Evaluation and Recommendations on Good Clinical Laboratory Practice Guidelines for Phase I–III Clinical Trials

Marcella Sarzotti-Kelsoe and colleagues harmonize various approaches to Good Clinical Laboratory Practice for clinical trials into a single set of recommendations

Abstract 13849: Characteristics and Outcomes of COVID-19 in Patients With a Left Ventricular Assist Device

Abstract only Introduction: Patients with left ventricular assist devices (LVAD) are at increased risk for SARS-CoV-2 (COVID-19) complications. There is paucity of literature on factors influencing outcomes of LVAD patients with COVID-19 infection. Methods: A single center retrospective chart review of LVAD patients diagnosed with COVID-19 between March 2020 and March 2023, was performed to define the clinical characteristics and outcomes in this cohort. Demographics, clinical, laboratory, and imaging variables were analyzed. Results: Of 130 LVAD patients, 34 (26.2%) developed COVID-19. The cohort comprised of 27 males (79.4%) with a median age of 63.5 years and BMI of 27.6 (Table 1). Twenty-one had non-ischemic cardiomyopathy (61.8%) with either Heartmate 2 or Heartmate 3 LVADs (38.2% each). Most patients reported NYHA class III (44.1%). The common comorbidities included hypertension (94.1%), hyperlipidemia (79.4%), atrial fibrillation (67.4%), and chronic kidney disease (61.8%). Twenty-eight (82.4%) patients were hospitalized and 2 (7.1%) required mechanical ventilation (Table 2). The average initial and peak INR were 2.39 and 3.26, respectively. No complications of pump hemolysis or thrombosis, or systemic embolisms were noted. Two deaths were reported: one passed away while in the hospital from COVID-19, and another 16 months later due to sequelae of post-COVID pulmonary fibrosis. Conclusions: This is the largest single center study analyzing outcomes of COVID-19 in LVAD patients to date. Our cohort experienced a lower mortality rate from COVID-19 infection compared to prior studies. Larger studies are needed to guide management strategies and analyze long-term outcomes

Cefazolin plus ertapenem and heart transplantation as salvage therapy for refractory LVAD infection due to methicillin‐susceptible Staphylococcus aureus: A case series

The use of left ventricular assist devices (LVADs) is increasingly more common as the availability of donor organs in relation to failing hearts is outstandingly limited. Infections are the most common complications in LVAD recipients, particularly those caused by Staphylococcus spp. Refractory LVAD‐related infections are not uncommon as achieving adequate source control is often not feasible before heart transplantation. Evidence suggest that cefazolin plus ertapenem is effective in refractory methicillin‐susceptible Staphylococcus aureus (MSSA) bacteremia, but this approach has not been described in LVAD recipients. In this article, we report two cases of refractory MSSA bacteremia in LVAD recipients that were successfully treated with salvage therapy with cefazolin plus ertapenem and subsequent heart transplantation. This treatment strategy should be considered in patients with refractory LVAD‐associated infection due to MSSA that are not responding to standard treatment

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively,p= 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23–4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p= 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641