Retrospective study of testosterone deficiency and symptom burden in patients with pancreatic cancer.

Background: Pancreatic cancer patients have poor quality of life. Testosterone deficiency is associated with constitutional symptoms and sexual dysfunction which may contribute to poor quality of life. We investigated the prevalence of screening for and presence of testosterone deficiency in male pancreatic cancer patients. Methods: To determine the frequency of screening for testosterone deficiency in pancreatic cancer patients, our institution's electronic medical record system was queried for male patients diagnosed with a pancreatic mass between 2006 and 2020 and an available testosterone level. In a separate analysis, total testosterone was measured in serum samples from a cohort of 89 male pancreatic ductal adenocarcinoma (PDAC) patients. Low serum testosterone was defined as <300 ng/dL. Results: One thousand five hundred and sixty-six male patients were identified with a pancreatic mass, and 35 (2.2%) also had a testosterone level. In our analysis cohort, 44 of 89 patients (49.4%) were found to have low serum testosterone. Symptoms consistent with testosterone deficiency were documented for 70% of these patients, with fatigue being the most common. Testosterone level had no significant association with progression-free survival (PFS) (P=0.66) or overall survival (OS) (P=0.95). Conclusions: Testosterone deficiency is common but rarely assessed in male patients with pancreatic cancer. Further studies are warranted to explore the possibility of testosterone supplementation to improve quality of life in this patient population.

What Are the Barriers to Incorporating Nutrition Interventions Into Care of Older Adults With Femoral Fragility Fractures?

Femoral fragility fractures cause substantial morbidity and mortality in older adults. Mortality has generally been approximated between 10-20% in the first year after fracture and among those who do survive, another 20-60% require assistance with basic activities within 1-2 years following fracture.1 Malnutrition is common and perpetuates these poor outcomes. Nutrition supplementation has potential to prevent post-injury malnutrition, preserve functional muscle mass, and improve outcomes in older adults with femoral fragility fractures, however high-quality evidence is lacking, thus limiting translation of interventions into clinical practice. This review article is designed to highlight gaps in the evidence investigating nutrition interventions in this population and identify barriers for translation to clinical practice. Our goal is to guide future nutrition intervention research in older adults with femoral fragility fractures. Level of Evidence: V.

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors.

Vaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to measure patient antibody levels before and after transfusion with COVID-19 Convalescent Plasma (CCP) and compare the antibody levels following transfusion of CCP from vaccinated and nonvaccinated donors. Plasma samples before and after transfusion were obtained from 25 recipients of CCP and COVID-19 antibody levels measured. Factors that effect changes in antibody levels were examined. In the 21 patients who received CCP from nonvaccinated donors, modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose, calculated by the unit volume multiplied by the donor antibody level. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with reasonable accuracy(R2> 0.90). In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19. If available, CCP from vaccinated donors with very high antibody levels should be used. One unit of CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors.