Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease.

The immune mechanisms mediating COVID-19 vaccine attenuation of COVID-19 remain undescribed. We conducted comprehensive analyses detailing immune responses to SARS-CoV-2 virus in blood post-vaccination with ChAdOx1 nCoV-19 or a placebo. Samples from randomised placebo-controlled trials (NCT04324606 and NCT04400838) were taken at baseline, onset of COVID-19-like symptoms, and 7 days later, confirming COVID-19 using nucleic amplification test (NAAT test) via real-time PCR (RT-PCR). Serum cytokines were measured with multiplexed immunoassays. The transcriptome was analysed with long, short and small RNA sequencing. We found attenuation of RNA inflammatory signatures in ChAdOx1 nCoV-19 compared with placebo vaccinees and reduced levels of serum proteins associated with COVID-19 severity. KREMEN1, a putative alternative SARS-CoV-2 receptor, was downregulated in placebo compared with ChAdOx1 nCoV-19 vaccinees. Vaccination ameliorates reductions in cell counts across leukocyte populations and platelets noted at COVID-19 onset, without inducing potentially deleterious Th2-skewed immune responses. Multi-omics integration links a global reduction in miRNA expression at COVID-19 onset to increased pro-inflammatory responses at the mRNA level. This study reveals insights into the role of COVID-19 vaccines in mitigating disease severity by abrogating pro-inflammatory responses associated with severe COVID-19, affirming vaccine-mediated benefit in breakthrough infection, and highlighting the importance of clinically relevant endpoints in vaccine evaluation.

Abnormal cleavage up to Day 3 does not compromise live birth and neonatal outcomes of embryos that have achieved full blastulation: a retrospective cohort study.

STUDY QUESTION: Do embryos displaying abnormal cleavage (ABNCL) up to Day 3 have compromised live birth rates and neonatal outcomes if full blastulation has been achieved prior to transfer? SUMMARY ANSWER: ABNCL is associated with reduced full blastulation rates but does not impact live birth rates and neonatal outcomes once full blastulation has been achieved. WHAT IS KNOWN ALREADY?: It is widely accepted that ABNCL is associated with reduced implantation rates of embryos when transferred at the cleavage stage. However, evidence is scarce in the literature reporting birth outcomes from blastocysts arising from ABNCL embryos, likely because they are ranked low priority for transfer. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 1562 consecutive autologous in vitro fertilization cycles (maternal age 35.1 ± 4.7 years) performed at Fertility North, Australia between January 2017 and June 2022. Fresh transfers were performed on Day 3 or 5, with remaining embryos cultured up to Day 6 before vitrification. A total of 6019 embryos were subject to blastocyst culture, and a subset of 664 resulting frozen blastocysts was included for live birth and neonatal outcome analyses following single transfers. PARTICIPANTS/MATERIALS, SETTING, METHODS: ABNCL events were annotated from the first mitotic division up to Day 3, including direct cleavage (DC), reverse cleavage (RC) and <6 intercellular contact points at the 4-cell stage (<6ICCP). For DC and RC in combination, the ratios of affected blastomeres over the total number of all blastomeres up to Day 3 were also recorded. All pregnancies were followed up until birth with gestational age, birthweight, and sex of the baby being recorded. MAIN RESULTS AND THE ROLE OF CHANCE: Full blastulation rates for embryos showing DC (19.5%), RC (41.7%), <6ICCP (58.8%), and mixed (≥2) ABNCL types (26.4%) were lower than the rates for those without ABNCL (67.2%, P < 0.01 respectively). Subgroup analysis showed declining full blastulation rates with increasing ratios of combined DC/RC affected blastomeres over all blastomeres up to the 8-cell stage (66.2% when 0 affected, 47.0% when 0.25 affected, 27.4% when 0.5 affected, 14.5% when 0.75 affected, and 7.7% when all affected, P < 0.01). However, once full blastulation had been achieved, no difference was detected between DC, RC, <6ICCP, and no ABNCL blastocysts following single frozen transfers in subsequent live birth rates (25.9%, 33.0%, 36.0% versus 30.8%, P > 0.05, respectively), gestational age (38.7 ± 1.6, 38.5 ± 1.2, 38.3 ± 3.5 versus 38.5 ± 1.8 weeks, P > 0.05, respectively) and birthweight (3343.0 ± 649.1, 3378.2 ± 538.4, 3352.6 ± 841.3 versus 3313.9 ± 509.6 g, P > 0.05, respectively). Multiple regression (logistic or linear as appropriate) confirmed no differences in all of the above measures after accounting for potential confounders. LIMITATIONS, REASONS FOR CAUTION: Our study is limited by its retrospective nature, making it impossible to control every known or unknown confounder. Embryos in our dataset, being surplus after selection for fresh transfer, may not represent the general embryo population. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the incremental impact of ABNCL, depending on the ratio of affected blastomeres up to Day 3, on subsequent full blastulation. The reassuring live birth and neonatal outcomes of ABNCL blastocysts imply a potential self-correction mechanism among those embryos reaching the blastocyst stage, which provides valuable guidance for clinical practice and patient counseling. STUDY FUNDING/COMPETTING INTEREST(S): This research is supported by an Australian Government Research Training Program (RTP) Scholarship. All authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Current use of the National Surgical Quality Improvement Program surgical risk calculator in academic surgery: a mixed-methods study.

Background: This study aims to quantitatively assess use of the NSQIP surgical risk calculator (NSRC) in contemporary surgical practice and to identify barriers to use and potential interventions that might increase use. Materials and methods: We performed a cross-sectional study of surgeons at seven institutions. The primary outcomes were self-reported application of the calculator in general clinical practice and specific clinical scenarios as well as reported barriers to use. Results: In our sample of 99 surgeons (49.7% response rate), 73.7% reported use of the NSRC in the past month. Approximately half (51.9%) of respondents reported infrequent NSRC use (<20% of preoperative discussions), while 14.3% used it in ≥40% of preoperative assessments. Reported use was higher in nonelective cases (30.2% vs 11.1%) and in patients who were ≥65 years old (37.1% vs 13.0%), functionally dependent (41.2% vs 6.6%), or with surrogate consent (39.9% vs 20.4%). NSRC use was not associated with training status or years in practice. Respondents identified a lack of influence on the decision to pursue surgery as well as concerns regarding the calculator's accuracy as barriers to use. Surgeons suggested improving integration to workflow and better education as strategies to increase NSRC use. Conclusions: Many surgeons reported use of the NSRC, but few used it frequently. Surgeons reported more frequent use in nonelective cases and frail patients, suggesting the calculator is of greater utility for high-risk patients. Surgeons raised concerns about perceived accuracy and suggested additional education as well as integration of the calculator into the electronic health record.

Submental island flap - should we be worried about lymph node transfer? An anatomical and histological study.

The submental island flap has been increasing in popularity for both oncological and non-oncological reconstruction of the head and neck. However, the original description of this flap left it with the unfortunate designation as a lymph node flap. There has thus been significant debate on the oncological safety of the flap. In this cadaveric study the perforator system suppling the skin island is delineated and the lymph node yield of the skeletonised flap is analysed histologically. A safe and consistent approach to raising the perforator flap modification is described and the pertinent anatomy, and an oncological discussion with regards to the submental island perforator flap histological lymph node yield discussed. Ethical approval was received from Hull York Medical School for the anatomical dissection of 15 sides of cadavers. 6 x 4cm submental island flaps were raised following a vascular infusion of a 50/50 mix of acrylic paint. The flap size mimics the T1/T2 tumour defects these flaps would usually be used to reconstruct.The submental vascular anatomy, including length, diameter, venous drainage patterns, and the skin perforator system was documented. The dissected submental flaps were then histologically examined for the presence of lymph nodes by a head and neck pathologist at Hull University Hospitals Trust department of histology. The total length of the submental island arterial system, the distance from where the facial artery branches off from the carotid to the submental artery perforator entering the anterior belly of digastric or skin, averaged 91.1mm with anaverage facial artery length of 33.1mm and submental artery of 58mm. Vessel diameter for microvascular reconstruction was 1.63mm for the submental artery and 3mm for the facial artery. The most common venous anatomy drainage pattern was the submental island venaecomitantes draining to the retromandibular system then to the internal jugular vein. Almost half the specimens had a dominant superficial submental perforator allowing the ability to raise this as a skin only system. There were generally 2-4 perforators passing through the anterior belly of digastric to supply the skin paddle.73.3% (11/15) of the skeletonised flaps contained no lymph nodes on histological examination. The perforator version of the submental island flap can be safely and consistently raised with inclusion of the anterior belly of digastric. In approximately half the cases a dominant superficial branch allows for a skin only paddle. Due to the vessel diameter, free tissue transfer is predictable.Venous anatomy is variable and care needs to be taken when raising this flap. The skeletonised version of the perforator flap is largely devoid of nodal yield and on oncological review a 16.3% recurrence rate is equivalent to current standard treatment.

Predictors of Cognitive Decline in Healthy Middle-Aged Individuals with Asymptomatic Alzheimer's Disease.

Alzheimer's disease (AD) progresses through a lengthy asymptomatic period during which pathological changes accumulate prior to development of clinical symptoms. As disease-modifying treatments are developed, tools to stratify risk of clinical disease will be required to guide their use. In this study, we examine the relationship of AD biomarkers in healthy middle-aged individuals to health history, family history, and neuropsychological measures and identify cerebrospinal fluid (CSF) biomarkers to stratify risk of progression from asymptomatic to symptomatic AD. CSF from cognitively normal (CN) individuals (N=1149) in the Emory Healthy Brain Study were assayed for Aß42, total Tau (tTau), and phospho181-Tau (pTau), and a subset of 134 cognitively normal, but biomarker-positive, individuals were identified with asymptomatic AD (AsymAD) based on a locally-determined cutoff value for ratio of tTau to Aß42. These AsymAD cases were matched for demographic features with 134 biomarker-negative controls (CN/BM-) and compared for differences in medical comorbidities and family history. Dyslipidemia emerged as a distinguishing feature between AsymAD and CN/BM-groups with significant association with personal and family history of dyslipidemia. A weaker relationship was seen with diabetes, but there was no association with hypertension. Examination of the full cohort by median regression revealed a significant relationship of CSF Aß42 (but not tTau or pTau) with dyslipidemia and diabetes. On neuropsychological tests, CSF Aß42 was not correlated with performance on any measures, but tTau and pTau were strongly correlated with visuospatial perception and visual episodic memory. In addition to traditional CSF AD biomarkers, a panel of AD biomarker peptides derived from integrating brain and CSF proteomes were evaluated using machine learning strategies to identify a set of 8 peptides that accurately classified CN/BM- and symptomatic AD CSF samples with AUC of 0.982. Using these 8 peptides in a low dimensional t-distributed Stochastic Neighbor Embedding analysis and k-Nearest Neighbor (k=5) algorithm, AsymAD cases were stratified into "Control-like" and "AD-like" subgroups based on their proximity to CN/BM- or AD CSF profiles. Independent analysis of these cases using a Joint Mutual Information algorithm selected a set of 5 peptides with 81% accuracy in stratifying cases into AD-like and Control-like subgroups. Performance of both sets of peptides was evaluated and validated in an independent data set from the Alzheimer's Disease Neuroimaging Initiative. Based on our findings, we conclude that there is an important role of lipid metabolism in asymptomatic stages of AD. Visuospatial perception and visual episodic memory may be more sensitive than language-based abilities to earliest stages of cognitive decline in AD. Finally, candidate CSF peptides show promise as next generation biomarkers for predicting progression from asymptomatic to symptomatic stages of AD.

The influence of avoidant attachment and perceived support on disclosure about involvement in donor-assisted conception to family and friends.

STUDY QUESTION: Do the attachment-related dimensions Anxiety and Avoidance and perceived partner and social support in recipients and donors influence disclosure to others about their involvement in donor-assisted conception (DAC)? SUMMARY ANSWER: A higher global score on attachment Avoidance was associated with greater non-disclosure about involvement in DAC by participants to relationship-specific others. WHAT IS KNOWN ALREADY: Within the context of DAC, the topic of disclosure has been investigated in terms of the 'if', 'when', and the 'how' to disclose about circumstances of conception. Less focus, however, has been directed to investigating psychological theoretical frameworks that influence disclosure decisions to others, i.e. to whom information is disclosed and to what extent details are transparently revealed about the donor programme. STUDY DESIGN, SIZE, DURATION: The study was of a cross-sectional design and utilized a sample of 301 participants who were, or had been, involved in DAC, and were recruited across states of Australia. An online self-report questionnaire was completed between June 2014 and June 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: English speaking participants consisting of 209 female recipients and 92 donors (36 sperm; 48 egg; 8 embryo donors). Of the recipients, 104 had successfully conceived children via donated gametes (68 sperm, 23 eggs, 6 embryos, and 7 recipients where both gametes were donated from 2 donors to create the embryo). Participants anonymously completed an online questionnaire consisting of five sections: Demographics, Donor Conception and Disclosure Practices, the Experiences in Close Relationships-Relationships Structure, the Quality of Relationship Inventory, and the Multidimensional Scale of Perceived Social Support. Pearson correlations, independent samples t-tests, Chi-square, and ANOVA were used to explore the association between attachment Anxiety and Avoidance scores and disclosure about involvement in a DAC programme to significant others (i.e. parents, siblings, in-laws, and friends). MAIN RESULTS AND THE ROLE OF CHANCE: Compared to published community cohort data, participants reported lower global scores on attachment Anxiety and Avoidance and high levels of romantic partner and social network support, suggestive of secure relationships in the overall study sample. A higher score on attachment Avoidance was associated with less disclosure to significant others in their social network (i.e. parents, siblings, in-laws, and close friends), even in the presence of strong partner support (partial r = -0.248, P = 0.005). Higher scores on attachment Avoidance were inversely associated with level of perceived partner and social network support (all P < 0.05). Irrespective of attachment scores, more than 90% of all participants agreed that a child born of DAC should be told about mode of conception. LIMITATIONS, REASONS FOR CAUTION: This study utilized a cross-sectional design precluding causal inferences between dimensions of insecure attachment and disclosure practices. Participants were required to self-report on the quality of their relationships with the potential for social desirability respondent bias. The study's self-selecting sample may limit generalization to participants who were dis-inclined to participate. Specifically, respondents who have an Avoidant attachment style, may have elected not to participate in the study. WIDER IMPLICATIONS OF THE FINDINGS: Given the increased use of biotechnology and digital facial recognition enabling self-discovery of the donor and the donor's extended family, non-disclosure about involvement in DAC may have consequences. An 'Avoidant' attachment style is important to assess as a potential risk factor for non-disclosure about involvement in DAC across different relational contexts (e.g. close family members and friends). Fertility counsellors should consider introducing a measure of attachment screening as a pre-emptive psychoeducational strategy during donor implications counselling. This information could be used to offer patients insight into concerns they have about DAC disclosures to key important relationships, providing a target of clinical intervention. STUDY FUNDING/COMPETING INTEREST(S): No external funds were sought for this work. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Structured discharge documentation reduces sex-based disparities in statin prescription in vascular surgery patients.

OBJECTIVE: Perioperative statin use has been shown to improve survival in vascular surgery patients. In 2018, the Northern California Vascular Study Group implemented a quality initiative focused on the use of a SmartText in the discharge summary. We hypothesized that structured discharge documentation would decrease sex-based disparities in evidence-based medical therapy. METHODS: A retrospective analysis was conducted using Vascular Quality Initiative eligible cases at a single institution. Open or endovascular procedures in the abdominal aorta or lower extremity arteries from 2016 to 2021 were included. Bivariate analysis identified factors associated with statin use and sex. Multivariate logistic regression was performed with the end point of statin prescription at discharge and aspirin prescription at discharge. An interaction term assessed the differential impact of the initiative on both sexes. Analysis was then stratified by prior aspirin or statin prescription. An interrupted time series analysis was used to evaluate the trend in statin prescription over time. RESULTS: Overall, 866 patients were included, including 292 (34%) female and 574 (66%) male patients. Before implementation, statins were prescribed in 77% of male and 62% of female patients (P < .01). After implementation, there was no statistically significant difference in statin prescription (91% in male vs 92% in female patients, P = .68). Female patients saw a larger improvement in the adjusted odds of statin prescription compared with male patients (odds ratio: 3.1, 95% confidence interval: 1.1-8.6, P = .04). For patients not prescribed a statin preoperatively, female patients again saw an even larger improvement in the odds of being prescribed a statin at discharge (odds ratio: 6.4, 95% confidence interval: 1.8-22.7, P < .01). Interrupted time series analysis demonstrated a sustained improvement in the frequency of prescription for both sexes over time. The unadjusted frequency of aspirin prescription also improved by 3.5% in male patients vs 5.5% in female patients. For patients not prescribed an aspirin preoperatively, we found that the frequency of aspirin prescription significantly improved for both male (19% increase, P = .006) and female (31% increase, P = .001) patients. There was no significant difference in the perioperative outcomes between male and female patients before and after standardized discharge documentation. CONCLUSIONS: A simple, low-cost regional quality improvement initiative eliminated sex-based disparities in statin prescription at a single institution. These findings highlight the meaningful impact of regional quality improvement projects. Future studies should examine the potential for structured discharge documentation to improve patient outcomes and reduce disparities.

Systematic Review and Meta-Analysis of Cardiovascular Consequences of Myocardial Bridging in Hypertrophic Cardiomyopathy.

Myocardial bridging (MB) is a congenital variant in which a segment of a coronary artery follows an atypical intramural course under a "bridge" of myocardium and is notably common in hypertrophic cardiomyopathy (HCM). This systematic review and meta-analysis explored the clinical consequences of MB in patients with HCM. A total of 3 outcome domains were investigated: cardiovascular mortality, nonfatal adverse cardiac events, and investigative indicators of myocardial ischemia. A meta-analysis was performed on 10 observational studies comparing outcomes in patients with HCM with and without MB. Studies were identified through a systematic search of 4 databases (PubMed, Scopus, Medline Complete, and Web of Science). The quality of the studies was assessed using a modified version of the Downs and Black tool, from which studies could score a maximum of 23 points. The mean score was 17.5 ± 1.3 (good). The meta-analysis showed that MB was not associated with cardiovascular mortality (odds ratio [OR] 1.70, 95% confidence interval [CI] 0.56 to 5.15, p = 0.35) or nonfatal adverse cardiac events (OR 1.80, 95% CI 0.98 to 3.28, p = 0.06) but was associated with myocardial ischemia (OR 1.89, 95% CI 1.03 to 3.44, p = 0.04). In conclusion, the potential prognostic implications of MB in HCM, especially in those with hemodynamically significant bridges and/or severe underlying disease, should not be ignored. The focus of future studies should be to establish functional and morphologic thresholds, by which MB may adversely influence prognosis by corroborating imaging findings with clinical outcome data.

Racial and ethnic disparities in major adverse limb events persist for chronic limb threatening ischemia despite presenting limb threat severity after peripheral vascular intervention.

OBJECTIVE: Racial and ethnic disparities have been well-documented in the outcomes for chronic limb threatening ischemia (CLTI). One purported explanation has been the disease severity at presentation. We hypothesized that the disparities in major adverse limb events (MALE) after peripheral vascular intervention (PVI) for CLTI would persist despite controlling for disease severity at presentation using the WIfI (Wound, Ischemia, foot Infection) stage. METHODS: The Vascular Quality Initiative PVI dataset (2016-2021) was queried for CLTI. Patients were excluded if they were missing the WIfI stage. The primary end point was the incidence of 1-year MALE, defined as major amputation (through the tibia or fibula or more proximally) or reintervention (endovascular or surgical) of the initial treatment limb. A multivariate hierarchical Fine-Gray analysis was performed, controlling for hospital variation, competing risk of death, and presenting WIfI stage, to assess the independent association of Black/African American race and Latinx/Hispanic ethnicity with MALE. A Cox proportional hazard regression model was used for the 1-year survival analysis. RESULTS: Overall, 47,830 patients (60%) had had WIfI scores reported (73% White, 20% Black, and 7% Latinx). The 1-year unadjusted cumulative incidence of MALE was 13.1% (95% confidence interval [CI], 12.6%-13.5%) for White, 14.3% (95% CI, 13.5%-15.3%) for Black, and 17.0% (95% CI, 15.3%-18.9%) for Latinx patients. On bivariate analysis, the occurrence of MALE was significantly associated with younger age, Black race, Latinx ethnicity, coronary artery disease, cerebrovascular disease, congestive heart failure, hypertension, diabetes, dialysis, intervention level, any prior minor or major amputation, and WIfI stage (P < .001). The cumulative incidence of 1-year MALE increased by increasing WIfI stage: stage 1, 11.7% (95% CI, 10.9%-12.4%); stage 2, 12.4% (95% CI, 11.8%-13.0%); stage 3, 14.8% (95% CI, 13.8%-15.8%); and stage 4, 15.4% (95% CI, 14.3%-16.6%). The cumulative incidence also increased by intervention level: inflow, 10.7% (95% CI, 9.8%-11.7%), femoropopliteal, 12.3% (95% CI, 11.7%-12.9%); and infrapopliteal, 14.1% (95% CI, 13.5%-14.8%). After adjustment for WIfI stage only, Black race (subdistribution hazard ratio [SHR], 1.30; 95% CI, 1.17-1.44; P < .001) and Latinx ethnicity (SHR, 1.58; 95% CI, 1.37-1.81; P < .001) were associated with an increased 1-year hazard of MALE compared with White race. On adjusted multivariable analysis, MALE disparities persisted for Black/African American race (SHR, 1.12; 95% CI, 1.01-1.25; P = .028) and Latinx/Hispanic ethnicity (SHR, 1.34; 95% CI, 1.16-1.54; P < .001) compared with White race. CONCLUSIONS: Black/African American and Latinx/Hispanic patients had a higher associated hazard of MALE after PVI for CLTI compared with White patients despite an adjustment for WIfI stage at presentation. These results suggest that disease severity at presentation does not account for disparities in outcomes. Further work should focus on better understanding the underlying mechanisms for disparities in historically marginalized racial and ethnic groups presenting with CLTI.

Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42-0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries.

Background: Immunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination. Aim: We studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries. Materials and methods: From a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups. Results: Geometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies > 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year. Conclusions: An aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.

Anatomy Nights: An international public engagement event increases audience knowledge of brain anatomy.

Anatomy Nights is an international public engagement event created to bring anatomy and anatomists back to public spaces with the goal of increasing the public's understanding of their own anatomy by comparison with non-human tissues. The event consists of a 30-minute mini-lecture on the anatomy of a specific anatomical organ followed by a dissection of animal tissues to demonstrate the same organ anatomy. Before and after the lecture and dissection, participants complete research surveys designed to assess prior knowledge and knowledge gained as a result of participation in the event, respectively. This study reports the results of Anatomy Nights brain events held at four different venues in the UK and USA in 2018 and 2019. Two general questions were asked of the data: 1) Do participant post-event test scores differ from pre-event scores; and 2) Are there differences in participant scores based on location, educational background, and career. We addressed these questions using a combination of generalized linear models (R's glm function; R version 4.1.0 [R Core Team, 2014]) that assumed a binomial distribution and implemented a logit link function, as well as likelihood estimates to compare models. Survey data from 91 participants indicate that scores improve on post-event tests compared to pre-event tests, and these results hold irrespective of location, educational background, and career. In the pre-event tests, participants performed well on naming structures with an English name (frontal lobe and brainstem), and showed signs of improvement on other anatomical names in the post-test. Despite this improvement in knowledge, we found no evidence that participation in Anatomy Nights improved participants' ability to apply this knowledge to neuroanatomical contexts (e.g., stroke).

The seasonal relationships between household dietary diversity and child growth in a rural Timor-Leste community.

Both child growth and dietary diversity are poor in rural Timor-Leste. The rainy season is associated with food scarcity, yet the association between seasonal scarcity, food diversity, and child growth is underdocumented. This study assesses the relationship between household dietary diversity and children's standardized growth across the 2018 food-scarce (April-May; post-rainy period) and post-harvest (October) seasons in the agricultural community of Natarbora, on the south-coastal plains of Timor-Leste. We conducted household interviews and collected anthropometric data across 98 and 93 households in the post-rainy and post-harvest periods, respectively. Consumed household foods were obtained via 24-h diet recalls and were subsequently categorized into a nine-food-group dietary diversity score (DDS; number of different food groups consumed). The DDS was related to children's standardized short-term growth (z-weight, z-body mass index [BMI] and percent change in weight over the harvest season) via linear mixed models. Across seasons, DDS increased from 3.9 (standard deviation [SD] = 1.0) to 4.3 (SD = 1.4; p < 0.05). In the post-rainy season, children in high DDS households had higher z-weight than those in low DDS households and higher z-BMI than children in medium and low DDS households. In the post-harvest period, household DDS did not predict children's z-weight but predicted z-BMI. Consumption of protein-rich foods, particularly animal-source foods and legumes, in low- and medium-DDS households may be associated with improved child growth. While consuming more animal-source foods in the post-rainy season would be ideal, promoting the consumption of locally grown legumes, such as beans and pulses, may facilitate better nutritional outcomes for more children in rural Timor-Leste.

Risk factors for venous thromboembolism after vascular surgery and implications for chemoprophylaxis strategies.

OBJECTIVE: Venous thromboembolism (VTE) is an important cause of postoperative morbidity and mortality. However, the reported incidence after major vascular surgery has ranged from as low as 1% to >10%. Furthermore, little is known about optimal chemoprophylaxis regimens or rates of postdischarge VTE in this population. In the present study, we aimed to better characterize the rates of in-hospital and postdischarge VTE after major vascular surgery, the role of chemoprophylaxis timing, and the association of VTE with mortality. METHODS: A single-center retrospective study of 1449 major vascular operations (2013-2020) was performed and included 189 endovascular abdominal aortic aneurysm repairs (13%), 169 thoracic endovascular aortic aneurysm repairs (12%), 318 open aortic operations (22%), 640 lower extremity bypasses (44%), and 133 femoral endarterectomies (9%). The baseline characteristics, anticoagulant and antiplatelet medications, and outcomes were abstracted from an electronic database with medical record auditing. Postoperative VTE (pulmonary embolism and deep vein thrombosis) within 90 days of surgery was classified by the location, symptoms, and treatment. A cut point analysis using Youden's index identified the most VTE discriminating timing of chemoprophylaxis (including therapeutic vs prophylactic anticoagulant and antiplatelet medications) and Caprini score. Multivariable logistic regression was used to test the association of VTE with chemoprophylaxis timing, Caprini score, and additional risk factors. Cox proportional hazard modeling was used to measure the association between VTE and mortality. RESULTS: The overall VTE incidence was 3.4% (65% deep vein thrombosis; 25% pulmonary embolism; 10% both), and 37% had occurred after discharge. The rate of symptomatic VTE was 2.4%, which was lowest for endovascular abdominal aortic aneurysm repair (0.0%) and highest for open aortic surgery (4.1%; P = .02). Those who had developed VTE had had a longer length of stay, higher rates of end-stage renal disease and prior VTE, and higher Caprini scores (8 vs 5 points; P < .01 for all). Those who had developed VTE were also more likely to have received ≥2 U of blood postoperatively, required an unplanned return to the operating room, had delayed chemoprophylaxis, anticoagulation, and/or antiplatelet initiation of >4 days postoperatively, and had increased 90-day mortality (P < .01 for all). A Caprini score of ≥7 (29% of patients) was associated with postdischarge VTE (2.6% vs 0.7%; P = .01), and chemoprophylaxis, anticoagulation, and antiplatelet timing of >4 days was associated with an increased adjusted odds of VTE (odds ratio, 2.4; 95% confidence interval, 1.1-4.9). Although no fatal VTEs were identified, VTE was an independent predictor of 90-day mortality (adjusted hazard ratio, 2.7; 95% confidence interval, 1.3-5.9). CONCLUSIONS: These data have shown that patients undergoing major vascular surgery are particularly prone to the development of VTE, with frequent hypercoagulable comorbidities. The earlier initiation of chemoprophylaxis was associated with a reduced risk of VTE development. Furthermore, the postdischarge VTE rates might reach thresholds warranting postdischarge chemoprophylaxis, especially for patients with a Caprini score of ≥7.

A new classification system for the anatomical variations of the human circle of Willis: A systematic review.

The circle of Willis (CoW) is an anastomotic arterial network located on the base of the brain. Studies have shown that it demonstrates considerable anatomical variation in humans. This systematic review aimed to identify and catalogue the described anatomical variations of the CoW in humans to create a new, comprehensive variation classification system. An electronic literature search of five databases identified 5899 studies. A two-phase screening process was performed, and studies underwent quality assessment. A total of 42 studies were included in the review. Data were extracted and circles were reconstructed digitally using graphics software. The classification system contains 82 CoW variations in five continuous groups. Group one contains 24 circles with one or more hypoplastic segments only. Group two contains 11 circles with one or more absent segments only. Group three contains 6 circles with hypoplastic and absent segments only. Group four contains 26 circles with one or more accessory segments. Group five contains 15 circles with other types of anatomical variation. Within each group, circles were subcategorised according to the number or type of segments affected. An original coding system was created to simplify the description of anatomical variations of the CoW. The new classification system provides a comprehensive ontology of the described anatomical variations of the CoW in humans. When used with the coding system, it allows the description and categorisation of recorded and unrecorded variants identified in past and future studies. It is applicable to current clinical practice and the anatomical community, including human anatomy education and research.

Endovascular treatment of high-risk peripheral vascular occlusive lesions: a review of current evidence and emerging applications of intravascular lithotripsy, atherectomy, and paclitaxel-coated devices.

Endovascular treatment of peripheral arterial disease has evolved and expanded rapidly over the last 20 years. New technologies have increased the diversity of devices available and have made it possible to approach even the most challenging and high-risk lesions using endovascular techniques. In this review, we examine the clinical evidence available for several categories of endovascular devices available to treat peripheral arterial disease, including intravascular lithotripsy, atherectomy, and drug-coated devices. The best application for some technologies, such as intravascular lithotripsy and atherectomies, have yet to be identified. In contrast, drug-coated devices have an established role in patients at high risk for long-term failure, but have been the subject of much controversy, given recent concerns about possible adverse effects of paclitaxel. Future investigation should further assess these technologies in patients with complex disease using updated staging systems and outcomes with direct clinical relevance, such as functional improvement, wound healing, and freedom from recurrent symptoms.

Pandemics, Protests, and Pronouns: The Changing Landscape of Biomedical Visualisation and Education.

Events in early 2020 changed the landscape of education for the foreseeable future, perhaps permanently. Three events had a significant impact; (1) the Coronavirus disease 2019 (COVID-19) pandemic, (2) the death of George Floyd, which resulted in the most recent Black Lives Matter (BLM) protests, and (3) the Twitter storm, the resultant societal fallout and freedom of speech campaigns, following comments made by author JK Rowling which many deemed transphobic. These events had a differential impact on biomedical sciences, when compared to other sectors. COVID-19 resulted in a global lockdown, with higher education institutions closing campuses and moving to online-only delivery. This rapid change required radical shifts in the use of technology, with mass delivery of teaching at short notice. The BLM protests further raised awareness of the inequalities within society, particularly those experienced by Black people and other oppressed groups. As a result, there have been calls for the decolonisation of the curriculum. The implications of these three key events have led institutions to rethink their policies, teaching delivery, assessment, curricula, and physical environments. This chapter considers (1) the implications of a swift change in the primary mode of curriculum delivery within Higher Education to online formats and (2) how recent adverse events have resulted in calls for much-needed changes in visual representations within biomedical sciences. Finally, we consider (3) the role of the hidden curriculum and the potential impact of visual representations in curricula on the delivery of healthcare and the fight against health inequalities, which are often as a result of implicit biases. The year 2020 has proven timely in presenting the opportunity for change, provided through the power of imagery.

Understanding value and patient complexity among common inpatient vascular surgery procedures.

OBJECTIVE: Vascular surgery patients are highly complex, second only to patients undergoing cardiac procedures. However, unlike cardiac surgery, work relative value units (wRVU) for vascular surgery were undervalued based on an overall patient complexity score. This study assesses the correlation of patient complexity with wRVUs for the most commonly performed inpatient vascular surgery procedures. METHODS: The 2014 to 2017 National Surgical Quality Improvement Program Participant Use Data Files were queried for inpatient cases performed by vascular surgeons. A previously developed patient complexity score using perioperative domains was calculated based on patient age, American Society of Anesthesiologists class of ≥4, major comorbidities, emergent status, concurrent procedures, additional procedures, hospital length of stay, nonhome discharge, and 30-day major complications, readmissions, and mortality. Procedures were assigned points based on their relative rank and then an overall score was created by summing the total points. An observed to expected ratio (O/E) was calculated using open ruptured abdominal aortic aneurysm repair (rOAAA) as the referent and then applied to an adjusted median wRVU per operative minute. RESULTS: Among 164,370 cases, patient complexity was greatest for rOAAA (complexity score = 128) and the least for carotid endarterectomy (CEA) (complexity score = 29). Patients undergoing rOAAA repair had the greatest proportion of American Society of Anesthesiologists class of ≥IV (84.8%; 95% confidence interval [CI], 82.6%-86.8%), highest mortality (35.5%; 95% CI, 32.8%-38.3%), and major complication rate (87.1%; 95% CI, 85.1%-89.0%). Patients undergoing CEA had the lowest mortality (0.7%; 95% CI, 0.7%-0.8%), major complication rate (8.2%; 95% 95% CI, 8.0%-8.5%), and shortest length of stay (2.7 days; 95% CI, 2.7-2.7). The median wRVU ranged from 10.0 to 42.1 and only weakly correlated with overall complexity (Spearman's ρ = 0.11; P < .01). The median wRVU per operative minute was greatest for thoracic endovascular aortic repair (0.25) and lowest for both axillary-femoral artery bypass (0.12) and open femoral endarterectomy, thromboembolectomy, or reconstruction (0.12). After adjusting for patient complexity, CEA (O/E = 3.8) and transcarotid artery revascularization (O/E = 2.8) had greater than expected O/E. In contrast, lower extremity bypass (O/E = 0.77), lower extremity embolectomy (O/E = 0.79), and open abdominal aortic repair (O/E = 0.80) had a lower than expected O/E. CONCLUSIONS: Patient complexity varies substantially across vascular procedures and is not captured effectively by wRVUs. Increased operative time for open procedures is not adequately accounted for by wRVUs, which may unfairly penalize surgeons who perform complex open operations.

Anatomical variations of the circle of Willis and their prevalence, with a focus on the posterior communicating artery: A literature review and meta-analysis.

The circle of Willis is an anastomotic network of arteries surrounding the base of the brain, providing collateral circulation to prevent ischemia. It has, however, long been established that it exhibits considerable anatomical variation when compared to Thomas Willis' originally described circle. This study aimed primarily to determine an accurate prevalence of the variation of the circle of Willis in the general population and the prevalence of common posterior communicating artery variations. Additional aims were to explain why such a wide range of reported variations exist, and whether different types of studies report significantly different prevalence of variation. A comprehensive literature search identified 764 papers. A three-phase screening process was undertaken, involving a critical analysis of papers, and a total of 33 papers were selected for analysis and literature review. A descriptive statistics test with bootstrap was performed to estimate the average prevalence of variations. The estimated prevalence of general variation, unilateral, and bilateral posterior communicating artery hypoplasia or aplasia was 68.22 ± 14.32%, 19.45 ± 8.63%, and 22.83 ± 14.58%, respectively. Over half of the population exhibit a circle of Willis with some form of variation. To provide a more accurate estimation for the prevalence of variations, a universal classification system needs to be established, collating all the work from high-quality studies, to provide a comprehensive database of the circle's variations. Knowing the prevalence of variations and how they can impact neurosurgical approaches or patterns of ischemic pathology can be crucial in providing effective patient care.

Clay-Based Modeling in the Anatomist's Toolkit: A Systematic Review.

Anatomical education has suffered from reduced teaching time and poor availability of staff and resources over the past thirty years. Clay-based modeling (CBM) is an alternative technique for teaching anatomy that can improve student knowledge and experience. This systematic review aimed to summarize and appraise the quality of the literature describing the uses, advantages, and limitations of CBM compared to alternative methods of teaching human gross anatomy to students or qualified healthcare professionals. A systematic search of Embase, MEDLINE, Scopus, and Web of Science databases was conducted, and the Medical Education Research Quality Instrument (MERSQI) was used to assess study quality. Out of the 829 studies identified, 12 papers met the inclusion criteria and were eligible for this review. The studies were of high quality, with a mean MERSQI score of 11.50/18. Clay-based modeling can be used to teach all gross anatomical regions, and 11 studies demonstrated a significant improvement in short-term knowledge gain in students who used CBM in comparison to other methods of learning anatomy. Eight studies that included subjective assessment showed that CBM is rated highly. However, some studies showed that students viewed CBM as juvenile and experienced difficulty making the models. Additionally, there is no evidence to suggest that CBM improves long-term knowledge. Clay-based modeling is an effective learning method for human gross anatomy and should be incorporated into the anatomists' toolkit. In the future, more randomized controlled studies with transparent study designs investigating the long-term impact of CBM are needed.