Cementless Total Knee Arthroplasty: A State-of-the-Art Review.

¼ The demographic profile of candidates for total knee arthroplasty (TKA) is shifting toward younger and more active individuals.¼ While cemented fixation remains the gold standard in TKA, the interest is growing in exploring cementless fixation as a potentially more durable alternative.¼ Advances in manufacturing technologies are enhancing the prospects for superior long-term biological fixation.¼ Current research indicates that intermediate to long-term outcomes of modern cementless TKA designs are comparable with traditional cemented designs.¼ The selection of appropriate patients is critical to the success of cementless fixation techniques in TKA.¼ There is a need for high-quality research to better understand the potential differences and relative benefits of cemented vs. cementless TKA systems.

Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

Single versus double percutaneous pinning of pediatric distal radius fractures.

The aim of this study was to compare early clinical and radiographic results of single- versus double-pin fixation of unstable pediatric distal radius fractures. A total of 103 consecutive closed distal radius fractures treated with either single or double percutaneous pinning at a tertiary level I pediatric hospital were analyzed. All patients had open physes and had fractures that failed initial closed reduction and casting. Postoperative fracture displacement was assessed by measuring the difference in angulation of the radius in the anteroposterior and lateral views from intraoperative fluoroscopic images to postoperative radiographs taken on the day of pin removal. Complications were identified from the medical record review. In 103 operative distal radius fractures in 101 patients (70 males, 31 females), 52 and 51 distal radius fractures were treated with single and double pinning, respectively. The median [interquartile range (IQR)] age at the time of surgery was 12.1 (9.0-14.0) years, with the single-pinning group being younger by 1.9 years (P < 0.01). Median (IQR) postoperative angulation in the anteroposterior radiograph (coronal plane) was 2° (1-7°) with one pin versus 1° (0-2°) with two pins (P < 0.01). Median (IQR) postoperative angulation in the lateral radiograph (sagittal plane) was 3° (1-10°) with one pin versus 1° (0-2°) with two pins (P < 0.01). There were no significant differences in complications between the single- and double-pinning groups. Double-pin fixation resulted in a statistically significant, but clinically negligible, reduction in postoperative fracture displacement compared with single-pin fixation. Complication rates were similar in both groups. These findings suggest that either single- or double-pinning techniques can be effective, provided appropriate reduction and postoperative immobilization are achieved.

The Association of Oxygen Delivery and Transfusion on Cardiopulmonary Bypass with Acute Kidney Injury.

OBJECTIVES: To estimate whether the association of transfusion and acute kidney injury (AKI) has a threshold of oxygen delivery below which transfusion is beneficial but above which it is harmful. DESIGN: Retrospective study SETTING: Cardiovascular operating room and intensive care unit PARTICIPANTS: Patients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to estimate the associations between oxygen delivery (mean, cumulative deficit, and bands of oxygen delivery), transfusion, and their interaction and AKI. A subgroup analysis of transfused and nontransfused patients with exact matching on cumulative oxygen deficit and time on bypass with adjustment for propensity to receive a transfusion using logistic regression. Nine hundred ninety-one of 4,203 patients developed AKI within 7 days. After adjustment for confounders, lower mean oxygen delivery (odds ratio [OR], 0.968; 95% confidence interval [CI], 0.949-0.988; p = 0.002) and transfusions (OR, 1.442; 95% CI, 1.077, 1.932; p = 0.014) were associated with increased odds of AKI by 7 days. As oxygen delivery decreased, the risk of AKI increased, with the slope of the OR steeper at <160 mL/m2/min. In the subgroup analysis, matched transfused patients were more likely than matched nontransfused patients to develop AKI (45% [n = 145] v 31% [n = 101]; p < 0.001). However, after propensity score adjustment, the difference was nonsignificant (OR, 1.181; 95% CI, 0.796-1.752; p = 0.406). CONCLUSIONS: We found a nonlinear relationship between oxygen delivery and AKI. We found no level of oxygen delivery at which transfusion was associated with a decreased risk of AKI.

Assessment of the Behaviors of an In Vitro Brain Model On-Chip under Shockwave Impacts.

Herein we report the assessment of the effects of shockwave (SW) impacts on adult rat hippocampal progenitor cell (AHPC) neurospheres (NSs), which are used as in vitro brain models, for enhancing our understanding of the mechanisms of traumatic brain injury (TBI). The assessment has been achieved by using culture dishes and a new microchip. The microchip allows the chemicals released from the brain models cultured inside the cell culture chamber under SW impacts to diffuse to the nanosensors in adjacent sensor chambers through built-in diffusion barriers, which are used to prevent the cells from entering the sensor chambers, thereby mitigating the biofouling issues of the sensor surface. Experiments showed the negative impact of the SW on the viability, proliferation, and differentiation of the cells within the NSs. A qPCR gene expression analysis was performed and appeared to confirm some of the immunocytochemistry (ICC) results. Finally, we demonstrated that the microchip can be used to monitor lactate dehydrogenase (LDH) released from the AHPC-NSs subjected to SW impacts. As expected, LDH levels changed when AHPC-NSs were injured by SW impacts, verifying this chip can be used for assessing the degrees of injuries to AHPC-NSs by monitoring LDH levels. Taken together, these results suggest the feasibility of using the chip to better understand the interactions between SW impacts and in vitro brain models, paving the way for potentially establishing in vitro TBI models on a chip.

Pediatric and Adolescent Distal Radius Fractures: Current Concepts and Treatment Recommendations.

Distal radius fractures are the most common skeletal injuries requiring intervention in children. These injuries are classified by fracture pattern, location, displacement, and angulation. While each unique fracture pattern warrants slightly modified treatment plans and follow-up, the goals of treatment remain constant. Successful outcomes depend on restoration of motion and function, and attaining acceptable sagittal and coronal alignment is a necessary first step. For displaced fractures, closed reduction is often necessary to restore alignment; well-molded cast application is important to maintain fracture alignment. Fractures with bayonet apposition, if well aligned, may not need formal reduction in some patients. Special attention should be paid to the physis-not only for physeal-involving fractures but also for all distal radius fractures-given that the proximity to the physis and amount of remaining skeletal growth help guide treatment decisions. Casting technique is essential in optimizing the best chance in maintaining fracture reduction. Surgical intervention may be indicated for a subset of fractures when acceptable alignment is not achieved or is lost at subsequent follow-up. Even among experts in the field, there is little consensus as to the optimal treatment of displaced metaphyseal fractures, illustrating the need for prospective, randomized studies to establish best practices.

Risk factors for failure of manipulation under anesthesia after total knee arthroplasty.

BACKGROUND: Manipulation under anesthesia (MUA) is a well-established treatment for stiffness after total knee arthroplasty (TKA). Risk factors for failure of MUA remain largely unknown. The primary aim of this study was to identify risk factors for failure of MUA after TKA. METHODS: We performed a retrospective cohort study including 470 patients who underwent MUA after primary TKA with minimum 2 year follow-up. Patients were grouped into success (n = 412) or failure (n = 58) cohorts; failure was defined as flexion < 90° at most recent follow-up or revision for stiffness. The increase in flexion post-MUA for the cohort was calculated. Several clinical, patient, and surgical factors were analyzed using univariate, followed by multivariable logistic regression models to identify independent risk factors associated with failure. RESULTS: The mean increase in flexion was 42° (range 0-115). BMI 30-35 (p = 0.01, odds ratio (OR) 2.42; 95% CI 1.25-4.68) and poorer pre-MUA flexion (p < 0.01, OR 1.43; 95% CI 1.23-1.67) were risk factors for failure. When considering revision for stiffness only, BMI 30-35 (p = 0.01, OR 3.27; 95% CI 1.41-7.61), lower pre-MUA flexion (p < 0.01, OR 1.43; 95% CI 1.18-1.75), and history of prior knee surgery (p = 0.04, OR 2.31; 95% CI 1.06-5.04) were predictors of failure. Time to MUA (p = 0.48), thromboprophylaxis (p = 0.44), pre-operative opioid use (p = 0.34), depression/anxiety (p = 1.0), and several other factors analyzed were not associated with failure. CONCLUSION: In this large cohort, elevated BMI and lower pre-MUA flexion were risk factors for failure of MUA. History of prior knee surgery was an additional predictor of requiring revision for stiffness.

The John Charnley Award: The Impact of Human Leukocyte Antigen Genotype on Bacterial Infection Rates and Successful Eradication in Total Hip Arthroplasty.

BACKGROUND: Genetics play an important role in several medical domains; however, the influence of human leukocyte antigen (HLA) genotype on the development of periprosthetic joint infection (PJI) in total hip arthroplasty (THA) remains unknown. The primary aim of this study was to determine if HLA genotype is associated with the development of bacterial PJI in THA. Secondarily, we evaluated the association between HLA genotype and PJI treatment success. METHODS: A retrospective, matched, case-control study was performed using prospectively collected data from a single institution. A total of 49 patients who underwent primary THA were included, with a mean follow-up of 8.5 years (range, 4.2 to 12.9). The 23 cases (PJI) and 26 controls (no PJI) were matched for age, sex, follow-up, body mass index, primary diagnosis, and comorbidities (P > .05). High-resolution genetic analysis targeting 11 separate HLA loci was performed in all patients using serum samples. The HLA gene frequencies and carriage rates were determined and compared between cohorts. A subgroup analysis of PJI treatment success (18) and failure (5) was performed. Statistical significance was set at P = .10 for genetic analysis and at 0.05 for all other analyses. RESULTS: There were 4 HLA alleles that were significantly associated with the development of PJI. The 3 at-risk alleles included HLA-C∗06:02 (odds ratio 5.25, 95% CI [confidence interval] 0.96 to 28.6, P = .064), HLA-DQA1∗04:01 (P = .096), and HLA-DQB1∗04:02 (P = .096). The single protective allele was HLA-C∗03:04 (odds ratio 0.12, 95% CI 0.01 to 1.10, P = .052). There were no specific HLA alleles that were associated with treatment success or failure. CONCLUSIONS: This study suggests that there are at-risk and protective HLA alleles associated with the development of PJI in THA. To our knowledge, this is the first study to demonstrate an association between patient HLA genotype and the development of PJI. A larger study of the subject matter is necessary and warranted.

Perfusion Measures and Outcomes (PERForm) registry: First annual report.

BACKGROUND: The Perfusion Measures and Outcomes (PERForm) registry was established in 2010 to advance cardiopulmonary bypass (CPB) practices and outcomes. The registry is maintained through the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative and is the official registry of the American Society of Extracorporeal Technology. METHODS: This first annual PERForm registry report summarizes patient characteristics as well as CPB-related practice patterns in adult (≥18 years of age) patients between 2019 and 2022 from 42 participating hospitals. Data from PERForm are probabilistically matched to institutional surgical registry data. Trends in myocardial protection, glucose, anticoagulation, temperature, anemia (hematocrit), and fluid management are summarized. Additionally, trends in equipment (hardware/disposables) utilization and employed patient safety practices are reported. RESULTS: A total of 40,777 adult patients undergoing CPB were matched to institutional surgical registry data from 42 hospitals. Among these patients, 54.9% underwent a CABG procedure, 71.6% were male, and the median (IQR) age was 66.0 [58.0, 73.0] years. Overall, 33.1% of the CPB procedures utilized a roller pump for the arterial pump device, and a perfusion checklist was employed 99.6% of the time. The use of conventional ultrafiltration decreased over the study period (2019 vs. 2022; 27.1% vs. 24.9%) while the median (IQR) last hematocrit on CPB has remained stable [27.0 (24.0, 30.0) vs. 27.0 (24.0, 30.0)]. Pump sucker termination before protamine administration increased over the study period: (54.8% vs. 75.9%). CONCLUSION: Few robust clinical registries exist to collect data regarding the practice of CPB. Although data submitted to the PERForm registry demonstrate overall compliance with published perfusion evidence-based guidelines, noted opportunities to advance patient safety and outcomes remain.

Nonoperative Versus Operative Treatment of Z-Type Comminuted Clavicle Fractures in Adolescents: A Prospective Substratified Cohort Analysis.

OBJECTIVES: To compare the clinical, radiographic, and patient-reported outcomes of nonoperative and operative treatment of adolescents with comminuted "Z-type" midshaft clavicle fractures. DESIGN: Prospective observational cohort. SETTING: Eight tertiary care pediatric centers. PATIENT SELECTION CRITERIA: Patients aged 10-18 years who were treated either operatively or nonoperatively for a diaphyseal clavicle fracture between 2013 and 2017 were screened/enrolled at the time of injury. The current subcohort analysis was derived from a larger adolescent clavicle study population of 907 patients. OUTCOME MEASUREMENTS AND COMPARISONS: Complications and validated patient-reported outcome measures (PROs):(ASES, QuickDASH, Marx Shoulder Activity Score, EQ-5D, EQ-VAS, and patient satisfaction score) were compared between operative and nonoperative cohorts. RESULTS: Eighty-one patients (69 male [85.2%], 12 female; average age 15 years [11.1-18.7]; 78 with sports participation [96.2%]) were followed through bony healing and return to sports, while 59 patients (73%) completed 2-year follow-up with PROs, 26 of whom were treated nonoperatively and 33 treated operatively. All demographic and fracture characteristics were similar (P > 0.05) between the 2-year follow-up cohorts except for fracture shortening, which was greater in the operative cohort (23 vs. 29 mm, P = 0.01). After controlling for this potential confounder through both regression and propensity matched subgroup analysis, nonoperative versus operative cohorts showed no difference in rates of nonunion (0%), delayed union (0% vs. 2.3%, P = 1.0), symptomatic malunion (2.7% vs. 0%, P = 0.4), refracture (2.7% vs. 2.2%, P = 1.0), unexpected subsequent surgery (5.4% vs. 11.4%, P = 0.45), or clinically significant complications (5.4% vs. 16%, P = 0.17). There were no differences in any PROs between cohorts, both before and after controlling for the difference in fracture shortening (all P-values >0.05). CONCLUSIONS: In this prospective comparison of complications and 2-year PROs in adolescents with comminuted Z-type clavicle fractures, nonoperative and operative treatment yielded similar outcomes. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study.

BACKGROUND: Garadacimab is a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII. This study evaluated long-term efficacy, health-related quality of life (HRQoL), and safety data for garadacimab in adults with hereditary angioedema. METHODS: This global phase 2 study comprised a treatment period 1 (TP1: 12 weeks, double-blind, placebo-controlled) and a treatment period 2 (TP2: ≥44-week open-label extension). Patients aged 18-65 years with clinically confirmed hereditary angioedema were eligible. In TP1, 32 patients were randomly assigned (1:1:1:1) to receive subcutaneous garadacimab (75 mg, 200 mg, or 600 mg) or placebo every 4 weeks (once monthly). Randomisation was done using interactive response technology via block randomisation (block sizes 1-4). Subsequently, six additional patients in TP1 were assigned to open-label garadacimab 400 mg every 2 weeks. At the start of TP2, patients were re-randomised (if receiving placebo, garadacimab 75 mg, or garadacimab 400 mg) or continued to receive garadacimab 200 mg or garadacimab 600 mg once monthly. After a protocol amendment on March 20, 2020, patients originally assigned to the 600 mg dose were down-titrated to 200 mg at their next visit. The primary endpoint (published previously) was monthly attack rate for patients receiving 200 mg or 600 mg garadacimab in TP1 in the intention-to-treat population. Here, we assessed the impact of garadacimab on patient-reported and investigator-reported outcomes and HRQoL as well as long-term efficacy and safety. This trial is registered with ClinicalTrials.gov, NCT03712228, and is completed. FINDINGS: Of 54 patients screened between Oct 29, 2018, and Aug 28, 2019, 32 randomised and six open-label patients completed TP1 and entered TP2 (20 in the garadacimab 200 mg group; 18 in the garadacimab 600 mg group; total 38 patients). Median age was 39·0 years (IQR 27·0-53·0), and 21 patients (55%) were female and 17 (45%) were male. In TP2, the median garadacimab exposure was 87·9 weeks (IQR 50·0-106·6) in the garadacimab 200 mg group and 44·1 weeks (24·1-56·1) in the garadacimab 600 mg group. Median monthly attack rates were 0·0 (IQR 0·0-0·1) in the garadacimab 200 mg group and 0·1 (0·0-0·4) in the garadacimb 600 mg group. Median reduction in monthly attack rate versus run-in was 100% (IQR 98-100) with garadacimab 200 mg. HRQoL improvements observed during TP1 with garadacimab were sustained throughout TP2. TP2 safety signals were consistent with TP1. Two patients experienced serious adverse events of diverticular perforation and asthma (not garadacimab-related). Treatment-emergent adverse events were mostly mild or moderate in severity. The most common adverse events were headache (nine of 38, 24%) and abdominal pain (seven of 38, 18%). There were no treatment-related deaths. INTERPRETATION: Once-monthly garadacimab for more than 2 years in patients with hereditary angioedema was well tolerated and efficacious in reducing monthly attack rate and improving HRQoL. These results reveal the potential of long-term prophylactic treatment with 200 mg once-monthly garadacimab towards complete disease control of patients with hereditary angioedema. FUNDING: CSL Behring.

Hypnotic treatment improves sleep architecture and EEG disruptions and rescues memory deficits in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS) is associated with disrupted cognition and sleep abnormalities. Sleep loss negatively impacts cognitive function, and one untested possibility is that disrupted cognition in FXS is exacerbated by abnormal sleep. We tested whether ML297, a hypnotic acting on G-protein-activated inward-rectifying potassium (GIRK) channels, could reverse sleep phenotypes and disrupted memory in Fmr1-/y mice. Fmr1-/y mice exhibit reduced non-rapid eye movement (NREM) sleep and fragmented NREM architecture, altered sleep electroencephalogram (EEG) oscillations, and reduced EEG coherence between cortical areas; these are partially reversed following ML297 administration. Treatment following contextual fear or spatial learning restores disrupted memory consolidation in Fmr1-/y mice. During memory recall, Fmr1-/y mice show an altered balance of activity among hippocampal principal neurons vs. parvalbumin-expressing interneurons; this is partially reversed by ML297. Because sleep disruption could impact neurophysiological phenotypes in FXS, augmenting sleep may improve disrupted cognition in this disorder.

The Long Non-Coding RNA Gene AC027288.3 Plays a Role in Human Endometrial Stromal Fibroblast Decidualization.

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine was further characterized. One of these, AC027288.3, showed a dramatic increase in the expression of hESF cells undergoing decidualization. When AC027288.3 expression was targeted, the ability of the cells to undergo decidualization as determined by the expression of decidualization marker protein-coding genes was significantly altered. The most affected markers of decidualization whose expression was significantly reduced were FOXO1, FZD4, and INHBA. Therefore, AC027288.3 may be a major upstream regulator of the WNT-FOXO1 pathway and activin-SMAD3 pathways previously shown as critical for hESF decidualization. Finally, we explored possible regulators of AC027288.3 expression during human ESF decidualization. Expression was regulated by cAMP and progesterone. Our results suggest that AC027288.3 plays a role in hESF decidualization and identifies several other lncRNA genes that may also play a role.

Home Health Care Use and Outcomes After Coronary Artery Bypass Grafting Among Medicare Beneficiaries.

BACKGROUND: Home health care (HHC) has been increasingly used to improve care transitions and avoid poor outcomes, but there is limited data on its use and efficacy following coronary artery bypass grafting. The purpose of this study was to describe HHC use and its association with outcomes among Medicare beneficiaries undergoing coronary artery bypass grafting. METHODS: Retrospective analysis of 100% of Medicare fee-for-service files identified 77 331 beneficiaries undergoing coronary artery bypass grafting and discharged to home between July 2016 and December 2018. The primary exposure of HHC use was defined as the presence of paid HHC claims within 30 days of discharge. Hierarchical logistic regression identified predictors of HHC use and the percentage of variation in HHC use attributed to the hospital. Propensity-matched logistic regression compared mortality, readmissions, emergency department visits, and cardiac rehabilitation enrollment at 30 and 90 days after discharge between HHC users and nonusers. RESULTS: A total of 26 751 (34.6%) of beneficiaries used HHC within 30 days of discharge, which was more common among beneficiaries who were older (72.9 versus 72.5 years), male (79.4% versus 77.4%), White (90.2% versus 89.2%), and not Medicare-Medicaid dual eligible (6.7% versus 8.8%). The median hospital-level rate of HHC use was 31.0% (interquartile range, 13.7%-54.5%) and ranged from 0% to 94.2%. Nearly 30% of the interhospital variation in HHC use was attributed to the discharging hospital (intraclass correlation coefficient, 0.296 [95% CI, 0.275-0.318]). Compared with non-HHC users, those using HHC were less likely to have a readmission or emergency department visit, were more likely to enroll in cardiac rehabilitation, and had modestly higher mortality within 30 or 90 days of discharge. CONCLUSIONS: A third of Medicare beneficiaries undergoing coronary artery bypass grafting used HHC within 30 days of discharge, with wide interhospital variation in use and mixed associations with clinical outcomes and health care utilization.

Evaluation of sex differences in the receipt of concomitant atrial fibrillation procedures during nonmitral cardiac surgery.

OBJECTIVE: Women are less likely to receive guideline-recommended cardiovascular care, but evaluation of sex-based disparities in cardiac surgical procedures is limited. Receipt of concomitant atrial fibrillation (AF) procedures during nonmitral cardiac surgery was compared by sex for patients with preoperative AF. METHODS: Patients with preoperative AF undergoing coronary artery bypass grafting and/or aortic valve replacement at any of the 33 hospitals in Michigan from 2014 to 2022 were included. Patients with prior cardiac surgery, transcatheter AF procedure, or emergency/salvage status were excluded. Hierarchical logistic regression identified predictors of concomitant AF procedures, account for hospital and surgeon as random effects. RESULTS: Of 5460 patients with preoperative AF undergoing nonmitral cardiac surgery, 24% (n = 1291) were women with a mean age of 71 years. Women were more likely to have paroxysmal (vs persistent) AF than men (80% vs 72%; P < .001) and had a higher mean predicted risk of mortality (5% vs 3%; P < .001). The unadjusted rate of concomitant AF procedure was 59% for women and 67% for men (P < .001). After risk adjustment, women had 26% lower adjusted odds of concomitant AF procedure than men (adjusted odds ratio, 0.74; 95% CI, 0.64-0.86; P < .001). Female sex was the risk factor associated with the lowest odds of concomitant AF procedure. CONCLUSIONS: Women are less likely to receive guideline recommended concomitant AF procedure during nonmitral surgery. Identification of barriers to concomitant AF procedure in women may improve treatment of AF.

Ebola Virus-Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort.

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013-2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms-ophthalmologic and auditory-are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody.

Identification and characterization of a nonbiological small-molecular mimic of a Zika virus conformational neutralizing epitope.

Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based bead screening was used to select molecules that bound IgG from ZIKV-immune but not from dengue-immune sera. Deep sequencing of the DNA from the "Zika-only" beads identified 40 candidate molecular structures. A lead candidate small molecule "CZV1-1" was selected that correctly identifies serum specimens from Zika-experienced patients with good sensitivity and specificity (85.3% and 98.4%, respectively). Binding competition studies of purified anti-CZV1-1 IgG against known ZIKV-specific monoclonal antibodies (mAbs) showed that CZV1-1 mimics a nonlinear, neutralizing conformational epitope in the domain III of the ZIKV envelope. Purified anti-CZV1-1 IgG neutralized infection of ZIKV in cell cultures with potencies comparable to highly specific ZIKV-neutralizing mAbs. This study demonstrates an innovative approach for identification of synthetic non-natural molecular mimics of conformational virus epitopes. Such molecular mimics may have value in the development of accurate diagnostic assays for Zika, as well as for other viruses.

Re-evaluation of the methodology for estimating the US specialty physician workforce.

Increasing pursuit of subspecialized training has quietly revolutionized physician training, but the potential impact on physician workforce estimates has not previously been recognized. The Physicians Specialty Data Reports of the Association of American Medical Colleges, derived from specialty designations in the American Medical Association (AMA) Physician Professional Data (PPD), are the reference source for US physician workforce estimates; by 2020, the report for pathologists was an undercount of 39% when compared with the PPD. Most of the difference was due to the omission of pathology subspecialty designations. The rest resulted from reliance on only the first of the AMA PPD's 2 specialty data fields. Placement of specialty designation in these 2 fields is sensitive to sequence of training and is thus affected by multiple or intercalated (between years of residency training) fellowships. Both these phenomena have become progressively more common and are not unique to pathology. Our findings demonstrate the need to update definitions and methodology underlying estimates of the US physician workforce for pathology and suggest a like need in other specialties affected by similar trends.

The Wagner Cone Stem for Atypical Femoral Anatomy in Total Hip Arthroplasty: A Report of 320 Cases with Minimum 5-Year Follow-up.

BACKGROUND: The Wagner Cone Prosthesis was designed to address complex femoral deformities during total hip arthroplasty (THA), but its mid-term component survivorship and functional outcomes remain undetermined. The objectives of this study were to determine the implant survivorship, patient satisfaction, functional outcomes, osseointegration as seen radiographically, implant subsidence, and complications of THA using the Wagner Cone Prosthesis stem at intermediate-term follow-up. METHODS: This study involved 302 patients with proximal femoral deformities, including developmental hip dysplasia and Legg-Calvé-Perthes disease, who underwent a total of 320 primary THAs using the Wagner Cone Prosthesis. The average age at the time of surgery was 49.4 ± 14.5 years (range, 18.8 to 85.6 years). Patient satisfaction was recorded using a self-administered questionnaire assessing satisfaction in 4 domains. The University of California at Los Angeles (UCLA) activity score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Oxford Hip Score (OHS), the Forgotten Joint Score (FJS), radiographic outcomes, and complications were recorded. The mean follow-up time was 10.1 years (range, 5.2 to 15.5 years). RESULTS: Survivorship of the Wagner Cone Prosthesis was 98.7% (95% confidence interval [CI]: 97.2% to 100%) with stem revision as the end point and 95.8% (95% CI: 93.5% to 98.2%) with reoperation for any reason as the end point at 10 years postoperatively. In total, 3 stems were revised: 2 for infection and 1 for chronic hip dislocation. The median patient satisfaction score was 95 (interquartile range [IQR], 80 to 100), median UCLA score was 6 (IQR, 6 to 7), median WOMAC score was 18 (IQR, 16 to 22), median OHS was 40 (IQR, 36 to 47), and median FJS was 80 (IQR, 76 to 88) at the time of final follow-up. All Wagner Cone stems that were not revised showed radiographic evidence of osseointegration, with a mean stem subsidence of 0.9 ± 0.8 mm at the most recent follow-up. CONCLUSIONS: The use of the Wagner Cone Prosthesis stem in patients with complex femoral anatomy undergoing primary THA is associated with excellent component survivorship, high levels of patient satisfaction, good functional outcomes, and reliable osseointegration with minimal stem subsidence as seen on radiographs at intermediate-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.