Matrix metalloproteinase-11 regulates inverted papilloma epithelial cell migration and invasion.

BACKGROUND: Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion. METHODS: Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures. RESULTS: IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion. CONCLUSION: We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.

Perceptions about dementia clinical trials among underrepresented populations: A nationally representative survey of U.S. dementia caregivers.

Background: The research community has historically failed to enroll diverse groups of participants in dementia clinical trials. A unique aspect of dementia care research is the requirement of a study partner, who can attest to the care recipient's clinical and functional capacity. The aim of this study is to assess racial and ethnic differences and the importance of various trial considerations among dementia caregivers, in their decision to participate in clinical research as study partners. Method: We embedded a vignette about a hypothetical dementia clinical trial in a nationally representative survey of U.S. dementia caregivers, oversampling non-Hispanic Black and Hispanic caregivers. Dementia caregivers were asked about their willingness to participate in the trial with their care recipient and rated the importance of nine considerations in hypothetical decisions to participate. Caregiver demographic characteristics were analyzed as predictors of trial participation in a base demographic model. In a second reasons model caregiver demographic characteristics and the rated importance of the nine considerations were separately analyzed as predictors; both models used survey-weighted logistic regression. Result: The sample consisted of 610 dementia caregivers, including 156 non-Hispanic Black and 122 Hispanic caregiver participants. In the base demographic model, hypothetical trial participation was negatively associated with older caregiver age (OR (odds ratio) = 0.72, p = < 0.001). In the reasons model, the rated importance of a social responsibility to help others by participating in research was significantly associated with participation (OR = 1.56, p = 0.049), while the importance of the possibility of the care recipient experiencing serious side effects was negatively associated with participation (OR = 0.51, p = 0.003). In both models there was no significant difference in hypothetical participation between non-Hispanic Black and non-Hispanic White caregivers, or between Hispanic and non-Hispanic White caregivers. Conclusion: Hispanic and non-Hispanic Black dementia caregivers were not less likely than non-Hispanic White dementia caregivers to participate in a hypothetical dementia clinical trial. Our study suggests that failures to recruit diverse populations in dementia clinical research are not attributable to less willingness among members of underrepresented groups but may instead reflect structural barriers and historic exclusion from trial participation.

The influence of exogenous amines on the electrochemical CO2 reduction activity of a cobalt-pyridyldiimine catalyst.

Studying the interactions between CO2 sorbents and electrocatalysts for the electrochemical CO2 reduction reaction (e-CO2RR) can offer viable strategies to advance the development of the Reactive Capture of CO2 (RCC). In this report we studied the effect of amines on the performance of the [Co(PDI-Py)] catalyst for the e-CO2RR. The presence of amines shifts the onset potential for the e-CO2RR more positive and increases the catalytic activity while maintaining the high Faradaic efficiency (≥90%) for CO production.

'We thought supporting was strengthening': re-examining the role of external assistance for health systems strengthening in Zimbabwe post-COVID-19.

Zimbabwe has received substantial external assistance for health since the early 2000s, including funding earmarked for, or framed as, health systems strengthening (HSS). This study sought to examine whether external assistance has strengthened the health system (i.e. enabled comprehensive changes to health system performance drivers) or has just supported the health system (by increasing inputs and improving service coverage in the short term). Between August and October 2022, we conducted in-depth key informant interviews with 18 individuals and reviewed documents to understand: (1) whether external funding has supported or strengthened Zimbabwe's health system since the 2000s; (2) whether the experience of COVID-19 fosters a re-examination of what had been considered as HSS during the pre-pandemic era; and (3) areas to be reconsidered for HSS post COVID-19. Our findings suggest that external funders have supported Zimbabwe to control major epidemics and avert health system collapse. However, the COVID-19 pandemic showed that supporting the health system is not the same as strengthening it, as it became apparent at that time that the health sector is plagued with several system-wide bottlenecks. External funding is fragile and highly unsustainable, which reinforces the oft-ignored reality that HSS is a sovereign mandate of country-level authorities, and one that falls outside the core interests of external funders. The key positive lesson from the pandemic is that Zimbabwe is capable of raising domestic resources to fund HSS. However, there is no guarantee that such funding will be maintained. There is a need, then, to reconsider government's stewardship for HSS. External funders need to re-examine whether their funding really strengthens the national health system or just supports the country to provide basic services in their areas of interest.

Malignancy following solid organ transplantation: Current techniques for determination of donor versus recipient origin.

Among the post-transplantation complications that patients may encounter, the transmission of a donor-derived malignant neoplasm is uncommon but potentially life threatening. The determination of donor versus recipient origin is essential particularly in the setting of multiple transplant recipients from the donor. Advances in molecular biology now allow accurate discrimination utilizing routine tissue samples in a timely and cost-effective manner. The techniques are routinely performed in hospital molecular biology laboratories and are also available in commercial labs. The current methodologies are discussed and future possibilities are presented for clinicians caring for solid organ recipients.

Exploring the fragility of meta-analyses in ophthalmology: a systematic review.

OBJECTIVE: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses. METHODS: Meta-analyses of randomized controlled trials with binary outcomes published in a journal classified as 'Ophthalmology' according to the Journal Citation Report or an Ophthalmology-related Cochrane Review were included. An iterative process determined the FI of each meta-analysis. Multivariable linear regression modeling evaluated the relationship between the FI and potential predictive factors in statistically significant and non-significant meta-analyses. RESULTS: 175 meta-analyses were included. The median FI was 6 (Q1-Q3: 3-12). This meant that moving 6 outcomes from one group to another would reverse the study's findings. The FI was 1 for 18 (10.2%) of the included meta-analyses and was ≤5 for 75 (42.4%) of the included meta-analyses. The number of events (p < 0.001) and the p-value (p < 0.001) were the best predictors of the FI in both significant and non-significant meta-analyses. CONCLUSION: The statistical significance of meta-analyses in ophthalmology often hinges on the outcome of a few patients. The number of events and the p-value are the most important factors in determining the fragility of the evidence. The FI is an easily interpretable measure that can supplement the reader's understanding of the strength of the evidence being presented. PROSPERO REGISTRATION: CRD42022377589.

A hypertrophic distal fascicle of the anterior tibiofibular ligament is associated with a high rate of osteochondral lesions of the talus.

PURPOSE: The purpose of this retrospective review was to determine the prevalence of osteochondral lesions (OCLs) of the lateral talar dome in patients with anterior ankle impingement with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament. METHODS: Retrospective chart review identified 40 patients who underwent anterior ankle arthroscopy for the management of anterior ankle impingement. Clinical outcomes assessed included pre- and postoperative foot and ankle outcome score (FAOS), visual analogue scale (VAS), complications, failures, secondary surgical procedures, return-to-work data and return-to-sport data. RESULTS: Thirty-two patients with a mean follow-up time of 29.3 ± 10.4 months were included. The hypertrophic distal fascicle of the anterior tibio-fibular ligament was hypertrophic in 29 patients (90.6%), with a mean thickness of 2.5 ± 0.4 mm on MRI. There were 22 OCLs of the lateral talar dome (75.9%) with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament visualized during arthroscopy. The international cartilage repair society gradings of the lesions included 3 (13.6%) grade I lesions, 15 (68.1%) grade II lesions, 3 (13.6%) grade III lesions, and 1 (4.6%) grade IV lesion. There was a statistically significant improvement in mean FAOS and VAS scores from preoperative to postoperative (p < 0.001). No cases of syndesmotic instability were observed following resection of hypertrophic distal fascicle of the anterior tibio-fibular ligament. CONCLUSION: This retrospective case series demonstrated that a hypertrophic distal fascicle of the anterior tibio-fibular ligament was associated with an OCL of the lateral talar dome identified during arthroscopic evaluation. In addition, preoperative MRI demonstrated poor sensitivity for the detection of these OCLs. Heightened awareness is warranted for potential lateral talar dome OCLs in patients presenting with anterolateral ankle impingement with a hypertrophic ATiFLdf identified on preoperative MRI in the absence of an associated OCLs. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

Impact of COVID-19 on a real-world treat-and-extend regimen with aflibercept for neovascular age-related macular degeneration.

OBJECTIVE: To assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021. METHODS: The primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling. RESULTS: This study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42-70) and 70 (49-90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 µm (P = 0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 µm (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 µm (P < 0.001). CONCLUSIONS: This real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity.

Specific microRNAs in stallion spermatozoa are potential biomarkers of high functionality.

Males of some species, from horses to humans, require medical help for subfertility problems. There is an urgent need for novel molecular assays that reflect spermatozoal function. In the last 25 years, studies examined RNAs in spermatozoa as a window into gene expression during their development and, more recently, for their functions in early embryo development. In clinics, more dense spermatozoa are isolated by density gradient centrifugation before use in artificial insemination to increase pregnancy rates. The objectives of the current study were to discover and quantify the microRNAs in stallion spermatozoa and identify those with differential expression levels in more dense versus less dense spermatozoa. First, spermatozoa from seven stallions were separated into more dense and less dense populations by density gradient centrifugation. Next, small RNAs were sequenced from each of the 14 RNA samples. We identified 287 different mature microRNAs within the 11,824,720 total mature miRNA reads from stallion spermatozoa. The most prevalent was miR-10a/b-5p. The less dense spermatozoa had fewer mature microRNAs and more microRNA precursor sequences than more dense spermatozoa, perhaps indicating that less dense spermatozoa are less mature. Two of the most prevalent microRNAs in more dense stallion spermatozoa were predicted to target mRNAs that encode proteins that accelerate mRNA decay. Nine microRNAs were more highly expressed in more dense spermatozoa. Three of those microRNAs were predicted to target mRNAs that encode proteins involved in protein decay. Both mRNA and protein decay are very active in late spermiogenesis but not in mature spermatozoa. The identified microRNAs may be part of the mechanism to shut down those processes. The microRNAs with greater expression in more dense spermatozoa may be useful biomarkers for spermatozoa with greater functional capabilities.

Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease.

Purpose: Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness. Design: We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system. Participants: Not applicable. Methods: The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these. Main Outcome Measures: Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD. Results: A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome. Conclusion: Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Characterization of a thermostable protease from Bacillus subtilis BSP strain.

This study used conservative one variable-at-a-time study and statistical surface response methods to increase the yields of an extracellular thermostable protease secreted by a newly identified thermophilic Bacillus subtilis BSP strain. Using conventional optimization techniques, physical parameters in submerged fermentation were adjusted at the shake flask level to reach 184 U/mL. These physicochemical parameters were further optimized by statistical surface response methodology using Box Behnken design, and the protease yield increased to 295 U/mL. The protease was purified and characterized biochemically. Both Ca2+ and Fe2+ increased the activity of the 36 kDa protease enzyme. Based on its strong inhibition by ethylenediaminetetracetate (EDTA), the enzyme was confirmed to be a metalloprotease. The protease was also resistant to various organic solvents (benzene, ethanol, methanol), surfactants (Triton X-100), sodium dodecyl sulfate (SDS), Tween 20, Tween-80 and oxidants hydrogen per oxide (H2O2). Characteristics, such as tolerance to high SDS and H2O2 concentrations, indicate that this protease has potential applications in the pharmaceutical and detergent industries.

Inference with cross-lagged effects-Problems in time.

The interpretation of cross-effects from vector autoregressive models to infer structure and causality among constructs is widespread and sometimes problematic. I describe problems in the interpretation of cross-effects when processes that are thought to fluctuate continuously in time are, as is typically done, modeled as changing only in discrete steps (as in e.g., structural equation modeling)-zeroes in a discrete-time temporal matrix do not necessarily correspond to zero effects in the underlying continuous processes, and vice versa. This has implications for the common case when the presence or absence of cross-effects is used for inference about underlying causal processes. I demonstrate these problems via simulation, and also show that when an underlying set of processes are continuous in time, even relatively few direct causal links can result in much denser temporal effect matrices in discrete-time. I demonstrate one solution to these issues, namely parameterizing the system as a stochastic differential equation and focusing inference on the continuous-time temporal effects. I follow this with some discussion of issues regarding the switch to continuous-time, specifically regularization, appropriate measurement time lag, and model order. An empirical example using intensive longitudinal data highlights some of the complexities of applying such approaches to real data, particularly with respect to model specification, examining misspecification, and parameter interpretation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Angina Pectoris Is Associated with Cervical Disc Disease: A Cross-Sectional, Population-Based Study Using the Medicare Expenditure Panel Survey (MEPS).

Atherosclerotic disease in the vessels that supply the cervical spine may lead to degenerative disease. In angina pectoris (AP), atherosclerotic disease leads to coronary vessel occlusion and resulting symptoms. This study aims to determine the relationship between AP and neck pain. Analysis was focused on respondents who had a history of cervical pain disorders, adjusting for demographic, education, and mental health confounders. A total of 30,461 participated in the survey. Of 1,049 respondents, 21% reported neck pain. Mean age of the respondents was 62.6 ± 16.1 years. Nonwhite race, current everyday smokers, lower family income, hypertension, and diabetes had higher prevalence of neck pain (p < 0.05). On multivariate analysis, AP was associated with increased odds of neck pain (odds ratio [OR] = 1.42 [95% confidence interval (CI) 1.04 to 1.92], p = 0.026). AP was independently associated with 42% increased odds of having neck pain. Further study into the association of cardiovascular disease with degenerative disc disease pain should be performed. (Journal of Surgical Orthopaedic Advances 33(2):093-096, 2024).

Direct measurements of neurosteroid binding to specific sites on GABAA receptors.

BACKGROUND AND PURPOSE: Neurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady-state binding affinities of various neurosteroids for specific sites on the GABAA receptor. EXPERIMENTAL APPROACH: Two methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17-methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC-α1GABAAR, a chimeric receptor containing transmembrane domains of the α1-GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions. KEY RESULTS: Allopregnanolone (3α-OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi-allopregnanolone (3ß-OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site-specific probe for the intersubunit site. The affinity and site-specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites. CONCLUSIONS AND IMPLICATIONS: The affinity and specificity of neurosteroid binding to two sites in the ELIC-α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate-reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites.

A study on methods for preimplantation genetic testing (PGT) on in vivo- and in vitro-produced equine embryos, with emphasis on embryonic sex determination.

Two methods for preimplantation genetic testing (PGT) have been described for equine embryos: trophoblast cell biopsy (TCB) or blastocoele fluid aspiration (BFA). While TCB is widely applied for both in vivo- and in vitro-produced embryos, BFA has been mostly utilized for in vivo-produced embryos. Alternative methods for PGT, including analysis of cell-free DNA (CFD) in the medium where in vitro-produced embryos are cultured, have been reported in humans but not for equine embryos. In Experiment 1, in vivo- (n = 10) and in vitro-produced (n = 13) equine embryos were subjected to BFA, cultured for 24 h, then subjected to TCB, and cultured for additional 24 h. No detrimental effect on embryonic diameter or re-expansion rates was observed for either embryo group (P > 0.05). In Experiment 2, the concordance (i.e., agreement on detecting the same embryonic sex using two techniques) among BFA, TCB, and the whole embryo (Whole) was studied by detecting the sex-determining region Y (SRY) or testis-specific y-encoded protein 1 (TSPY) (Y-chromosome), and androgen receptor (AR; X-chromosome) genes using PCR. Overall, a higher concordance for detecting embryonic sex was observed among techniques for in vivo-produced embryos (67-100 %; n = 14 embryos) than for in vitro-produced embryos (31-92 %; n = 13 embryos). The concordance between sample types increased when utilizing TSPY (77-100 %) instead of SRY (31-100 %) as target gene. In Experiment 3, CFD analysis was performed on in vitro-produced embryos to determine embryonic sex via PCR (SRY [Y-chromosome] and amelogenin - AMEL [X- and Y-chromosomes]). Overall, CFD was detected in all medium samples, and the concordance between CFD sample and the whole embryo was 60 % when utilizing SRY and AMEL genes. In conclusion, equine embryos can be subjected to two biopsy procedures (24 h apart) without apparent detrimental effects on embryonic size. For in vivo-, but not for in vitro-produced equine embryos, BFA can be considered a potential alternative to TCB for PGT. Finally, CFD can be further explored as a non-invasive method for PGT in in vitro produced equine embryos.

Pediatric dilated cardiomyopathy: a review of current clinical approaches and pathogenesis.

Pediatric dilated cardiomyopathy (DCM) is a rare, yet life-threatening cardiovascular condition characterized by systolic dysfunction with biventricular dilatation and reduced myocardial contractility. Therapeutic options are limited with nearly 40% of children undergoing heart transplant or death within 2 years of diagnosis. Pediatric patients are currently diagnosed based on correlating the clinical picture with echocardiographic findings. Patient age, etiology of disease, and parameters of cardiac function significantly impact prognosis. Treatments for pediatric DCM aim to ameliorate symptoms, reduce progression of disease, and prevent life-threatening arrhythmias. Many therapeutic agents with known efficacy in adults lack the same evidence in children. Unlike adult DCM, the pathogenesis of pediatric DCM is not well understood as approximately two thirds of cases are classified as idiopathic disease. Children experience unique gene expression changes and molecular pathway activation in response to DCM. Studies have pointed to a significant genetic component in pediatric DCM, with variants in genes related to sarcomere and cytoskeleton structure implicated. In this regard, pediatric DCM can be considered pediatric manifestations of inherited cardiomyopathy syndromes. Yet exciting recent studies in infantile DCM suggest that this subset has a distinct etiology involving defective postnatal cardiac maturation, such as the failure of programmed centrosome breakdown in cardiomyocytes. Improved knowledge of pathogenesis is central to developing child-specific treatment approaches. This review aims to discuss the established biological pathogenesis of pediatric DCM, current clinical guidelines, and promising therapeutic avenues, highlighting differences from adult disease. The overarching goal is to unravel the complexities surrounding this condition to facilitate the advancement of novel therapeutic interventions and improve prognosis and overall quality of life for pediatric patients affected by DCM.

Re-thinking all-cause COVID-19 hospitalizations as a surrogate measure for severe illness in observational surveillance studies.

All-cause COVID-19 hospitalization ≤ 30 days of infection is a common outcome for severe illness in observational/surveillance studies. Milder COVID-19 disease and COVID-19-specific measurements calls for an evaluation of this endpoint. This was a descriptive, retrospective cohort study of adults ≥ 18 who were established in primary care at Veteran Health Administration (VHA) facilities. The outcome was hospitalization within 30 days of a laboratory-confirmed, symptomatic SARS-CoV-2 infection. Between December 15, 2021 and May 1, 2022, a simple random sample of all VA facilities, excluding Puerto Rico or Philippines, was drawn to identify these hospitalized cases and determine whether hospitalization was due to COVID-19-specific causes. A chart review was conducted to record the inpatient clinical team's diagnosis and whether the inpatient team classified the diagnosis as COVID-19 related or not. These data were used to classify hospitalizations as either due to COVID-19-specific causes (direct manifestations of SARS-CoV-2 infection) or non-COVID-19-specific hospitalizations (incidental SARS-CoV-2 infection), A simple random sample of 9966 (12.3%) all-cause hospitalizations (95% CI: 12.1%, 12.5%) was used to select 300 representative patients. Of these, 226/300 (75.3%) were determined to be COVID-19-specific. COVID-19 pneumonia was most common (147/226, 65.0%). The highest proportion of COVID-19-specific hospitalizations occurred among unvaccinated (85.0%), followed by vaccinated but not boosted (73.7%) and boosted (59.4%) (p < 0.001). The proportion of non-COVID-19-specific hospitalizations was higher in the later period (15-30 days: 55.0%) than the early (0-15 days: 22.5%) (p = 0.003). This study supports the outcome of COVID-19-specific hospitalization instead of all-cause hospitalization in observational studies. The earlier outcome period (0-15 days) was less susceptible to potential measurement bias.

Clinical outcomes following transtibial medial meniscal root repair are maintained at long-term follow-up.

PURPOSE: To evaluate long-term outcomes of patients treated with posterior medial meniscal root tear (PMMRT) repair through assessment of functional outcome scores and to identify patient surgical and magnetic resonance imaging (MRI) characteristics associated with improved outcomes. METHODS: This was a single-centre, retrospective study evaluating patients who had undergone a PMMR repair using a transtibial suture pullout technique with two locking cinch sutures. This was performed as a follow-up to previously published 2-year and 5-year outcome studies, using the same cohort. All patients from the prior short-term and midterm studies were invited to participate. Patient-reported outcome (PROs) scores, including the International Knee Documentation Committee (IKDC) and Lysholm scores, were collected. Previously collected demographic data were updated based on review of the electronic medical record. Patient outcomes were assessed preoperatively, as well as at 2-year, 5-year and 8-year postoperatively. MRI outcome measurements were assessed at 2-year and 5-year follow-ups. All statistical analysis was performed using SPSS version 26. RESULTS: Seventeen patients of the original 18 patients (94.4%) were included in the final analysis. Additionally, three patients who had additional ipsilateral surgery were excluded from the analysis of PROs. The IKDC score significantly increased from 44.7 ± 11.6 at preoperative baseline to 71.2 ± 21.3 at 8-year post-operation (p = 0.001). There were no significant differences in IKDC score between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). The Lysholm score significantly increased from 49.6 ± 7.3 at preoperative baseline to 76.4 ± 17.2 at 8-year follow-up (p < 0.001). There was no significant difference in Lysholm scores between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). A linear regression analysis found that 5-year IKDC scores were significantly correlated with 8-year IKDC scores (ß = 0.681, p = 0.038). At 8-year follow-up, four (23.5%) patients required additional procedures on their operative knee (one total knee arthroplasty conversion). CONCLUSION: Patients treated with repair of PMMRT had maintenance of clinical outcome improvements at long-term follow-up despite worsening MRI outcomes at short-term and medium-term follow-ups. While a high proportion of patients required additional procedures on their operative knee at 8-year follow-up, few of these patient's additional procedures were related to failure of their primary surgery. Providers and patients may expect durable clinical outcomes following the repair of PMMRT, irrespective of radiographic appearance. LEVEL OF EVIDENCE: Level IV.

MANAGEMENT OF LARGE FULL-THICKNESS MACULAR HOLES: Long-Term Outcomes of Internal Limiting Membrane Flaps and Internal Limiting Membrane Peels.

BACKGROUND/PURPOSE: To determine and compare the efficacy of a surgical internal limiting membrane (ILM) flap technique with the traditional ILM peel on long-term visual and anatomical outcomes for large (>400 µm) full-thickness macular holes. METHODS: From October 2016 to July 2022, patients undergoing initial full-thickness macular hole repair with the ILM flap or ILM peel technique were reviewed. Final outcomes were recorded and based on size in microns: 401 to 800, 801 to 1,200, and >1,200. RESULTS: Patients treated with ILM flap (n = 52, 94.2% closure rate) or ILM peel (n = 407, 93.6% closure rate) were followed with a mean follow-up time of 15.0 ± 10.2 and 20.0 ± 13.4 months, respectively. Success rates for ILM flaps and ILM peels were compared for full-thickness macular holes of 401 to 800 (100%, 95.8%, P = 0.39), 801 to 1,200 (95%, 93%, P = 0.74), and >1,200 (86.7%, 86.7%, P = 1.0) µm. Mean best-recorded logarithm of the minimal angle of resolution visual acuity for ILM flaps and ILM peels, respectively, was 1.02 ± 0.46 and 0.87 ± 0.47 preoperatively, with follow-up acuity of 0.48 ± 0.32 (P < 0.03) and 0.39 ± 0.42 (P < 0.01) at Year 3. CONCLUSION: Both techniques provide a similar anatomical closure rate and functional improvement in vision. Comparisons should be cautiously made based on difference in preoperative hole size.

Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.