Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Selective transfer of maternal antibodies in preterm and fullterm children.

Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.

Altered Maternal Antibody Profiles in Women With Human Immunodeficiency Virus Drive Changes in Transplacental Antibody Transfer.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children have a higher risk of severe infection, but the causes are poorly understood. Emerging data point to altered antibody transfer in women with HIV (WHIV); however, specific perturbations and the influence of antiretroviral therapy (ART) and HIV viremia remain unclear. METHODS: We evaluated antigen-specific transplacental antibody transfer across 14 antigens in paired maternal and umbilical cord plasma from 352 Ugandan women; 176 were WHIV taking ART. We measured antigen-specific immunoglobulin G (IgG) sub-class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi-nant analysis to define antigen-specific transplacental antibody transfer features. RESULTS: Global antibody transfer patterns were similar by maternal HIV serostatus, pointing to effective placental function in WHIV. However, HEU umbilical cord antibody profiles were altered, driven by perturbed WHIV seroprofiles, with higher levels of herpesvirus antibodies (P < .01 for Epstein-Barr virus, herpes simplex virus) and lower levels of classic vaccine-induced antibodies (P < .01 for tetanus, polio, Haemophilus influenzae type b), suggesting that umbilical cord antibody profile differences arise from imbalanced WHIV immunity. Abnormal WHIV antibody profiles were associated with HIV viremia, lower CD4 count, and postconception ART initiation (P = .01). CONCLUSIONS: Perturbed immune-dominance profiles in WHIV shift the balance of immunity delivered to neonates. Perturbed HIV-associated maternal antibody profiles are a key determinant of com-promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.

Measles Vaccination Elicits a Polyfunctional Antibody Response, Which Decays More Rapidly in Early Vaccinated Children.

BACKGROUND: Measles outbreaks are reported worldwide and pose a serious threat, especially to young unvaccinated infants. Early measles vaccination given to infants under 12 months of age can induce protective antibody levels, but the long-term antibody functionalities are unknown. METHODS: Measles-specific antibody functionality was tested using a systems serology approach for children who received an early measles vaccination at 6-8 or 9-12 months, followed by a regular dose at 14 months of age, and children who only received the vaccination at 14 months. Antibody functionalities comprised complement deposition, cellular cytotoxicity, and neutrophil and cellular phagocytosis. We used Pearson's r correlations between all effector functions to investigate the coordination of the response. RESULTS: Children receiving early measles vaccination at 6-8 or 9-12 months of age show polyfunctional antibody responses. Despite significant lower levels of antibodies in these early-vaccinated children, Fc effector functions were comparable with regular-timed vaccinees at 14 months. However, 3-year follow-up revealed significant decreased polyfunctionality in children who received a first vaccination at 6-8 months of age, but not in children who received the early vaccination at 9-12 months. CONCLUSIONS: Antibodies elicited in early-vaccinated children are equally polyfunctional to those elicited from children who received vaccination at 14 months. However, these antibody functionalities decay more rapidly than those induced later in life, which may lead to suboptimal, long-term protection.

Lessons from lockdown: Virtual Clinics and service reorganisation in fracture management during COVID 19 experience of an Irish Regional Trauma Unit.

BACKGROUND: Trauma places a burden on healthcare services accounting for a large proportion of Emergency Department presentations. COVID-19 spread rapidly affecting over 30 million worldwide. To manage trauma presentations the Department of Trauma & Orthopaedic Surgery reorganised service delivery. AIM: To assess the impact of service reorganisation and Virtual Clinics on patients in a Regional Unit in Ireland. METHODS: A retrospective review of trauma activity following introduction of Virtual Fracture Clinics and Theatre COVID Pathways for a 10 week period in comparison with the same 2019 period. All patients underwent both nasopharyngeal and oropharyngeal swabs PCR testing prior to operations. Theatre and outpatient activity were evaluated. Clinic data were accumulated using the Integrated Patient Management System. RESULTS: Theatre Activity: 242 patients underwent surgery in our trauma unit (mean 2.98 per list) during the COVID- 19 period. 29 cases were performed in repurposed elective hospital giving a total of 271 during the 2020 study period. 371 cases were performed in the same 2019 period (mean 4.58 per list). Outpatient Activity: We noted a 25.86% fracture clinic referral reduction during the COVID 19 period compared to 2019. There was a 150.77% increase in patients managed through Trauma Assessment Clinic. 639 patients were managed through the Virtual Fracture Clinic Pathway during COVID 19 period. CONCLUSIONS: Over one in four fracture clinic patients can be managed virtually. A new dedicated Acute Fracture Unit within our institution permitted streamlining of care and social distancing. The "Non-COVID" pathway for ambulatory trauma was essential in managing the growing presentations of these injuries.

A Sample-Sparing Multiplexed ADCP Assay.

Antibodies serve as the primary correlate of protection following most clinically approved vaccines and are thought to confer protection in part through their ability to block (neutralize) infection. Increasingly, studies have shown that beyond their blocking activities, the ability of antibodies to leverage the innate immune response may serve a vital role in protection from infection. Specifically, antibodies can drive phagocytosis, complement activation, and cellular cytotoxicity by interacting with Fc-receptors found on all innate immune cells. Measuring the capacity of antibodies to induce these functions has become critical for the identification of correlates of protection in large-scale vaccine trials. Therefore, there is a growing need to develop robust, high throughput assays able to interrogate the functional capacity of innate immune recruiting antibodies. However, in many instances, only small sample volumes are available. Nevertheless, profiling antibody functions across many pathogen-associated antigens or across global intra-pathogen variants is in high demand, making sample sparing approaches to perform this antibody evaluation critical. Here we describe the development of an approach to interrogate the functional activity of antibodies in serum against up to 5 antigen targets simultaneously. A single bead-based cellular assay was adapted to accommodate 5 different fluorescently colored beads, allowing for the concurrent investigation of antibody responses directed against multiple antigens in a single well. The multiplexed assay was as sensitive, specific, and accurate as the single antigen assay and robustly able to assess functional differences mediated by antibodies across different samples. These findings show multiplexing allows for accurate and more efficient analysis of antibody-mediated effector profiles.

The Antibodiome-Mapping the Humoral Immune Response to HIV.

PURPOSE OF REVIEW: The design of an HIV vaccine remains an elusive but top priority. Data from the non-human primate model and the first moderately protective HIV vaccine trial (RV144) point to a role for qualitative changes in humoral immune functions in protection from infection. Here, we review the current understanding of the antibody response throughout HIV infection, the known correlates of protection, and current strategies to manipulate antibodies to put an end to the epidemic. RECENT FINDINGS: Recent studies point to innate immune-recruiting antibody function in preventing infection as well as controlling viremia following infection. These data have begun to inform next-generation design of HIV vaccines and antibody therapies by uncovering new viral targets and antibody architectures to improve potency and breadth. Emerging data illustrate a role for innate immune recruiting-antibodies in conferring protection against HIV infection as well as promoting viral control and clearance, offering an unprecedented opportunity to modulate and improve antibody function to fight HIV more effectively.

Sex differences in vaccine-induced humoral immunity.

Vaccines are among the most impactful public health interventions, preventing millions of new infections and deaths annually worldwide. However, emerging data suggest that vaccines may not protect all populations equally. Specifically, studies analyzing variation in vaccine-induced immunity have pointed to the critical impact of genetics, the environment, nutrition, the microbiome, and sex in influencing vaccine responsiveness. The significant contribution of sex to modulating vaccine-induced immunity has gained attention over the last years. Specifically, females typically develop higher antibody responses and experience more adverse events following vaccination than males. This enhanced immune reactogenicity among females is thought to render females more resistant to infectious diseases, but conversely also contribute to higher incidence of autoimmunity among women. Dissection of mechanisms which underlie sex differences in vaccine-induced immunity has implicated hormonal, genetic, and microbiota differences across males and females. This review will highlight the importance of sex-dependent differences in vaccine-induced immunity and specifically will address the role of sex as a modulator of humoral immunity, key to long-term pathogen-specific protection.

Neonate-omics: Charting the Unknown Immune Response in Early Life.

The study of neonatal immunology has been hampered by lack of access to infant samples. Novel sample sparing methods and systems-wide approaches have uniquely expanded this field, demonstrating that newborn immunity varies widely but converges over the first 3 months of life. During this important time window, environmental and genetic factors impact the infant immune system and can influence lifelong immunity.

Financial impact of inaccurate Adverse Event recording post Hip Fracture surgery: Addendum to 'Adverse event recording post hip fracture surgery'.

INTRODUCTION: A study in 2011 by (Doody et al. Ir Med J 106(10):300-302, 2013) looked at comparing inpatient adverse events recorded prospectively at the point of care, with adverse events recorded by the national Hospital In-Patient Enquiry (HIPE) System. METHODS: In the study, a single-centre University Hospital in Ireland treating acute hip fractures in an orthopaedic unit recorded 39 patients over a 2-month (August-September 2011) period, with 55 adverse events recorded prospectively in contrast to the HIPE record of 13 (23.6%) adverse events. With the recent change in the Irish hospital funding model from block grant to an 'activity-based funding' on the basis of case load and case complexity, the hospital financial allocation is dependent on accurate case complexity coding. A retrospective assessment of the financial implications of the two methods of adverse incident recording was carried out. RESULTS: A total of €39,899 in 'missed funding' for 2 months was calculated when the ward-based, prospectively collected data was compared to the national HIPE data. Accurate data collection is paramount in facilitating activity-based funding, to improve patient care and ensure the appropriate allocation of resources.

The effect of time to surgery on functional ability at six weeks in a hip fracture population in Mid-West Ireland.

Patients with a hip fracture may be appropriately delayed for surgery as they require optimisation or clinical interventions to treat acute medical illnesses (Moja et al., 2012). Other patients are inappropriately delayed due to hospital factors (Brener, 2013; Lee & Elfar, 2014). Timely efficient admission and surgery is well documented as the best course of management for these patients. The aim of this prospective cohort longitudinal follow-up study was to establish if a relationship existed between duration of time spent in the Emergency Department (ED), time to surgery and functional ability in patients with hip fractures and to examine the effect prolonged waits may have on ability to return home. Functional ability for fifty one patients with a hip fracture was evaluated using the Barthel Index Score (BIS) on admission and at six weeks post-surgery. Data were analysed by using SPSS version 20. The findings reveal a change in BIS at 6 weeks for patients whose surgery is delayed. Patients who experienced long delays awaiting admission (>12 h) in the ED functioned less well (Kruskal-Wallis test p = 0.033). Correlation existed between time to surgery and returning to pre-fracture place of residence, (p = 0.000 Pearson chi-square), which also remained significant while controlling for age. Prolonged waits had an overall negative impact on patients' post-fracture functional ability. This study highlights the deleterious effects on functional ability when surgery is delayed.

Cancer screening practices and attitudes: comparison of low-income women in three ethnic groups.

OBJECTIVE: Based on the Health Belief Model, this study investigates differences among ethnically diverse, low-income women in the USA to inform better outreach strategies to encourage participation in the Centers for Disease Control & Prevention (CDC)- sponsored breast and cervical cancer early detection program. DESIGN: Program-eligible, low-income, Hispanic, Vietnamese and Cambodian American women who were over the age of 40 volunteered to be interviewed in their first language for the study. A total of 78 women completed the interviews. RESULTS: All three samples of women were more likely to perceive barriers to having a mammogram performed compared to the non-minority normative group. Hispanic and Vietnamese women were more similar in their health beliefs and behaviors than Vietnamese and Cambodian women. CONCLUSION: This study supports other research on the barriers and health belief differences found among ethnic minority women in the USA. Further, these findings suggest that it is not advisable to collapse ethnic groups into general categories such as 'Asian' when planning cancer control strategies, as differences were found by country of origin.