Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients.

BACKGROUND: Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. METHODS: We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. RESULTS: A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. CONCLUSIONS: In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Use of triazoles for the treatment of invasive aspergillosis: A three-year cohort analysis.

In a 3-year cohort study of adult patients with proven or probable IA, fewer patients initially treated with isavuconazole experienced adverse events compared with voriconazole, but more patients required a change in therapy due to lack of clinical efficacy.

Risk of Latent Tuberculosis Reactivation After Hematopoietic cell Transplantation.

There were no cases of tuberculosis in a cohort of 2531 patients who underwent hematopoietic cell transplantation from 2010 to 2015 after 7323 person-years of follow up (95% confidence interval [CI], 0.0-0.05 cases/100 person-years), including 29 (1.15%) patients with untreated latent tuberculosis after 89 person-years of follow-up (95% CI, 0.0-4.06 cases/100 person-years).

Neuro-anatomical localization of EEG identical bursts in patients with and without post-anoxic myoclonus.

BACKGROUND: The electroencephalograph (EEG) pattern of burst suppression with identical bursts (BSIB), with or without myoclonus, occurs often after resuscitation from cardiac arrest. These patterns are associated with severe brain injury but their neuropathological basis is unknown. Using EEG source localization, we tested whether post-cardiac arrest myoclonus was associated with specific anatomical distribution of BSIB. METHODS: We performed a single center, case-control study of EEG-monitored post-cardiac arrest patients with BSIB. We determined the presence of myoclonus from clinical notes and video recordings. We generated normalized source density maps (sLORETA) for the first 0.5 s of each burst projected onto a standard anatomic model, and compared proportion of EEG power in the precentral gyrus (motor cortex) to the rest of the brain. RESULTS: We included 20 patients, 10 with and 10 without myoclonus. Patients with myoclonus had greater electrical activation localized to the precentral gyrus compared to those without (median 3.25 [IQR 2.74-3.59] vs 2.68 [IQR 2.66-2.71], P = 0.04). There was no difference between groups in region of burst origin. CONCLUSION: Among patients with BSIB after cardiac arrest, those with clinical myoclonus have more electrocortical activation in the precentral gyrus.

Awakening from post anoxic coma with burst suppression with identical bursts.

BACKGROUND: Electroencephalography (EEG) is commonly used after cardiac arrest. Burst suppression with identical bursts (BSIB) has been reported as a perfectly specific predictor of poor outcome but published case series are small. We describe two patients with BSIB who awakened from coma after cardiac arrest. METHODS: We identified two out-of-hospital cardiac arrest (OHCA) patients with coma and BSIB. We determined the etiology of arrest, presenting neurological examination, potential confounders to neurological assessment, neurodiagnostics and time to awakening. We reviewed and interpreted EEGs using 2021 American Clinical Neurophysiology Society guidelines. We quantified identicality of bursts by calculating pairwise correlation coefficients between the first 500 ms of each aligned burst. RESULTS: In case one we present a 62-year-old man with OHCA secondary to septic shock. EEG showed burst suppression pattern, with bursts consisted of high amplitude generalized spike waves in lock-step with myoclonus (inter-burst correlation = 0.86). He followed commands 3 days after arrest, when repeat EEG showed a continuous, variable and reactive background without epileptiform activity. Case two was a 49-year-old woman with OHCA secondary to polysubstance overdose. Initial EEG revealed burst suppression with high amplitude generalized polyspike-wave bursts with associated myoclonus. She followed commands on post-arrest day 4, when repeat EEG showed a continuous, variable and reactive background with frequent runs of bifrontal predominant sharply contoured rhythmic delta activity. CONCLUSION: These cases highlight the perils of prognosticating with a single modality in comatose cardiac arrest patients.