors/administration & dosage , Cyclosporine/administration & dosage , Everolimus/administration & dosage , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Tacrolimus/administration & dosage , Adult , Calcineurin Inhibitors/adverse effects , Cyclosporine/adverse effects , Drug Therapy, Combination , Everolimus/adverse effects , Graft Rejection/immunology , Graft Rejection/mortality , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Middle Aged , Mycophenolic Acid/administration & dosage , Risk Factors , Tacrolimus/adverse effects , Time Factors , Treatment Outcome
13.
New Phytol ; 221(4): 2096-2111, 2019 03.
Article in English | MEDLINE | ID: mdl-30289553

ABSTRACT

The production and regulation of defensive specialized metabolites play a central role in pathogen resistance in maize (Zea mays) and other plants. Therefore, identification of genes involved in plant specialized metabolism can contribute to improved disease resistance. We used comparative metabolomics to identify previously unknown antifungal metabolites in maize seedling roots, and investigated the genetic and physiological mechanisms underlying their natural variation using quantitative trait locus mapping and comparative transcriptomics approaches. Two maize metabolites, smilaside A (3,6-diferuloyl-3',6'-diacetylsucrose) and smiglaside C (3,6-diferuloyl-2',3',6'-triacetylsucrose), were identified that could contribute to maize resistance against Fusarium graminearum and other fungal pathogens. Elevated expression of an ethylene signaling gene, ETHYLENE INSENSITIVE 2 (ZmEIN2), co-segregated with a decreased smilaside A : smiglaside C ratio. Pharmacological and genetic manipulation of ethylene availability and sensitivity in vivo indicated that, whereas ethylene was required for the production of both metabolites, the smilaside A : smiglaside C ratio was negatively regulated by ethylene sensitivity. This ratio, rather than the absolute abundance of these two metabolites, was important for maize seedling root defense against F. graminearum. Ethylene signaling regulates the relative abundance of the two F. graminearum-resistance-related metabolites and affects resistance against F. graminearum in maize seedling roots.


Subject(s)
Disease Resistance , Ethylenes/metabolism , Fusarium/physiology , Plant Roots/microbiology , Seedlings/microbiology , Signal Transduction , Sucrose/metabolism , Zea mays/microbiology , Acetylation , Antifungal Agents/pharmacology , Inbreeding , Metabolome , Models, Biological , Plant Diseases/microbiology , Plant Proteins/metabolism , Plant Roots/growth & development , Quantitative Trait Loci/genetics , Zea mays/metabolism
14.
Transpl Infect Dis ; 21(1): e13026, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30414224

ABSTRACT

Emphysematous pyelonephritis (EPN) is a rare condition which can rapidly progress to sepsis and multiple organ failure with high mortality. We experienced a rare case of EPN in a renal allograft related to antibody-mediated rejection (AMR). The patient received a deceased donor kidney transplant due to end-stage renal disease secondary to diabetes mellitus. Cross-match test was negative but she had remote history of anti-HLA-A2 antibody corresponding with the donor HLA. Surgery concluded without any major events. Anti-thymoglobulin was given perioperatively for induction. She was compliant with her immunosuppressive medications making urine of 2 L/d with serum creatinine of 1.9 mg/dL at discharge on post-operative day (POD) 6. She did well until POD 14 when she presented to the clinic with features of sepsis, pain over the transplanted kidney area and decline in urine volume with elevated serum creatinine. CT revealed extensive gas throughout the transplanted kidney. Renal scan revealed non-functional transplant kidney with no arterial flow. Based on these findings, a decision to perform transplant nephrectomy was made. At laparotomy, the kidney was completely necrotic. Pathology showed non-viable kidney parenchyma with the tubules lacking neutrophilic casts suggestive of ischemic necrosis. Donor-specific antibody (DSA) returned positive with high intensity anti-HLA-A2 antibody. This is the first case of early EPN in allograft considered to have occurred as a result of thrombotic ischemia secondary to AMR. This case suggests consideration of perioperative anti-B-cell and/or anti-plasma cell therapies for historical DSA and strict post-operative follow-up in immunologically high-risk recipients to detect early signs of rejection and avoid deleterious outcomes.


Subject(s)
Emphysema/immunology , Graft Rejection/immunology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Pyelonephritis/immunology , Allografts/blood supply , Allografts/diagnostic imaging , Allografts/immunology , Allografts/pathology , Biopsy , Emphysema/diagnosis , Emphysema/pathology , Emphysema/therapy , Female , Graft Rejection/diagnosis , Graft Rejection/pathology , Graft Rejection/therapy , Graft Survival/immunology , Humans , Ischemia/diagnosis , Ischemia/immunology , Ischemia/pathology , Ischemia/therapy , Kidney/blood supply , Kidney/diagnostic imaging , Kidney/immunology , Kidney/pathology , Kidney Failure, Chronic/surgery , Middle Aged , Pyelonephritis/diagnosis , Pyelonephritis/pathology , Pyelonephritis/therapy , Radioisotope Renography , Renal Dialysis , Thromboembolism/diagnosis , Thromboembolism/immunology , Thromboembolism/pathology , Thromboembolism/therapy
15.
Ann Transplant ; 22: 563-569, 2017 Sep 19.
Article in English | MEDLINE | ID: mdl-28924138

ABSTRACT

BACKGROUND Ketorolac is a nonsteroidal anti-inflammatory drug indicated for pain control after surgeries in many fields. The aim of this study was to evaluate the impact of ketorolac use after live-donor nephrectomy (LDN). MATERIAL AND METHODS We reviewed data on 251 patients who underwent laparoscopic LDN from April 2008 to March 2016. Ketorolac was given to 167 patients intraoperatively or postoperatively within 24 h after LDN. Glomerular filtration rate (GFR) percentage was defined as postoperative GFR/preoperative GFR. GFR and GFR percentage at 2 weeks, 6 months, and 1 year after LDN were compared between patients with and without ketorolac administration. Multivariate analysis was performed to identify risk factors for low GFR percentage 1 year after LDN. RESULTS GFR at 1 year was significantly lower in patients who received ketorolac than in those who did not (62 ml/min/1.73 m² vs. 73 ml/min/1.73 m², P<0.01). The differences in GFR and GFR percentage between 2 weeks and 1 year after LDN was significantly lower in the ketorolac group (GFR; 3.0 ml/min/1.73 m² vs. 14.0 ml/min/1.73 m², P<0.01; GFR percentage; 2.0% vs. 12.0%, P<0.01). Urinary albumin/creatinine ratio 1 year after LDN was significantly higher in the ketorolac group compared to the non-ketorolac group (8.6 mg/g vs. 12.6 mg/g, P=0.02). Multivariate analysis revealed that ketorolac use was an independent risk factor for low GFR percentage 1 year after LDN (odds ratio 1.38). CONCLUSIONS Ketorolac appears to be a risk factor for renal dysfunction in the long term after LDN. Prospective clinical trials are needed to reassess its safety.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Glomerular Filtration Rate/drug effects , Ketorolac/adverse effects , Kidney/drug effects , Living Donors , Nephrectomy/methods , Renal Insufficiency/chemically induced , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Female , Humans , Ketorolac/administration & dosage , Ketorolac/therapeutic use , Kidney/physiopathology , Kidney Function Tests , Kidney Transplantation/methods , Laparoscopy/methods , Male , Middle Aged , Pain, Postoperative/drug therapy , Renal Insufficiency/physiopathology , Risk Factors
16.
World J Hepatol ; 9(22): 973-978, 2017 Aug 08.
Article in English | MEDLINE | ID: mdl-28839518

ABSTRACT

Identification of extrahepatic metastases (EHM) of hepatocellular carcinoma (HCC) has been paradoxically increasing due to an increase in the survival of HCC patients. However, metastasis of HCC to the skeletal muscle tissue is extremely rare. We describe a unique case of HCC metastasizing to the paravertebral muscle. A 55-year-old man with a history of hepatitis B cirrhosis underwent partial liver resection with complete removal of HCC. Three months later, a computed tomography (CT) scan showed intrahepatic recurrence. The tumors were treated with yttrium-90 microspheres, trans-catheter arterial chemoembolization, and sorafenib. Six months later, a CT scan showed an enhancing lesion of the left paravertebral muscle that on biopsy were consistent with metastatic HCC. The tumor was treated with stereotactic hypo-fractionated image-guided radiation therapy (SHFRT). A follow-up scan 3 mo post-radiotherapy revealed a stable appearance of the paravertebral muscle metastasis. Because of the progression in the intrahepatic tumors, the patient was treated with capecitabine, which was changed to dasatinib 6 mo later. The patient passed away three years after the primary surgical resection. Management of EHM poses an extreme challenge. This is the first case of HCC with EHM to the paravertebral muscle in which stability of disease was achieved using SHFRT. This case highlights the importance of early detection of hepatitis B viral infection and initiation of anti-viral therapy to decrease recurrence of HCC and prevent EHM.

17.
Am J Case Rep ; 18: 399-404, 2017 Apr 14.
Article in English | MEDLINE | ID: mdl-28408734

ABSTRACT

BACKGROUND Mycophenolate mofetil (MMF) induced lung disease has been described in only a few isolated reports. We report a case of fatal respiratory failure associated with MMF after kidney transplantation. CASE REPORT A 50-year-old Hispanic male with a history of end-stage renal disease secondary to hypertension underwent deceased donor kidney transplantation. His preoperative evaluations were normal except for a chest x-ray which showed bilateral interstitial opacities. Tacrolimus and MMF were started on the day of surgery. His postoperative course was uneventful and he was discharged on postoperative day 5. One month later, he presented with shortness of breath and a cough with blood-tinged sputum. His respiratory condition deteriorated rapidly, requiring intubation. Chest computer tomography (CT) demonstrated patchy ground-glass opacities with interlobular septal thickening. Comprehensive pulmonary, cardiac, infectious, and immunological evaluations were all negative. Open lung biopsy revealed extensive pulmonary fibrosis with no evidence of infection. He temporarily improved after discontinuation of tacrolimus and MMF, however, on resuming MMF his respiratory status deteriorated again and he subsequently died from hypoxic respiratory failure. CONCLUSIONS An awareness of pulmonary lung disease due to MMF is important to prevent adverse outcomes after organ transplantation. MMF must be used with utmost care in recipients with underlying lung disease as their pulmonary condition might make them more susceptible to any harmful effects of MMF.


Subject(s)
Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , Pulmonary Fibrosis/chemically induced , Fatal Outcome , Humans , Male , Middle Aged
18.
World J Transplant ; 7(1): 88-93, 2017 Feb 24.
Article in English | MEDLINE | ID: mdl-28280700

ABSTRACT

We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression.

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