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Competing Interests: The authors declare no conflicts of interest.

Nocardia is a ubiquitous environmental pathogen that causes infection primarily following inhalation into the lungs. It is generally thought to cause infection primarily in immunocompromised patients, but nonimmunocompromised individuals are also at risk of infection. We sought to compare risk factors, clinical manifestations, diagnostic approach, treatment, and mortality in immunocompromised and nonimmunocompromised adults with nocardiosis.We studied all adults with culture-proven Nocardia infection at a tertiary care hospital from 1994 to 2015 and compared immunocompromised with nonimmunocompromised patients. The immunocompromised group included patients who had a solid organ transplant, hematopoietic cell transplant (HCT), hematological or solid tumor malignancy treated with chemotherapy in the preceding 90 days, inherited immunodeficiency, autoimmune/inflammatory disorders treated with immunosuppressive agents, or high-dose corticosteroid therapy for at least 3 weeks before the diagnosis of nocardiosis.There were 112 patients, mean age 55 ± 17 years; 54 (48%) were women. Sixty-seven (60%) were immunocompromised, and 45 (40%) were nonimmunocompromised. The lung was the site of infection in 54 (81%) immunocompromised and 25 (55%) nonimmunocompromised patients. Pulmonary nocardiosis in immunocompromised patients was associated with high-dose corticosteroids, P = .002 and allogeneic HCT, P = .01, and in nonimmunocompromised patients with cigarette smoking, bronchiectasis, and other chronic lung diseases, P = .002.Cavitation occurred only in the immunocompromised group, P < .001. Disseminated infection was more common in the immunocompromised, P = .01, and was highest in solid organ transplant recipients, P = .007. Eye infection was more common in nonimmunocompromised patients, P = .009. Clinical signs and symptoms did not differ significantly between the 2 groups. The initial treatment for most patients in both groups was trimethoprim-sulfamethoxazole with or without a carbapenem. All-cause 1-year mortality was 19%; 18 (27%) immunocompromised and 3 (7%) nonimmunocompromised patients died, P = .01.Immunocompromised patients with nocardiosis had more severe disease and significantly higher mortality than nonimmunocompromised patients, but clinical presentations did not differ.

Background: Ischemic preconditioning (IPC) and pharmacological preconditioning (PPC) have both been shown to confer cardioprotective effects. However, the role of protein synthesis in preconditioning is unclear., Methods and Results: Isolated rabbit hearts were treated with cycloheximide (CHx, 10 micromol/L), a protein synthesis inhibitor at the translational level, before 2 cycles of IPC (5 minutes of global ischemia/5 minutes of reperfusion, n=6) or PPC by pinacidil (PIN, 10 micromol/L; n=6), an ATP-sensitive potassium channel opener. Six rabbit hearts received actinomycin D (Act D, 20 micromol/L; n=6), a protein synthesis inhibitor at the transcriptional level, before IPC. The left anterior descending coronary artery was then occluded for 60 minutes and reperfused for 120 minutes. Control hearts received no treatment before prolonged ischemia (n=6). Left ventricular pressure, action potential duration, and coronary flow were measured. Infarct size is expressed as a percentage of the area at risk. IPC (n=6) and PIN (n=8) hearts experienced reduced infarct size compared with control hearts (22+/-3% and 27+/-2% versus 46+/-3%, IPC and PIN versus control; P:<0.01). Translational blockade (CHx) reversed the IPC infarct size reduction effect (22+/-3% versus 48+/-4%, IPC versus CHx+IPC; P:<0.01) but not the effects of pinacidil (27+/-2% versus 29+/-3%, PIN versus CHx+PIN; P:=NS). Transcriptional blockade (Act D) did not abolish the IPC effect (23+/-5% versus 22+/-3%, Act D+IPC versus IPC; P:=NS). There were no significant differences in electromechanical function consequent to CHx and Act D treatment., Conclusions: These findings suggest an important role for protein synthesis in the mechanism for IPC-mediated protection at the translational level, which may be different from PPC.