Immune outcomes of lung transplant recipients with different cytochrome P450 3A5 phenotypes after discontinuation of voriconazole antifungal prophylaxis.

INTRODUCTION: Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation. METHODS: This retrospective cohort study compares LTRs with poor (PR) versus intermediate/extensive (IE) CYP3A5 metabolizer phenotypes. The primary endpoint is cumulative immune outcomes within three months of voriconazole discontinuation; secondary endpoints include change in tacrolimus dose-to-concentration ratios after voriconazole discontinuation. RESULTS: Thirty-four patients underwent full analysis: 13 IE and 21 PR metabolizers. A higher proportion of IE metabolizers were African American (46.2% vs. 9.5%, p = .03). There was no significant difference in composite immune outcomes, though there was a proportionally higher frequency of new donor-specific antibody development in PR metabolizers (14.3% vs 7.7%, p = .56). Both groups required approximately 2.5 to 3-fold tacrolimus dose increases post-voriconazole discontinuation to re-attain therapeutic levels. CONCLUSION: This novel investigation sheds light on how CYP3A5 phenotype could be used to guide tacrolimus dosing, with the goal of preventing both toxicity and organ rejection.

An Evaluation of Continuous Infusion Rocuronium for Sustained Neuromuscular Blockade in Critically Ill Adults.

BACKGROUND: Recent medication shortages of the neuromuscular blocking agent (NMBA) cisatracurium have forced the prescribing of aminosteroidal agents such as rocuronium. There are limited data on the use and dosing of continuous infusion (CI) rocuronium in critically ill patients outside of the operating room. OBJECTIVE: We sought to describe the use of CI rocuronium for sustained neuromuscular blockade in intensive care unit (ICU) patients by characterizing the dosing, utilization, and safety profile in patients with multiple organ failure (MOF) and non-MOF. METHODS: This was a retrospective review of patients in mixed ICUs from 2 tertiary medical centers who received CI rocuronium between January 2018 and July 2019. RESULTS: A total of 46 unique rocuronium infusions were utilized for 40 patients during the evaluation period. Of these, 37% had MOF, and 41% had at least 1 organ fail during the rocuronium infusion. The median starting and maximum dose was 8 µg/kg/min. Overall, 64% of train of 4 (TOF) measurements were a TOF 0 (T0) or TOF 1 (T1), with a higher percentage of T0 or T1 in the MOF group compared with the non-MOF group (75% vs 50%). The median time to recovery was more than twice as long for the MOF compared with the non-MOF group (10 vs 4.6 hours). ICU-acquired weakness was diagnosed in 27% of survivors. CONCLUSION AND RELEVANCE: In ICU patients with MOF, continuous rocuronium infusions were associated with deep levels of paralysis and prolonged recovery times. If neuromuscular blockade is required for critically ill patients, alternative strategies could be considered.

Regional status assessment of stony corals in the US Virgin Islands.

States may protect coral reefs using biological water quality standards outlined by the Clean Water Act. This requires biological assessments with indicators sensitive to human disturbance and regional, probability-based survey designs. Stony coral condition was characterized on a regional scale for the first time in the nearshore waters of the US Virgin Islands (USVI). Coral composition, abundance, size, and health were assessed at 66 stations in the St. Croix region in fall 2007 and at 63 stations in the St. Thomas and St. John region in winter 2009. Indicators were chosen for their sensitivity to human disturbance. Both surveys were probability-based (random) designs with station locations preselected from areas covered by hardbottom and coral reef substrate. Taxa richness was as high as 21 species but more than half the area of both regions exhibited taxa richness of <10 species in the 25 m(2) transect area. Coral density was as high as 5 colonies m(-2) but more than half the area of both regions had <2 colonies m(-2). Both regions showed similar dominant species based on frequency of occurrence and relative abundance. Because of large colony sizes, Montastrea annularis provided more total surface area and live surface area than more abundant species. The surveys establish baseline regional conditions and provide a foundation for long-term regional monitoring envisioned by the USVI Department of Planning and Natural Resources. The probabilistic sampling design assures the data can be used in Clean Water Act reporting.

Evaluation of stony coral indicators for coral reef management.

Colonies of reef-building stony corals at 57 stations around St. Croix, US Virgin Islands were characterized by species, size and percentage of living tissue. Taxonomic, biological and physical indicators of coral condition were derived from these measurements and assessed for their response to gradients of human disturbance-a requirement for indicators used in regulatory assessments under authority of the Clean Water Act. At the most intensely disturbed location, five of eight primary indicators were highly correlated with distance from the source of disturbance: Coral taxa richness, average colony size, the coefficient of variation of colony size, total topographic coral surface area, and live coral surface area. An additional set of exploratory indicators related to rarity, reproductive and spawning mode and taxonomic identity were also screened. The primary indicators demonstrated sufficient precision to detect levels of change that would be applicable in a regional-scale regulatory program.