Ebola virus antibody decay-stimulation in a high proportion of survivors.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1-3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

BACKGROUND: One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. METHODS: We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. RESULTS: In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. CONCLUSIONS: The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID).

BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets (COS) has been developed. COS, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. METHODS: Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. RESULTS: The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents) 15 questions were eliminated, and 11 further questions were eliminated after round 2 (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: death at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, five year survival, and continued sac growth. CONCLUSION: Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and to define instruments for cognitive functioning is needed.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Overparenting and psychological wellbeing among Chinese adolescents: Findings based on latent growth modeling.

Although overparenting is a growing phenomenon across the globe, there is a severe lack of longitudinal studies examining the trajectory of overparenting and its effects on early adolescent development, particularly in non-Western contexts. The study collected three waves of longitudinal data from 1328 early Chinese adolescents in Hong Kong with an interval of 1 year to examine the stability and change of perceived paternal and maternal overparenting and their effects on adolescent psychological wellbeing. The results indicated that perceived paternal and maternal overparenting declined over time. Besides, adolescents reported lower anxiety and depressive symptoms when they perceived a steep decline in maternal overparenting. Adolescent anxiety at earlier time points also predicted a steeper decline in paternal and maternal overparenting trajectories respectively. Furthermore, we identified gender differences in the initial level of paternal overparenting and the trajectory of maternal overparenting, as well as the effects of rates of change of maternal overparenting on adolescent anxiety and depressive symptoms. The findings give support for self-determination theory and the separation-individuation model, suggesting that changes of overparenting may hinder adolescents' desires for autonomy and self-direction, which may increase their psychological morbidity. The study contributes to theoretical development of contemporary Chinese socialization models and provides useful pointers for future studies of overparenting.

Pathogenesis and management of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

The Fragility of Statistical Findings in Cervical Disc Arthroplasty: a Systematic Review of Randomized Controlled Trials.

PURPOSE: This study employs both the fragility index (FI) and fragility quotient (FQ) to assess the level of robustness in the cervical disc arthroplasty (CDA) literature. We hypothesize that dichotomous outcomes involving CDA would exhibit statistical vulnerability. METHODS: A PubMed search was conducted to evaluate dichotomous data for randomized controlled trials (RCTs) in CDA literature from 2000 to 2023. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 1561 articles screened, 111 met the search criteria, with 35 RCTs evaluating CDA included for analysis. Six hundred and ninety-three outcome events with 130 significant (P < 0.05) outcomes and 563 nonsignificant (P ≥ 0.05) outcomes were identified. The overall FI and FQ for all 693 outcomes were 5 (IQR 3-7) and 0.019 (IQR 0.011-0.043). Fragility analysis of statistically significant outcomes and nonsignificant outcomes both revealed an FI of 5. All of the studies reported loss to follow-up (LTF) data where 65.7% (23) did not report or reported an LTF greater or equal to 5. CONCLUSIONS: The literature regarding CDA RCTs lacks statistical robustness and may misrepresent the conclusions with the sole use of the P value. By implementing the FI and FQ along with the P value, we believe the interpretation and contextualization of the clinical data surrounding CDA will be better understood.

Incremental Contribution of the Minnesota Multiphasic Personality Inventory - 3 to Predicting One-Year Postoperative Spinal Cord Surgery/Spinal Cord Stimulation Outcomes.

Pre-surgical psychological assessments are becoming common in the United States and are recommended or required prior to surgical/spinal cord stimulator intervention for chronic back pain. Psychological testing is often recommended for these evaluations and the various versions of the Minnesota Multiphasic Personality Inventory (MMPI) have demonstrated utility for predicting outcomes in this setting. This investigation sought to extend that literature with the newest version of the MMPI, the MMPI-3. The sample comprised of 909 patients (50.5% men, 49.5% women) who consented to participating in an outcome study and took the MMPI-3 along with other self-report measures of pain, functional disability, and emotional functioning prior to surgery as part of their pre-surgical psychological assessment. Self-report measures of pain, functional disability, and emotional functioning were administered again one-year following the intervention. MMPI-3 scale scores accounted for up to 9% of additional variance in the outcomes after controlling for pre-surgical measures. Measures of emotional/internalizing dysfunction, somatic dysfunction, and, to a lesser extent, behavioral/externalizing dysfunction contributed the most to the prediction of poorer outcomes.

The mediating roles of the oral microbiome in saliva and subgingival sites between e-cigarette smoking and gingival inflammation.

BACKGROUND: Electronic cigarettes (ECs) have been widely used by young individuals in the U.S. while being considered less harmful than conventional tobacco cigarettes. However, ECs have increasingly been regarded as a health risk, producing detrimental chemicals that may cause, combined with poor oral hygiene, substantial inflammation in gingival and subgingival sites. In this paper, we first report that EC smoking significantly increases the odds of gingival inflammation. Then, through mediation analysis, we seek to identify and explain the mechanism that underlies the relationship between EC smoking and gingival inflammation via the oral microbiome. METHODS: We collected saliva and subgingival samples from 75 EC users and 75 non-users between 18 and 34 years in age and profiled their microbial compositions via 16S rRNA amplicon sequencing. We conducted raw sequence data processing, denoising and taxonomic annotations using QIIME2 based on the expanded human oral microbiome database (eHOMD). We then created functional annotations (i.e., KEGG pathways) using PICRUSt2. RESULTS: We found significant increases in α-diversity for EC users and disparities in ß-diversity between EC users and non-users. We also found significant disparities between EC users and non-users in the relative abundance of 36 microbial taxa in the saliva site and 71 microbial taxa in the subgingival site. Finally, we found that 1 microbial taxon in the saliva site and 18 microbial taxa in the subgingival site significantly mediated the effects of EC smoking on gingival inflammation. The mediators on the genus level, for example, include Actinomyces, Rothia, Neisseria, and Enterococcus in the subgingival site. In addition, we report significant disparities between EC users and non-users in the relative abundance of 71 KEGG pathways in the subgingival site. CONCLUSIONS: These findings reveal that continued EC use can further increase microbial dysbiosis that may lead to periodontal disease. Our findings also suggest that continued surveillance for the effect of ECs on the oral microbiome and its transmission to oral diseases is needed.

Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results.

PURPOSE: To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab. DESIGN: Single-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes. METHODS: Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes. MAIN OUTCOME MEASURES: The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP). RESULTS: One hundred ninety-four participants (225 eligible eyes) were randomized to dexamethasone (n = 65 participants and 77 eyes), methotrexate (n = 65 participants and 79 eyes), or ranibizumab (n = 64 participants and 69 eyes). All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35%, 11%, and 22% for dexamethasone, methotrexate, and ranibizumab, respectively. Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P < 0.01) or ranibizumab (P = 0.018). Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001). Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME. CONCLUSIONS: At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sex-specific differences in the standard of care for infrarenal abdominal aortic aneurysm repair, and risk of major adverse cardiovascular events and death.

BACKGROUND: This study investigated whether sex-specific differences in preoperative/perioperative standard of care (SOC) account for disparity in outcomes after elective infrarenal abdominal aortic aneurysm repair. METHODS: This was a retrospective cohort study of elective infrarenal abdominal aortic aneurysm repairs (2013-2020) using depersonalized patient-level National Vascular Registry data. SOC was defined for waiting times, preoperative assessment (multidisciplinary/anaesthetic review), cardiovascular risk prevention, and perioperative medication. The primary outcome was major cardiovascular event and/or death (MACED). RESULTS: Some 21 810 patients with an infrarenal abdominal aortic aneurysm were included, 2380 women and 19 430 men. Women less often underwent aneurysm repair within SOC waiting times (51.5 versus 59.3 per cent; P < 0.001), but were equally likely to receive preoperative assessment (72.1 versus 72.5 per cent; P = 0.742). Women were less likely to receive secondary prevention for known cardiac disease (34.9 versus 39.6 per cent; P = 0.015), but more often met overall cardiovascular risk prevention standards (52.1 versus 47.3 per cent; P < 0.001). Women were at greater risk of MACED (open: 12.0 versus 8.9 per cent, P < 0.001; endovascular: 4.9 versus 2.9 per cent, P < 0.001; risk-adjusted OR 1.33, 95 per cent c.i. 1.12 to 1.59). A significant reduction in the odds of MACED was associated with preoperative assessment (OR 0.86, 0.75 to 0.98) and SOC waiting times (OR 0.78, 0.69 to 0.87). There was insufficient evidence to confirm a significant sex-specific difference in the effect of SOC preoperative assessment (women: OR 0.69, 0.50 to 0.97; men: OR 0.89, 0.77 to 1.03; interaction P = 0.170) or SOC waiting times (women: OR 0.84, 0.62 to 1.16; men: OR 0.76, 0.67 to 0.87; interaction P = 0.570) on the risk of MACED. CONCLUSION: SOC waiting times and preoperative assessment were not met for both sexes, which was associated with an increased risk of MACED. Sex-specific differences in SOC attenuated but did not fully account for the increased risk of MACED in women.

Shifts in the composition and distribution of Pacific Arctic larval fish assemblages in response to rapid ecosystem change.

The Pacific Arctic marine ecosystem has undergone rapid changes in recent years due to ocean warming, sea ice loss, and increased northward transport of Pacific-origin waters into the Arctic. These climate-mediated changes have been linked to range shifts of juvenile and adult subarctic (boreal) and Arctic fish populations, though it is unclear whether distributional changes are also occurring during the early life stages. We analyzed larval fish abundance and distribution data sampled in late summer from 2010 to 2019 in two interconnected Pacific Arctic ecosystems: the northern Bering Sea and Chukchi Sea, to determine whether recent warming and loss of sea ice has restricted habitat for Arctic species and altered larval fish assemblage composition from Arctic- to boreal-associated taxa. Multivariate analyses revealed the presence of three distinct multi-species assemblages across all years: (1) a boreal assemblage dominated by yellowfin sole (Limanda aspera), capelin (Mallotus catervarius), and walleye pollock (Gadus chalcogrammus); (2) an Arctic assemblage composed of Arctic cod (Boreogadus saida) and other common Arctic species; and (3) a mixed assemblage composed of the dominant species from the other two assemblages. We found that the wind- and current-driven northward advection of warmer, subarctic waters and the unprecedented low-ice conditions observed in the northern Bering and Chukchi seas beginning in 2017 and persisting into 2018 and 2019 have precipitated community-wide shifts, with the boreal larval fish assemblage expanding northward and offshore and the Arctic assemblage retreating poleward. We conclude that Arctic warming is most significantly driving changes in abundance at the leading and trailing edges of the Chukchi Sea larval fish community as boreal species increase in abundance and Arctic species decline. Our analyses document how quickly larval fish assemblages respond to environmental change and reveal that the impacts of Arctic borealization on fish community composition spans multiple life stages over large spatial scales.

A systematic review from basics to omics on bacteriophage applications in poultry production and processing.

The growing human population is currently facing an unprecedented challenge on global food production and sustainability. Despite recognizing poultry as one of the most successful and rapidly growing food industries to address this challenge; poultry health and safety remain major issues that entail immediate attention. Bacterial diseases including colibacillosis, salmonellosis, and necrotic enteritis have become increasingly prevalent during poultry production. Likewise, outbreaks caused by consumption of undercooked poultry products contaminated with zoonotic bacterial pathogens such as Salmonella, Campylobacter and Listeria, are a serious public health concern. With antimicrobial resistance problem and restricted use of antibiotics in food producing animals, bacteriophages are increasingly recognized as an attractive natural antibacterial alternative. Bacteriophages have recently shown promising results to treat diseases in poultry, reduce contamination of carcasses, and enhance the safety of poultry products. Omics technologies have been successfully employed to accurately characterize bacteriophages and their genes/proteins important for interaction with bacterial hosts. In this review, the potential of using lytic bacteriophages to mitigate the risk of major poultry-associated bacterial pathogens are explored. This study also explores challenges associated with the adoption of this technology by industries. Furthermore, the impact of omics approaches on studying bacteriophages, their host interaction and applications is discussed.

Shared Decision Making and the Management of Intact Abdominal Aortic Aneurysm: A Scoping Review of the Literature.

OBJECTIVE: The aim of this study was to summarise the current knowledge of shared decision making (SDM) in patients facing a treatment decision about an intact abdominal aortic aneurysm (AAA), and to identify where further evidence is needed. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched on 18 July 2021. An updated search was run on 31 May 2022 for relevant studies published from 1 January 2000 to 31 May 2022. REVIEW METHODS: This scoping review was undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines following a pre-defined protocol, retrieving studies reporting on aspects of SDM in those with intact AAAs. Qualitative synthesis of the articles was performed, and the results grouped according to theme. RESULTS: Fifteen articles reporting on a total of 1 344 participants (age range 62-74 years) from hospital vascular surgery clinics with intact AAAs were included. Studies were observational (n = 9), non-randomised studies of an intervention (n = 3), and randomised clinical trials (n = 3). The first theme was the preferences and practice of SDM. The proportion of patients preferring SDM ranged from 58% to 95% (three studies), although objective rating of SDM practice was consistently < 50% (three studies). Clinician training improved SDM practice. The second theme was poor provision of information. Fewer than half of patients (0 - 46%) surveyed were informed about all available treatment options (three studies). Publicly available information sources were rated as poor. The third theme concerned the utility of decision making support tools (DSTs). Two randomised trials demonstrated that the provision of DSTs improves patient knowledge and agreement between patient preference and repair type received but not objective measures of SDM for patients with AAAs. CONCLUSION: SDM for patients with an intact AAA appears to be in its infancy. Most patients with an AAA want SDM, but this is not commonly applied. Most patients with an AAA do not receive adequate information for SDM, although the use of bespoke DSTs leaves patients better informed to facilitate SDM.

Dual-mode colorimetric/fluorescent chemosensor for Cu2+/Zn2+ and fingerprint imaging based on rhodamine ethylenediamine bis(triazolyl silsesquioxane).

A novel dual functional and visual rhodamine ethylenediamine bis(triazolyl silsesquioxane) (RBS) chemosensor was successfully synthesized using "click" chemistry. The results have unambiguously demonstrated that RBS can act in fluorescent and colorimetric sensing of Cu2+ and Zn2+ by their respective coordination with triazole structures and, more importantly, it has also been found that triazole-amide of RBS could turn on chelation-enhanced fluorescence (CHEF) of Cu2+. Remarkably, the addition of Cu2+ triggered an enhanced fluorescent emission by 63.3-fold (ϕF = 0.41), while Zn2+ enhanced it 48.3-fold (ϕF = 0.29) relative to the original RBS (ϕF = 0.006) in acetonitrile (MeCN) solvent. The fluorescent limit of detection for Cu2+ and Zn2+ is similar and fall within 3.0 nM, while under colorimetric sensing the responses were 2.14 × 10-8 and 4.0 × 10-8 mol L-1, respectively. Moreover, the effective sensing profile of RBS and extended applications of RBS-Cu2+ and RBS-Zn2+ for fingerprinting detection and imaging were observed with adequate sensitivity, stability and legibility under the dual visual responses.

Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative Losartan Effects on Emphysema Progression Clinical Trial.

Rationale: There are no pharmacologic agents that modify emphysema progression in patients with chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of losartan, an angiotensin receptor blocker, to reduce emphysema progression. Methods: The trial was a multicenter, randomized, placebo-controlled trial conducted between May 2017 and January 2021. Eligible participants were aged ⩾40 years, had moderate to severe airflow obstruction, ⩾10 pack-years of smoking, mild-moderate emphysema on high-resolution computed tomography, and no medical indication for or intolerance of angiotensin receptor blockers. Treatment with losartan 100 mg daily or matching placebo (1:1) was randomly assigned. The primary outcome was emphysema progression on high-resolution computed tomography over 48 weeks. Secondary outcomes included the St George's Respiratory Questionnaire, the modified Medical Research Council dyspnea scale, the COPD Assessment Test, and the Physical Function-Short Form 20a. Measurements and Main Results: A total of 220 participants were enrolled; 58% were men, 19% were African American, and 24% were current smokers. The medians (interquartile ranges) for age were 65 (61-73) years and 48 (36-59) for percent predicted FEV1 after bronchodilator use. The mean (95% confidence interval) percentage emphysema progression was 1.35% (0.67-2.03) in the losartan group versus 0.66% (0.09-1.23) in the placebo group (P = NS). Conclusions: Losartan did not prevent emphysema progression in people with COPD with mild-moderate emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT02696564).

The Statistical Fragility of Orbital Fractures: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The P value has often been used as a tool to determine the statistical significance and evaluate the statistical robustness of study findings in orthopedic literature. The purpose of this study is to apply both the fragility index (FI) and the fragility quotient (FQ) to evaluate the degree of statistical fragility in orbital fracture literature. We hypothesized that the dichotomous outcomes within the orbital fracture literature will be vulnerable to a small number of outcome event reversals and will be statistically fragile. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the authors identified all dichotomous data for randomized controlled trials (RCTs) in orbital fracture literature and performed a PubMed search from 2000 to 2022. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each FI by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 3,329 studies screened, 28 met the criteria with 10 RCTs evaluating orbital fractures included for analysis. A total of 58 outcome events with 22 significant (P < .05) outcomes and 36 nonsignificant (P ≥ .05) outcomes were identified. The overall FI and FQ for all 58 outcomes was 5 (IQR: 4 to 5) and 0.140 (IQR: 0.075 to 0.250), respectively. Fragility analysis of statistical significant outcomes and nonsignificant outcomes had an FI of 3.5 with no IQR and 5 (IQR 4-5), respectively. All of the studies reported a loss to follow-up data, where 20% (2) was greater than the overall FI of 5. CONCLUSION: The orbital fracture literature provides treatment guidance by relying on statistical significant results from RCTs. However, the RCTs in the orbital fracture peer-reviewed literature may not be statistically stable as previously thought. The sole reliance of the P value may depict misleading results. Thus, we recommend standardizing the reporting of the P value, FI, and FQ in the orbital fracture literature to aid readers in reliably drawing conclusions based on fragility outcome measures impacting clinical decision-making.