Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI).

BACKGROUND: Intraoperative hypotension is associated with an increased risk of end organ damage and death. The transient preoperative interruption of angiotensinconverting enzyme inhibitor (ACEI) therapy prior to cardiac and vascular surgeries decreases the occurrence of intraoperative hypotension. OBJECTIVE: We sought to compare the effect of two protocols for preoperative ACEI management on the risk of intraoperative hypotension among patients undergoing noncardiac, nonvascular surgeries. DESIGN: Prospective, randomized study. SETTING: Midwestern urban 489-bed academic medical center. PATIENTS: Patients taking an ACEI for at least six weeks preoperatively were considered for inclusion. INTERVENTIONS: Randomization of the final preoperative ACEI dose to omission (n = 137) or continuation (n = 138). MEASUREMENTS: The primary outcome was intraoperative hypotension, which was defined as any systolic blood pressure (SBP) < 80 mm Hg. Postoperative hypotensive (SBP < 90 mm Hg) and hypertensive (SBP >> 180 mm Hg) episodes were also recorded. Outcomes were compared using Fisher's exact test. RESULTS: Intraoperative hypotension occurred less frequently in the omission group (76 of 137 [55%]) than in the continuation group (95 of 138 [69%]) (RR: 0.81, 95% CI: 0.67 to 0.97, P = .03, NNH 7.5). Postoperative hypotensive events were also less frequent in the ACEI omission group (RR: 0.49, 95% CI: 0.28 to 0.86, P = .02) than in the continuation group. However, postoperative hypertensive events were more frequent in the omission group than in the continuation group (RR: 1.95, 95%: CI: 1.14 to 3.34, P = .01). CONCLUSIONS: The transient preoperative interruption of ACEI therapy is associated with a decreased risk of intraoperative hypotension. REGISTRATION: ClinicalTrials.gov: NCT01669434.

That Which Bends Up: A Case Report and Literature Review of Chikungunya Virus.

We present a case of chikungunya virus (CHIKV) in a 39-year-old female who developed an acute febrile illness marked by polyarthralgia and rash after returning from Saint Lucia. This epidemic-prone pathogen is increasingly likely to be encountered by primary care and hospital physicians in the coming months. The virus was first locally transmitted in the Caribbean in December 2013 and has since spread to 44 countries and 47 US states, affecting a suspected 1.2 million people. A mosquito-borne virus, CHIKV causes a severe and symmetric polyarthralgia that can relapse for months to years, creating debilitating illness and profound socioeconomic consequences. Current treatment is limited to supportive measures, which are dependent on nonsteroidal anti-inflammatory drugs. Research into immunomodulatory agents, antiviral therapies, and vaccines is ongoing. Prevention remains key in slowing the spread of disease. Patient education should focus on personal protective measures, such as insect repellant and remaining indoors, while public health departments should implement strategies to control vector breeding grounds. Given the possibility of relapsing and debilitating disease, general internists should consider CHIKV in the differential diagnosis of a returning traveler with acute onset of fever, polyarthralgia, and rash.

Site-specific labeling of proteins and peptides with trans-cyclooctene containing handles capable of tetrazine ligation.

There is a growing library of functionalized non-natural substrates for the enzyme protein farnesyltransferase (PFTase). PFTase covalently attaches these functionalized non-natural substrates to proteins ending in the sequence CAAX, where C is a cysteine that becomes alkylated, A represents an aliphatic amino acid, and X is Ser, Met, Ala, or Gln. Reported substrates include a variety of functionalities that allow modified proteins to undergo subsequent bioconjugation reactions. To date the most common strategy used in this approach has been copper catalyzed azide-alkyne cycloaddition (CuAAC). While being fast and bioorthogonal CuAAC has limited use in live cell experiments due to copper's toxicity.(1) Here, we report the synthesis of trans-cyclooctene geranyl diphosphate. This substrate can be synthesized from geraniol in six steps and be enzymatically transferred to peptides and proteins that end in a CAAX sequence. Proteins and peptides site-specially modified with trans-cyclooctene geranyl diphosphate were subsequently targeted for further modification via tetrazine ligation. As tetrazine ligation is bioorthogonal, fast, and is contingent on ring strain rather than the addition of a copper catalyst, this labeling strategy should prove useful for labeling proteins where the presence of copper may hinder solubility or biological reactivity.