Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase.

There is growing appreciation for neuraminidase (NA) as an influenza vaccine target; however, its antigenicity remains poorly characterized. In this study, we isolated three broadly reactive N2 antibodies from the plasmablasts of a single vaccinee, including one that cross-reacts with NAs from seasonal H3N2 strains spanning five decades. Although these three antibodies have diverse germline usages, they recognize similar epitopes that are distant from the NA active site and instead involve the highly conserved underside of NA head domain. We also showed that all three antibodies confer prophylactic and therapeutic protection in vivo, due to both Fc effector functions and NA inhibition through steric hindrance. Additionally, the contribution of Fc effector functions to protection in vivo inversely correlates with viral growth inhibition activity in vitro. Overall, our findings advance the understanding of NA antibody response and provide important insights into the development of a broadly protective influenza vaccine.

Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike.

Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be nonneutralizing, we show that they confer protection in vivo through Fc-mediated effector functions. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.

Egg-adaptive mutations of human influenza H3N2 virus are contingent on natural evolution.

Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptive mutation in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the preference of egg-adaptive mutation. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the preference of egg-adaptation mutation, which has important implications in seed strain selection for egg-based influenza vaccine.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.

BACKGROUND: Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. METHODS: A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). RESULTS: Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. CONCLUSIONS: LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. HIGHTLIGHTS: What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.

Neonatal intracranial haemorrhage secondary to vein of Galen aneurysmal dilatation.

Paediatric neurovascular anomalies associated with the vein of Galen (VG) comprise of a spectrum of rare, complex, and life-threatening conditions. In this group, the "vein of Galen aneurysmal dilatation" (VGAD) is a distinct entity that often presents with progressive neurological symptoms in older children. Acute haemorrhage in VGAD is uncommon. We present an unusual presentation of VGAD in a neonate and discuss the challenges faced in the management.

Optimal reimplantation timing in two-stage exchange for periprosthetic joint infection: an observative cohort study in Asian population.

BACKGROUND: The optimal timing for reimplantation for periprosthetic joint infection (PJI) has not been established and varies from a few weeks to several months. The aim of this study was to assess the commendable time between implant removal and reimplantation in patients who underwent two-stage exchange arthroplasty for PJI. METHODS: We retrospectively reviewed 361 patients who were treated with two-stage exchange arthroplasty for hip and knee chronic PJI at our institution between January 2000 and December 2018. Patient characteristics, comorbidities, surgical variables, microbiology data, and time to reimplantation were recorded. All patients were followed for a minimum of one year. Treatment failure was defined by Delphi criteria. Logistic regression analyses were used to calculate survival rates and adjusted odds ratios (ORs) of treatment failure. RESULTS: In final analysis, 27 (7.5%) had treatment failure. Factors related to treatment failure including interim spacer exchange (OR, 3.13; confidence interval (CI), 1.04-9.09, p = 0.036), higher ESR level at reimplantation (OR, 1.85; CI, 1.05-3.57; p = 0.04), and time to reimplantation (OR, 1.00; CI, 1.003-1.005, p = 0.04). Performing revision arthroplasty surgery from 16 to 20 weeks had highest successful rate. The reimplantation over 24 weeks had a lower successful rate. However, no statistical significance in comparing each interval group. CONCLUSION: Our study emphasized the importance of timely reimplantation in achieving successful outcomes. Factors such as ESR levels, spacer exchange, and the duration of time to reimplantation influenced the likelihood of treatment failure in two-stage exchange arthroplasty for hip and knee PJI.

Ultrasound diagnosis of Mondor's disease involving the superficial scrotal veins: Unveiling a rare mimicker of acute scrotal emergencies.

We describe a rare case of Mondor disease of the superficial scrotal veins, which can clinically mimic acute testicular pathologies such as testicular torsion or epididymo-orchitis, and highlight the value of grayscale/Doppler ultrasound examination in distinguishing these entities, which have different management implications.

Environmental sustainability of post-orthodontic dental retainers: a comparative life-cycle assessment of Hawley and Essix retainers.

BACKGROUND: Environmental sustainability has been brought into the limelight due to the global climate crisis. This crisis is driven by human activities and even the healthcare sector is no exception. Within dentistry, orthodontics is a large global market; hence, the use of post-orthodontic retainers has a significant environmental footprint. The aim of this study was to determine the environmental sustainability of post-orthodontic retention using Hawley and Essix retainers. MATERIALS AND METHODS: A comparative life-cycle assessment (LCA) was carried out to compare the environmental impact of both retainers. All inputs and outputs were accounted for using the Ecoinvent database, v3.7.1, and openLCA software. Sixteen impact categories were used to determine their environmental burden. RESULTS: Of the 16 impact categories, the Hawley had a greater environmental burden than the Essix retainer in 12 categories. The Hawley's most significant contributors to its impact values are factory manufacturing and in-house production, with an average of 41.45% and 52.52%, respectively. For the Essix, the greatest contributor is factory manufacturing, with an average of 64.63%. However, when factoring in the lifespan of the retainers, the Essix would have a greater environmental impact than the Hawley retainer. LIMITATIONS: This study employed a comparative LCA. There were also assumptions made, but these were supported by research. CONCLUSIONS: On the basis of the evidence gathered in this study, Hawley retainers are more environmentally sustainable than Essix retainers. These results would better enable clinicians to factor in the environmental impact and make informed decisions on the choice of retainer type.

Interactions between Influenza A Virus Nucleoprotein and Gene Segment Untranslated Regions Facilitate Selective Modulation of Viral Gene Expression.

The influenza A virus (IAV) genome is divided into eight negative-sense, single-stranded RNA segments. Each segment exhibits a unique level and temporal pattern of expression; however, the exact mechanisms underlying the patterns of individual gene segment expression are poorly understood. We previously demonstrated that a single substitution in the viral nucleoprotein (NP:F346S) selectively modulates neuraminidase (NA) gene segment expression while leaving other segments largely unaffected. Given what is currently known about NP function, there is no obvious explanation for how changes in NP can selectively modulate the replication of individual gene segments. In this study, we found that the specificity of this effect for the NA segment is virus strain specific and depends on the untranslated region (UTR) sequences of the NA segment. While the NP:F346S substitution did not significantly alter the RNA binding or oligomerization activities of NP in vitro, it specifically decreased the ability of NP to promote NA segment viral RNA (vRNA) synthesis. In addition to NP residue F346, we identified two other adjacent aromatic residues in NP (Y385 and F479) capable of similarly regulating NA gene segment expression, suggesting a larger role for this domain in gene-segment specific regulation. Our findings reveal a novel role for NP in selective regulation of viral gene segment replication and provide a framework for understanding how the expression patterns of individual viral gene segments can be modulated during adaptation to new host environments. IMPORTANCE Influenza A virus (IAV) is a respiratory pathogen that remains a significant source of morbidity and mortality. Escape from host immunity or emergence into new host species often requires mutations that modulate the functional activities of the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), which are responsible for virus attachment to and release from host cells, respectively. Maintaining the functional balance between the activities of HA and NA is required for fitness across multiple host systems. Thus, selective modulation of viral gene expression patterns may be a key determinant of viral immune escape and cross-species transmission potential. We identified a novel mechanism by which the viral nucleoprotein (NP) gene can selectively modulate NA segment replication and gene expression through interactions with the segment UTRs. Our work highlights an unexpected role for NP in selective regulation of expression from the individual IAV gene segments.

Prediction of MYCN Gene Amplification in Pediatric Neuroblastomas: Development of a Deep Learning-Based Tool for Automatic Tumor Segmentation and Comparative Analysis of Computed Tomography-Based Radiomics Features Harmonization.

OBJECTIVE: MYCN oncogene amplification is closely linked to high-grade neuroblastoma with poor prognosis. Accurate quantification is essential for risk assessment, which guides clinical decision making and disease management. This study proposes an end-to-end deep-learning framework for automatic tumor segmentation of pediatric neuroblastomas and radiomics features-based classification of MYCN gene amplification. METHODS: Data from pretreatment contrast-enhanced computed tomography scans and MYCN status from 47 cases of pediatric neuroblastomas treated at a tertiary children's hospital from 2009 to 2020 were reviewed. Automated tumor segmentation and grading pipeline includes (1) a modified U-Net for tumor segmentation; (2) extraction of radiomic textural features; (3) feature-based ComBat harmonization for removal of variabilities across scanners; (4) feature selection using 2 approaches, namely, ( a ) an ensemble approach and ( b ) stepwise forward-and-backward selection method using logistic regression classifier; and (5) radiomics features-based classification of MYCN gene amplification using machine learning classifiers. RESULTS: Median train/test Dice score for modified U-Net was 0.728/0.680. The top 3 features from the ensemble approach were neighborhood gray-tone difference matrix (NGTDM) busyness, NGTDM strength, and gray-level run-length matrix (GLRLM) low gray-level run emphasis, whereas those from the stepwise approach were GLRLM low gray-level run emphasis, GLRLM high gray-level run emphasis, and NGTDM coarseness. The top-performing tumor classification algorithm achieved a weighted F1 score of 97%, an area under the receiver operating characteristic curve of 96.9%, an accuracy of 96.97%, and a negative predictive value of 100%. Harmonization-based tumor classification improved the accuracy by 2% to 3% for all classifiers. CONCLUSION: The proposed end-to-end framework achieved high accuracy for MYCN gene amplification status classification.

The impact of COVID-19 and COVID vaccination on cardiovascular outcomes.

COVID-19 is an independent risk factor for cardiovascular disease. COVID-19 vaccination may prevent this, but in some cases, COVID-19 vaccination may cause myocarditis or pericarditis. Patients with COVID-19 may present with non-specific symptoms that have a cardiac origin. This review examines the cardiovascular complications of COVID-19 infection and the impact of COVID-19 vaccination. COVID-19 cardiovascular complications include myocardial injury, pericarditis, coagulopathy, myocardial infarction, heart failure, arrhythmias, and persistent post-acute risk of adverse cardiovascular outcomes. Diagnostic and referral pathways for non-specific symptoms, such as dyspnoea and fatigue, remain unclear. COVID-19 vaccination is cardioprotective overall but is associated with myopericarditis in young males, though at a lower rate than following SARS-CoV-2 infection. Increased awareness among primary care physicians of potential cardiovascular causes of non-specific post-COVID-19 symptoms, including in younger adults, such as fatigue, dyspnoea, and chest pain, is essential. We recommend full vaccination with scheduled booster doses, optimal management of cardiovascular risk factors, rapid treatment of COVID-19, and clear diagnostic, referral, and management pathways for patients presenting with non-specific symptoms to rule out cardiac complications.

Incidence of immune checkpoint inhibitor mediated cardiovascular toxicity: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) are a novel class of anti-cancer therapy becoming increasingly associated with fatal cardiovascular toxicities (CVTs). The aim is to determine the incidence of CVTs in cohorts treated with ICIs as sole anti-cancer therapy. METHODS: A systematic literature search of scientific and medical databases was performed using PRISMA principles to identify relevant cohorts (PROSPERO registration CRD42021272470). Data for specific CVTs (pericardial disease, myocarditis, heart failure, arrhythmia, myocardial infarction/ischaemia and angina), CVT-related death and CV risk factors were extracted. Presence of CVTs in ICI-monotherapy versus combination-ICI therapy, and programmed death 1/programmed death ligand 1- (PD1/PDL1-) versus cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) inhibitor groups were dichotomised and meta-analysed using random-effect models. RESULTS: Forty-eight studies (11,207 patients) were identified, from which 146 CVTs were observed (incidence 1.30%). ICI-monotherapy led to more CVTs than combination therapy (119/9009; 1.32% vs. 18/2086; 0.86%). Across monotherapies, PD1/PDL1-inhibitors had lower incidence of CVTs compared to CTLA4-inhibitors (62/6950; 0.89% vs. 57/2059; 2.77%). Based on eight studies that were meta-analysed, no significant difference was observed comparing monotherapy versus combination-ICI therapy (RR-0.69, 95% CI -1.47 to 0.09) for all CVTs, or PD1/PDL1- to CTLA4-inhibitors (RR-0.27, 95% CI -2.06 to 1.53), for all CVTs including CVT-death. CV risk factors could not be attributed to an ICI group as data was population based rather than individual based. CONCLUSION: ICI-mediated CVTs are rare and potentially fatal. The role of CV risk factors in their development remains unclear.

Prognostic implications of traditional and non-traditional cardiovascular risk factor profiles in patients with non-valvular atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a prevalent disease with associated mortality risk, mediated in large part through its associated cardiovascular risk factors. Standard modifiable cardiovascular risk factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) are established drivers of cardiovascular disease; however, the importance of non-traditional mediators of cardiovascular risk (NTRFs) such as chronic renal impairment, obstructive sleep apnoea and obesity is emerging. The differential impact of these risk factors on outcomes in patients with AF is not well studied. METHODS: Consecutive patients admitted to our service between January 2013 and January 2018 with a primary diagnosis of non-valvular AF were assessed. Assessment of demographic, anthropometric, risk factor profile and pharmacotherapeutics was performed. The clinical course of these patients was followed for up to five years for the composite outcome of all-cause death and major adverse cardiovascular events. RESULTS: Of the 1010 patients (62.29 ± 16.81 years, 51% men) included, 154 (15%) had no risk factors, 478 (47%) had only SMuRFs, 59 (6%) had only NTRFs and 319 (32%) had both SMuRFs and NTRFs. Over a mean follow-up period of 33.18 ± 21.27 months, a total of 288 patients met the composite outcome. On Cox regression, the coexistence of SMuRFs and NTRFs was an independent predictor of the composite outcome (HR 1.40; 95%CI 1.09-1.82, p = .01). Other independent predictors included age, heart failure, CHA2 DS2 VASc score, persistent AF and anaemia. CONCLUSIONS: The presence of both SMuRFs and NTRFs has prognostic implications in patients with non-valvular AF.

Pulmonary artery pressure response to percutaneous mitral valvuloplasty: Associated factors and clinical implications.

BACKGROUND: Pulmonary hypertension (PH) is a marker of poor outcome in mitral stenosis (MS), which improves after percutaneous mitral valvuloplasty (PMV). However, mechanical interventions for relief of valve obstruction often but not always reduce pulmonary pressures. This study aimed to assess the parameters associated with abnormal pulmonary artery pressure (PAP) response immediately after a successful PMV, and also its impact on long-term outcome. METHODS: A total of 181 patients undergoing PMV for rheumatic MS were prospectively enrolled. Invasive hemodynamic and echocardiographic measures were examined in all patients. Abnormal PAP response was defined as the mean PAP (mPAP) values unchanged at the end of the procedure. Long-term outcome was a composite endpoint of death, mitral valve replacement, repeat PMV, new onset of atrial fibrillation (AF), or stroke. RESULTS: The mean age was 44.1 ± 12.6 years, and 157 patients were women (86.7%). In the overall population, mPAP decreased from 33.4 ± 13.1 mmHg pre to 27.6 ± 9.8 mmHg post (p < 0.001). Following PMV, 52 patients (28.7%) did not have any reduction of mPAP immediately after the PMV. Multivariable analysis adjusting for baseline values of PAP and mitral valve area revealed that AF (Odds ratio [OR] 2.7, 95% [confidence interval] CI 1.3 to 6.7), maximum mitral valve leaflets displacement (OR 0.8, 95% CI 0.7 to 0.9), and post-procedural left ventricular compliance (OR 0.7, 95% CI 0.5 to 0.9) were predictors of a lack of improvement in mPAP. During a median follow-up of 4.4 years, the endpoint was reached in 56 patients (31%). The pulmonary pressure response to PMV was not an independent predictor of long-term events. CONCLUSIONS: In patients with MS undergoing PMV, pulmonary pressures may not reduce immediately after the procedure, despite adequate opening of the valve. Abnormal PAP response can be predicted from baseline clinical and valvular characteristics as well as post-procedural left ventricular compliance. The lack of any immediate reduction in mPAP is not associated with long-term adverse outcomes.

A systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulants vs vitamin K antagonists after transcatheter aortic valve replacement in patients with atrial fibrillation.

PURPOSE: Transcatheter aortic valve replacement (TAVR) is increasingly carried out in patients with aortic valvular conditions. Atrial fibrillation (AF) is a common comorbidity among patients undergoing TAVR. Despite this, there remains a paucity of data and established guidelines regarding anticoagulation use post-TAVR in patients with AF. METHODS: Four databases were searched from inception until 12 October 2021. A title and abstract sieve, full-text review and data extraction were conducted by independent authors, and articles including patients without AF were excluded. The Review Manager (Version 5.4) was utilised in data analysis. RESULTS: A total of 25,199 post-TAVR patients with AF were included from seven articles, with 9764 patients on non-vitamin K antagonist oral anticoagulants (NOAC) and 15,435 patients on vitamin K antagonists (VKA). In this analysis, there was a significantly lower risk of all-cause mortality at 1 year (RR: 0.75, CI: 0.58-0.97, p = 0.04, I2 = 56%), and bleeding at 1 year (RR: 0.73, CI: 0.68-0.79, p = < 0.00001, I2 = 0%), between patients on NOAC and VKA. There were no detectable differences between patients on NOAC and VKA for all-cause mortality at 2 years, stroke within 30 days, stroke within 1 year, ischaemic stroke at 1 year and life-threatening bleeding at 30 days. CONCLUSION: While the results of this analysis reveal NOAC as a potential alternate treatment modality to VKA in post-TAVR patients with AF, further research is needed to determine the full safety and efficacy profile of NOAC (PROSPERO: CRD42021283548).

Interim Spacer Exchange for Treatment of Periprosthetic Joint Infection: Almost Half the Patients Subsequently Fail.

BACKGROUND: Interim spacer exchange may be performed in patients undergoing 2-stage exchange for periprosthetic joint infection. Several studies have demonstrated that interim spacer exchange is associated with poor outcomes. This study investigated the survivorship and risk factors for failure in patients with an interim spacer exchange. METHODS: Two institutional databases identified 182 patients who underwent spacer exchange from 2000 to 2017. Primary outcomes included progression to reimplantation, treatment success, and mortality. Bivariate analysis was performed to evaluate risk factors associated with failure. Kaplan-Meier curves using host and local grades were generated to evaluate for primary outcomes and differences in survivorship. RESULTS: The overall failure rate was 49% in patients with a spacer exchange. Most patients (60%) failed before 2 years. Higher comorbidity scores, elevated erythrocyte sedimentation rate, and non-White race were more prevalent in patients who failed. Negative cultures at the time of exchange were more prevalent in patients who did not fail. Failure rate was higher in immunocompromised conditions, and those who had revision prior to exchange. After considering clinically relevant variables, advanced host grade C was the single factor associated with treatment failure. Although survivorship curves were not significantly different between extremity local grades, higher host grades were associated with treatment failure. CONCLUSION: Almost 1 out of 2 patients with spacer exchange were found to fail the intended 2-stage revision arthroplasty. Benefits of delivering additional antibiotic load with a new spacer should be balanced against poor outcomes in patients with the aforementioned risk factors.

Worse Outcomes Are Associated With Proximal Femoral Replacement Following Periprosthetic Joint Infection.

BACKGROUND: Proximal femoral replacements (PFRs) are often used in the setting of severe bone loss. As osteolysis has become less common, PFR may be used to address other causes of bone loss such as infection or periprosthetic fracture. The aim of this study is to investigate the clinical outcomes of PFR for non-neoplastic conditions. METHODS: A retrospective review of 46 patients undergoing PFR at a single institution was performed. The electronic records were reviewed to extract relevant information including the reason for use of PFR, surgical variables, follow-up, and complications. Survivorship curves were generated and differences in survivorship were evaluated using the log-rank test. Radiographic evaluation was also performed. RESULTS: Using revision as an endpoint, the Kaplan-Meier analysis of the entire cohort demonstrated a survival rate of 74% at 1 year and 67% at 5 years. Patients with a preoperative diagnosis of periprosthetic joint infection demonstrated the lowest survivorship with a failure rate of 47%. Furthermore, a high dislocation rate at 17.4% (n = 8) was observed. The use of dual-mobility articulation was effective in reducing dislocation. CONCLUSION: PFR is a valuable reconstructive option for patients with massive proximal femoral bone loss. This study demonstrates that patients with periprosthetic joint infection who undergo PFR reconstruction are at very high risk of subsequent failure, most commonly from reinfection and instability. The use of a dual-mobility articulation in association with PFR appears to help mitigate risk of subsequent dislocation.

Which Minor Criteria is the Most Accurate Predictor for the Diagnosis of Hip and Knee Periprosthetic Joint Infection in the Asian Population?

BACKGROUND: The aim of this study was to evaluate the diagnostic performance of minor criteria from the 2018 International Consensus Meeting (ICM) for the diagnosis of chronic periprosthetic joint infection (PJI) in an Asian population. METHODS: We retrospectively reviewed 76 patients who underwent a revision knee or hip arthroplasty at an academic institution between September 2018 and December 2019. All major and minor 2018 ICM criteria were available for all patients included. Cases with at least 1 major criterion or score ≥6 in minor criteria were considered as infected. The diagnostic performance was evaluated by a receiver operative characteristic curve analysis and area under the curve (AUC) for each minor criterion. An AUC value of more than 0.9 was considered outstanding and 0.8-0.9 as excellent. RESULTS: When using 2018 ICM threshold, the diagnostic performance ranked based on AUC was the following: alpha defensin (0.92), positive histology (0.83), leukocyte esterase (0.82), synovial white blood cell (0.81), serum erythrocyte sedimentation rate (0.78), synovial polymorphonuclear neutrophils (0.77), serum C-reactive protein (0.74), D-dimer (0.59), single positive culture (0.53), and positive intraoperative purulence (0.51). Alpha defensin was considered as an outstanding test among the 2018 ICM minor criteria. Positive histology, leukocyte esterase, and synovial white blood cell were considered as excellent tests. CONCLUSION: Based on our findings, alpha-defensin has the best diagnostic performance in Asian population among the minor criteria of 2018 ICM.

Embolic Stroke of Undetermined Source: Approaches in Risk Stratification for Cardioembolism.

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Embolic stroke of undetermined source has been recently proposed to categorize nonlacunar ischemic strokes without confirmed etiology after adequate investigation with a likely embolic stroke mechanism. A strategy of empirical anticoagulation for embolic stroke of undetermined source patients is attractive but may only be beneficial in a select subset of patients. Strategies which would help identify the subset of embolic stroke of undetermined source patients most likely to have cardioembolic origin of stroke, and hence benefit from anticoagulation, are needed. This article will review current evidence which may be useful in the development of a risk stratification approach based on arrhythmia monitoring, cardiac imaging, and clinical risk stratification. This approach may be beneficial in clinical practice in improving patient outcomes and reducing stroke recurrence in this population; however, further work is required with active trials underway.