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Jason A Trubiano

Publications and source records attributed to Jason A Trubiano.

2 recordsLinked to original sources

Donor Microbiota Features Associated With Liver Transplant Recipient Infectious Complications: A Pilot Study Using Deep Intestinal Sampling During Liver Procurement.

BACKGROUND: The gut microbiota of living organ donors has been linked to transplant outcomes. However, little is known about the characteristics of the deceased donor gut microbiota or its potential impact on recipient outcomes. METHODS: We analyzed the deep intestinal microbiota from 24 deceased donors. Samples included luminal stool from the right and left colon as well as bile. Microbial composition was characterized using 16S V4 rRNA sequencing. &#x3b1;- and &#x3b2;-diversity analyses were performed to compare microbial communities between donor enteric sites and against stool samples from 28 healthy community controls, 14 critically ill intensive care comparators, and 12 matched liver transplant recipients. Machine learning models and logistic regression analysis were applied to explore whether features of the donor microbiota could predict recipient post-transplant complications. FINDINGS: The deceased donor microbiota showed an absence of the expected compositional variability between sampling sites, with no significant differences in either &#x3b1;- or &#x3b2;-diversity observed between bile, right and left colonic samples (all p > 0.05). Donor samples exhibited distinct microbial profiles compared with stool from both healthy and ICU comparators, including increased abundance of potential pathogens within the Enterobacteriaceae family (all p < 0.001). Features of the donor microbiota, particularly enrichment of Enterobacteriaceae, were associated with an increased risk of early post-transplant infection in recipients (&#x2264;&#xa0;30 days; p&#xa0;=&#xa0;0.011). INTERPRETATION: The deceased donor gut microbiota may represent a distinct microbial community with potential clinical relevance. Microbial profiling of donor enteric microbiota may help identify recipients at heightened risk of early post-transplant infectious complications.

Enterobacteriaceae

HLA-B Alleles With Shared Peptide Binding Specificities Define Global Risk of Co-trimoxazole-Induced Severe Cutaneous Adverse Drug Reactions.

BACKGROUND: Co-trimoxazole is a leading global cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Co-trimoxazole-induced SCAR are associated with HLA class I alleles including HLA-B&#x2217;13:01 and HLA-B&#x2217;38:02 in Southeast Asian (SEA) populations. However, the global generalizability of these associations is unknown but critical for population-appropriate risk stratification and diagnosis. OBJECTIVE: To determine HLA risk factors associated with co-trimoxazole-induced SJS/TEN and DRESS in populations from the United States and South Africa. METHODS: We performed high-resolution HLA typing on dermatologist-adjudicated co-trimoxazole-induced patients with SCAR in the United States (n = 63) and South Africa (n = 26) compared with population controls. Peptide binding and docking analyses were performed using MHCcluster2.0 and CB-Dock2. RESULTS: In a multiple logistic regression model, HLA-B&#x2217;44:03 (corrected P [Pc] < .001; odds ratio [OR] = 4.08), HLA-B&#x2217;38:01 (Pc < .001; OR = 5.66), and HLA-C&#x2217;04:01 (Pc = .003; OR = 2.50) were independently associated with co-trimoxazole-induced SJS/TEN in the United States. HLA-B&#x2217;44:03 was also associated with co-trimoxazole-induced DRESS in South Africa (Pc = .019; OR = 10.69). Distinct HLA-B variants with shared peptide binding specificities (SPBS) and HLA-C&#x2217;04:01 identified 94% and 78% of co-trimoxazole-induced SJS/TEN and DRESS in the United States, respectively. The SEA risk allele HLA-B&#x2217;13:01, with SPBS to HLA-B&#x2217;44:03, was identified in just one of 63 US patients with SCAR. CONCLUSIONS: HLA alleles with SPBS to SEA-related risk alleles, including HLA-B&#x2217;44:03 (SPBS with HLA-B&#x2217;13:01) and HLA-B&#x2217;38:01 (SPBS with HLA-B&#x2217;38:02) but also HLA-C&#x2217;04:01, predisposed to co-trimoxazole-induced SCAR in the United States and South Africa. These findings provide biological plausibility and strategies for global risk prediction and diagnosis of co-trimoxazole-induced SCAR.

Humans