Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases.

BACKGROUND & AIMS: Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials studying the efficacy of vaccines against SARS-CoV-2. Although the clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown, many societies have recommended vaccination of this highly vulnerable patient population. METHODS: In this prospective study, we determined antibody responses to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver disease (CLD) with and without cirrhosis. RESULTS: Of the 233 patients enrolled so far, 62 were LT recipients, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Antibody titers were defined as undetectable (<0.40 U/ml), suboptimal (0.40-250 U/ml) and adequate (>250 U/ml). Of the 62 patients who had LT, antibody levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47-212 U/ml) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable antibody levels and 15 had suboptimal (median titer 41.3, range 0.49-221 U/L) antibody responses. Of the 92 patients without cirrhosis, 4 had undetectable antibody levels and 19 had suboptimal (median titer 95.5, range 4.9-234 U/L) antibody responses. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of the Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. CONCLUSIONS: Poor antibody responses after SARS-CoV-2 vaccination were seen in 61% of LT recipients and 24% of those with CLD. LAY SUMMARY: The clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown. We performed a prospective study to evaluate immune responses to COVID-19 vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 patients with cirrhosis and 92 with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody responses (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody responses when adjusted for other factors.

Past history of skin infection and risk of surgical site infection after elective surgery.

OBJECTIVE: To identify baseline patient characteristics associated with increased susceptibility to surgical site infection (SSI) after elective surgery. BACKGROUND: The Center for Medicare and Medicaid Services considers SSI to be preventable through adherence to current infection control practices; however, the etiology of wound infection is incompletely understood. METHODS: Prospective cohort study involving patients undergoing cardiac, vascular, craniotomy, and spinal surgery at 2 academic medical centers in Baltimore, MD. A comprehensive medical history was obtained at baseline, and participants were followed for 6 months using active inpatient and outpatient surveillance for deep SSI and infectious death. Infection control best practices were monitored perioperatively. The relative risk of SSI/infectious death was determined comparing those with versus those without a past medical history of skin infection using Cox proportional hazards models. RESULTS: Of 613 patients (mean [SD] = 62.3 [11.5] years; 42.1% women), 22.0% reported a history of skin infection. The cumulative incidence of deep SSI/infectious death was 6.7% versus 3.1% for those with and without a history of skin infection, respectively (unadjusted hazard ratio (HR) = 2.25; 95% confidence interval (95% CI), 0.98-5.14; P = 0.055). Risk estimates increased after adjustments for demographic and socioeconomic variables (HR = 2.82; 95% CI, 1.18-6.74; P = 0.019) and after propensity score adjustment for all potential confounders (HR = 3.41; 95% CI, 1.36-8.59; P = 0.009). Adjustments for intraoperative infection risk factors and adherence to infection control best practice metrics had no impact on risk estimates. CONCLUSIONS: A history of skin infection identified a state of enhanced susceptibility to SSI at baseline that is independent of traditional SSI risk factors and adherence to current infection control practices.

Selective induction of c-Fos immunoreactivity in the prelimbic cortex during reinstatement of heroin seeking induced by acute food deprivation in rats.

We previously reported that acute 1-day food deprivation reinstates heroin seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured, by immunohistochemistry, the expression of c-Fos following a test for food deprivation-induced reinstatement. Groups of rats (n=9-10 per group) were trained to lever-press for heroin (0.05-0.1mg/kg/infusion) or saline for 10 days (9 h/day); each infusion was paired with a cue light. Rats were then given 10 days of extinction during which the heroin and saline syringes were removed. Next, a test for reinstatement was conducted after exposure to 0 (baseline) or 1-day food deprivation. During training, lever pressing for heroin increased over days, while responding for saline infusions paired with the cue light decreased over time. During extinction, responding on the heroin-paired lever decreased over time, while responding on the saline-paired lever remained low. In heroin-trained rats, food deprivation induced a large increase in responding on the lever associated with drug infusions. Surprisingly, food deprivation also modestly increased responding in the saline-trained rats. Food deprivation selectively increased c-Fos immunoreactivity (IR) in the prelimbic cortex of heroin-trained, but not saline-trained, rats (n=4 per condition). Food deprivation also increased c-Fos IR in both heroin- and saline-trained rats in the basolateral amygdala and the ventrolateral bed nucleus of stria terminalis (BNST), but had no effect on c-Fos expression in the dorsolateral BNST, cingulate cortex, nucleus accumbens, and central amygdala. These results raise the possibility that the prelimbic cortex is involved in food deprivation-induced reinstatement of heroin seeking.