Is Hospital-Based Outpatient Revision Total Knee Arthroplasty Safe? An Analysis of 2,171 Outpatient Aseptic Revision Procedures.

BACKGROUND: Outpatient primary total knee arthroplasty (TKA) has been well-established as a safe and effective procedure; however, the safety of outpatient revision TKA remains unclear. Therefore, this study utilized a large database to compare outcomes between outpatient and inpatient revision TKA. METHODS: An all-payor database was queried to identify patients undergoing revision TKA from 2010 to 2022. Patients who had diagnosis codes related to periprosthetic joint infection (PJI) were excluded. Outpatient surgery was defined as a length of stay < 24 hours. Cohorts were matched by age, sex, Elixhauser Comorbidity Index, comorbidities (diabetes, obesity, tobacco use), components revised (1-versus 2-component), and revision etiology. Medical complications at 90 days and surgical complications at 1 and 2 years postoperatively were evaluated through multivariate logistic regression. A total of 4,342 aseptic revision TKAs were included. RESULTS: No differences in patient characteristics, procedure type, or revision etiologies were seen between groups. The outpatient cohort had a lower risk of PJI (odds ratio (OR): 0.547, 95% confidence interval (CI): 0.337 to 0.869; P = .012), wound dehiscence (OR: 0.393, 95% CI: 0.225 to 0.658; P < .001), transfusion (OR: 0.241, 95% CI: 0.055 to 0.750; P = .027), reoperation (OR: 0.508, 95% CI: 0.305 to 0.822; P = .007), and any complication (OR: 0.696, 95% CI: 0.584 to 0.829; P < .001) at 90 days postoperatively. At 1 year and 2 years postoperatively, outpatient revision TKA patients had a lower incidence of revision for PJI (OR: 0.332, 95% CI: 0.131 to 0.743; P = .011 and OR: 0.446, 95% CI; 0.217 to 0.859; P = .020, respectively) and all-cause revision (OR: 0.518, 95% CI: 0.377 to 0.706; P < .001 and OR: 0.548, 95% CI: 0.422 to 0.712; P < .001, respectively). CONCLUSIONS: Our findings suggest that revision TKA can be safely performed on an outpatient basis in appropriately selected patients who do not have an increased risk of adverse events relative to inpatient revision TKA. However, we could not ascertain case complexity in either cohort, and despite controlling for several potential confounders, other less tangible differences could exist between groups.

Early Prosthetic Hip Dislocation: Does the Timing of the Dislocation Matter?

INTRODUCTION: Early dislocation following total hip arthroplasty (THA) is a common reason for revision. The purpose of this study was to determine if the acuity of the dislocation episode affects the risk of revision surgery. METHODS: A retrospective review of a national, all-payer administrative database comprised of claims from 2010 to 2020 was used to identify patients who had a prosthetic hip dislocation at various post-operative time intervals (0 to 7, 7 to 30, 30 to 60, and 60 to 90 days). Of the 45,352 primary unilateral THA patients who had sufficient follow-up, there were 2,878 dislocations within 90 days. Dislocators were matched 1:1 based on age, sex, and a comorbidity index with a control group (no dislocation). Demographics, surgical indications, comorbidities, ten-year revision rates, and complications were compared among cohorts. Multivariable logistic regression analysis was performed to identify risk factors for revision THA following early dislocation. RESULTS: Among matched cohorts, dislocation at any time interval was associated with significantly increased odds of subsequent 10-year revision (OR [odds ratio] = 25.60 to 33.4, P < 0.001). Acute dislocators within 7 days did not have an increased risk of all cause revisions at 10 years relative to other early dislocators. Revision for indication of instability decreased with time to first dislocation (< 7 days: 85.7% versus 60 to 90 days: 53.9%). Primary diagnoses of post traumatic arthritis (OR = 2.53 [1.84 to 3.49], P < 0.001), hip fracture (OR = 3.8 [2.53 to 5.72], P < 0.001), and osteonecrosis (OR = 1.75 [1.12 to 2.73], P = 0.010) were most commonly associated with revision surgery after an early dislocation. CONCLUSION: Dislocation within 90 days of total hip arthroplasty is associated with increased odds of subsequent revision. Early dislocation within 7 days of surgery has similar all cause revision-free survivorship, but an increased risk of a subsequent revision for instability when compared to patients who dislocated within 7 to 90 days.

Utero-cervical angle to predict the risk of spontaneous preterm birth: a review of literature.

BACKGROUND: The aim of this paper was to evaluate the predictive role of the uterocervical angle (UCA) in spontaneous preterm birth (sPTB). METHODS: A systematic review of the literature was performed including all studies reporting the association between UCA and sPTB. Searches were performed with the use of a combination of keywords: "cervical length," "uterocervical angle," and "preterm birth" from inception of each database to March 2022. The statistical evaluations were carried out using the Comprehensive Meta-Analysis version 3 (Biostat Inc. USA). RESULTS: Sixteen studies all conducted on the second trimester UCA as well as its association with sPTB were included in this study. In all studies the measurements of cervical length (CL) and UCA were performer in the second trimester, except in one that in the third trimester. In most studies the CL is greater than 30 mm and the UCA is greater than 110 °. In seven studies women with symptoms were considered while in 8 studies the women were asymptomatic. CONCLUSIONS: It is too early for it to reach a firm conclusion on UCA utilization in clinical settings. A higher UCA measurement (greater than 150°) is an important risk factor for deliveries before 37 weeks' gestation. It provides a higher diagnostic performance in high risk patients than the CL measurement. However, the most relevant ultrasound parameter for the prediction of delivery within the next few data in women with preterm delivery remains the cervical length. There is a need to consider both markers and create protocols so that the values obtained with UCA and those with CL can make a real contribution to decisions to be made rather than using only CL.

Suppression of anthracnose disease by orsellinaldehyde isolated from the mushroom Coprinus comatus.

AIMS: Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease. METHODS AND RESULTS: The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on mass spectroscopy and nuclear magnetic resonance analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with fluorescein diacetate and propidium iodide demonstrated that the compound is fungicidal. The postharvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively. CONCLUSIONS: Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.

Late Manipulation under Anesthesia after Total Knee Arthroplasty: Improved Range of Motion and a Low Complication Rate.

The purpose of this study was to evaluate outcomes of late manipulation under anesthesia (MUA) for stiffness performed from ≥12 weeks to more than a year after primary total knee arthroplasty (TKA). A total of 152 patients receiving MUA ≥12 weeks after primary TKA from 2014 to 2021 were reviewed. The primary outcome measured was change in range of motion (ROM). We tracked intraoperative complications and the need for repeat MUA or open procedure for continued stiffness after initial MUA. Three subgroups were analyzed: Group 1 included 58 knees between 12 weeks and 6 months after TKA, Group 2 included 44 knees between 6 and 12 months after TKA, and Group 3 included 50 knees ≥12 months after TKA. Analysis included descriptive statistics and univariate analysis, with α <0.05. Groups 1 to 3 all significantly increased their overall ROM by 20.9, 19.2, and 22.0 degrees, respectively. All groups significantly increased their flexion and extension from preoperatively. Group 1 had one intraoperative supracondylar femur fracture (1.7%) requiring open reduction and internal fixation, and five patients required repeat MUA or open procedure (8.6%). Group 2 had no intraoperative fractures, and five patients required repeat MUA or open procedure (11.4%). Group 3 had one intraoperative tibial tubercle avulsion fracture managed conservatively (2.0%) and one repeat MUA (2.0%). Late MUA resulted in significantly improved ROM in all groups. ROM improved more as the time from index TKA increased, although statistically insignificant. Repeat MUA or open procedure rate decreased with MUA ≥12 months from TKA, although statistically insignificant. The overall intraoperative fracture risk was 1.3%.

Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis induced hepatobiliary injury in sickle cell disease.

Sickle cell disease (SCD) associated chronic hemolysis promotes oxidative stress, inflammation and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD related hepatobiliary injury has not been fully elucidated yet. Here, we show that chronic liver injury in SCD patients is associated with elevated levels of hepatic membrane bound CD163. Hemolysis and increase in hepatic heme, hemoglobin and iron levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that HO-1 positively regulates membrane bound CD163 expression independent of NRF2 signaling in SCD liver. We further demonstrate that of the interaction between CD163 and HO-1 is not dependent on CD163-hemoglobin binding. These findings indicate that CD163 is a potential biomarker of SCD associated hepatobiliary injury. Understanding the role of HO-1 in membrane bound CD163 regulation may help identify novel therapeutic targets for hemolysis induced chronic liver injury.

Shoulder Prosthetic Infection and Humerus Osteomyelitis From Cutibacterium Following Eden-Hybinette Procedure.

We describe the case of a patient who recently underwent a guided arthroscopic Eden-Hybinette procedure for the revision of a previous failed procedure of Latarjet and resurgence of shoulder instability. The subsequent development of painful infectious arthritis of the left shoulder complicated by osteomyelitis of the humerus, caused by Cutibacterium acnes, and accompanied by high fever was resolved only after the removal of synthetic screws and bone grafting and thanks to prolonged intravenous antibiotic treatment. The antibiotic regime was continued, both intramuscularly and orally, after discharge, allowing the full healing of the severe osteoarticular infection of the shoulder.

Outcomes after pancreaticoduodenectomy with or without preoperative hyperbaric oxygen therapy.

Background: Hyperbaric oxygen (HBO2) therapy is an alternative method against the deleterious effects of ischemic/reperfusion (I/R) injury and its inflammatory response. This study assessed the effect of preoperative HBO2 on patients undergoing pancreaticoduodenectomy. Study Design: Patients were randomized via a computer-generated algorithm. Patients in the HBO2 cohort received two sessions of HBO2 the evening before and the morning of surgery. Measurements of inflammatory mediators and self-assessed pain scales were determined pre-and postoperatively. In addition, perioperative variables and long-term survival were collected and analyzed. Data are presented as median (mean ± SD). Results: 33 patients were included; 17 received preoperative HBO2, and 16 did not. There were no intraoperative or postoperative statistical differences between patients with or without preoperative HBO2. Erythrocyte sedimentation rate (ESR), IL-6, and IL-10 increased slightly before returning to normal, while TGF-alpha decreased before increasing. However, there were no differences with or without HBO2. At postoperative day 30, the pain level measured with VAS score (Visual Analog Score) was lower after HBO2 (1 ± 1.3 vs. 3 ± 3.0, p=0.05). Eleven (76%) patients in the HBO2 cohort and 12 (75%) patients in the non- HBO2 had malignant pathology. The percentage of positive lymph nodes in the HBO2 was 7% compared to 14% in the non-HBO2 (p<0.001). Overall survival was inferior after HBO2 compared to the non- HBO2 (p=0.03). Conclusions: Preoperative HBO2 did not affect perioperative outcomes or significantly change the inflammatory mediators for patients undergoing robotic pancreaticoduodenectomy. Long-term survival was inferior after preoperative HBO2. Further randomized controlled studies are required to assess the full impact of this treatment on patients' prognosis.

Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.

BACKGROUND: Although nitric oxide based therapeutics have been shown in preclinical models to reduce vaso-occlusive events and improve cardiovascular function, a clinical trial of a phosphodiesterase 5 inhibitor increased rates of admission to hospital for pain. We aimed to examine if riociguat, a direct stimulator of the nitric oxide receptor soluble guanylate cyclase, causes similar increases in vaso-occlusive events. METHODS: This was a phase 1-2, randomised, double blind, placebo-controlled trial. Eligible patients were 18 years or older, had confirmed sickle cell disease documented by haemoglobin electrophoresis or HPLC fractionation (haemoglobin SS, SC, Sß-thalassemia, SD, or SO-Arab), and stage 1 hypertension or proteinuria. Participants were randomly assigned 1:1 to receive either riociguat or matching placebo via a web-based system to maintain allocation concealment. Both treatments were administered orally starting at 1·0 mg three times a day up to 2·5 mg three times a day (highest tolerated dose) for 12 weeks. Dose escalation by 0·5 mg was considered every 2 weeks if systolic blood pressure was greater than 95 mm Hg and the participant had no signs of hypotension; otherwise, the last dose was maintained. The primary outcome was the proportion of participants who had at least one adjudicated treatment-emergent serious adverse event. The analysis was performed by the intention-to-treat. This trial is registered with ClinicalTrials.gov (NCT02633397) and was completed. FINDINGS: Between April 11, 2017, and Dec 31, 2021, 165 participants were screened and consented to be enrolled into the study. Of these, 130 participants were randomly assigned to either riociguat (n=66) or placebo (n=64). The proportion of participants with at least one treatment-emergent serious adverse event was 22·7% (n=15) in the riociguat group and 31·3% (n=20) in the placebo group (difference -8·5% [90% CI -21·4 to 4·5]; p=0·19). A similar pattern emerged in other key safety outcomes, sickle cell related vaso-occlusive events (16·7 [n=11] vs 21·9% [n=14]; difference -5·2% [-17·2 to 6·5]; p=0·42), mean pain severity (3·18 vs 3·32; adjusted mean difference -0·14 [-0·70 to 0·42]; p=0·69), and pain interference (3·15 vs 3·12; 0·04 [-0·62 to 0·69]; p=0·93) at 12 weeks were similar between groups. Regarding the key clinical efficacy endpoints, participants taking riociguat had a blood pressure of -8·20 mm Hg (-10·48 to -5·91) compared with -1·24 (-3·58 to 1·10) in those taking placebo (-6·96 mm Hg (90% CI -10·22 to -3·69; p<0·001). INTERPRETATION: Riociguat was safe and had a significant haemodynamic effect on systemic blood pressure. The results of this study provide measures of effect and variability that will inform power calculations for future trials. FUNDING: Bayer Pharmaceuticals.

Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: A cross-sectional study.

OBJECTIVE: Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. METHODS: In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation. RESULTS: The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. SIGNIFICANCE: This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.

Body Mass Index Does Not Drive the Risk for Early Postoperative Instability After Total Hip Arthroplasty: A Matched Cohort Analysis.

BACKGROUND: Instability remains the leading cause of revision following total hip arthroplasty (THA). The objective of the present investigation was to determine whether an elevated body mass index (BMI) is associated with an increased risk of instability after primary THA. METHODS: An administrative claims database was queried for patients undergoing elective, primary THA for osteoarthritis between 2010 and 2022. Patients who underwent THA for a femoral neck fracture were excluded. Patients who had an elevated BMI were grouped into the following cohorts: 25 to 29.9 (n = 2,313), 30 to 34.9 (n = 2,230), 35 to 39.9 (n = 1,852), 40 to 44.9 (n = 1,450), 45 to 49.9 (n = 752), and 50 to 59.9 (n = 334). Patients were matched 1:1 based on age, sex, and Elixhauser Comorbidity Index, as well as a history of spinal fusion, neurodegenerative disorders, and alcohol abuse, to controls with a normal BMI (20 to 24.9). A multivariate logistic regression controlling for age, sex, Elixhauser Comorbidity Index, and additional risk factors for dislocation was used to evaluate dislocation rates at 30 days, 90 days, 6 months, 1 year, and 2 years. Rates of revision for instability were similarly compared at 1 year and 2 years postoperatively. RESULTS: No significant differences in dislocation rate were observed between control patients and each of the evaluated BMI classes at all evaluated postoperative intervals (all P values > .05). Similarly, the risk of revision for instability was comparable between the normal weight cohort and each evaluated BMI class at 1 year and 2 years postoperatively (all P values > .05). CONCLUSIONS: Controlling for comorbidities and known risk factors for instability, the present analysis demonstrated no difference in rates of dislocation or revision for instability between normal-weight patients and those in higher BMI classes.

Three Differing Methods of Treating Intraoperative Nondisplaced Calcar Fractures Demonstrate Similar Radiographic Stem Subsidence.

BACKGROUND: Several management strategies have been described to treat intraoperative calcar fractures during total hip arthroplasty (THA), including retaining the primary implant and utilizing cerclage cables (CCs) or switching the implant to one that bypasses the fracture and achieves diaphyseal fixation. However, the radiographic and clinical outcomes of these differing strategies have never been described and compared. METHODS: We retrospectively identified 50 patients who sustained an intraoperative calcar fracture out of 9,129 primary total hip arthroplasties (0.55%) performed by one of three surgeons between 2008 and 2022. Each of the three surgeons consistently employed a distinct strategy for the management of these fractures: retention of the primary metaphyseal-engaging implant and placement of CCs; exchange to a modular, tapered-fluted stem (MTF); or exchange to a fully-coated, diaphyseal-engaging stem (FC). Stem subsidence was then evaluated on standing anteroposterior pelvis radiographs at three months and one year postoperatively. Postoperative medical and surgical complication rates were evaluated. RESULTS: A total of fifteen patients were treated with CC, 15 with MTF, and 20 with FC. At three-month follow-up, mean stem subsidence was 0.43 ± 0.08 mm, 1.47 ± 0.36 mm, and 0.68 ± 0.39 mm for CC, MTF, and FC cohorts, respectively (P = .323). At one-year, mean stem subsidence was 0.70 ± 0.08 mm, 1.74 ± 0.69 mm, and 1.88 ± 0.90 mm for the CC, MTF, and FC cohorts, respectively (P = .485). Medical complications included 2 venous thromboembolic events (4%) within 90 days of surgery. There were 6 reoperations (12%); 3 (6%) for acute periprosthetic joint infection (all within the FC cohort); 2 (4%) for postoperative periprosthetic fractures (one fracture distal to the stem in the FC cohort and one fracture at the level of the stem in the MTF cohort), and 1 (2%) closed reduction for instability (within the CC cohort). CONCLUSIONS: The three described methods of managing intraoperative nondisplaced calcar fractures demonstrated little radiographic stem subsidence; however, the risk of reoperation was much higher than expected.

Risk of Subsequent Fusion After Isolated Decompression of Lumbar Facet Cysts.

INTRODUCTION: Lumbar facet cysts represent a potential source of nerve root compression in elderly patients. Isolated decompression without fusion has proven to be a reasonable treatment option in properly indicated patients. However, the risk of lumbar fusion after isolated decompression and facet cyst excision has yet to be elucidated. METHODS: The PearlDiver database was reviewed for patients undergoing isolated laminectomy for lumbar facet cyst from January 2015 to December 2018 using Current Procedural Terminology coding. Patients undergoing concomitant fusion or additional decompression, as well as those diagnosed with preexisting spondylolisthesis or without a minimum of 5-year follow-up, were excluded. Rates of subsequent lumbar fusion and potential risk factors for subsequent fusion were identified. Statistical analysis included descriptive statistics, chi square test, and multivariate logistic regression. Results were considered significant at P < 0.05. RESULTS: In total, 10,707 patients were ultimately included for analysis. At 5-year follow-up, 727 (6.79%) of patients underwent subsequent lumbar fusion after initial isolated decompression. Of these, 301 (2.81% of total patients, 41.4% of fusion patients) underwent fusion within the first year after decompression. Multivariate analysis identified chronic kidney disease, hypertension, and osteoarthritis as risk factors for requiring subsequent lumbar fusion at 5 years following the index decompression procedure ( P < 0.033; all). CONCLUSION: Patients undergoing isolated decompression for lumbar facet cysts undergo subsequent lumbar fusion at a 5-year rate of 6.79%. Risk factors for subsequent decompression include chronic kidney disease, hypertension, and osteoarthritis. This study will assist spine surgeons in appropriately counseling patients on expected postoperative course and potential risks of isolated decompression.

Warm autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurring after COVID19 infection and administration of Casirivimab + Imdevimab (COVID19 monoclonal antibody).

Warm Autoimmune Hemolytic Anemia (WAHA) is the most common form of autoimmune hemolysis and there is a growing body of evidence of an association between SARS-CoV-2 infection, WAHA and a hyperinflammatory state, including hemophagocytic lymphohistiocytosis/macrophage activation syndrome. However, there is no literature to date of WAHA or hyperinflammatory state following administration of anti-SARS-CoV-2 monoclonal antibody treatment. This report documents a case of a patient with history of WAHA who developed brisk hemolysis and a hyperinflammatory state consistent with hemophagocytic lymphohistiocytosis/macrophage activation syndrome after COVID-19 infection and treatment with an anti-SARS-CoV-2 monoclonal antibody. He was successfully treated with multimodal treatment involving steroids, intravenous immunoglobulins, rituximab, anakinra, and vincristine with resolution of the hemolysis.

Preoperative Corticosteroid Injections Are Not Associated with Deep Infection after Unicompartmental Knee Arthroplasty.

Prior to unicompartmental knee arthroplasty (UKA), corticosteroid injections (CSI) are a common nonoperative treatment for arthritis. It is unclear whether CSI prior to UKA impacts the likelihood of postoperative infection. This study sought to determine if there is a time- and/or dose-dependent relationship between preoperative CSI and postoperative infection. An administrative claims database was queried for patients undergoing UKA with more than 1 year of pre-enrollment and follow-up. Of 31,676 patients with a UKA who met enrollment criteria, 8,628 patients had a CSI 0 to 3 months prior to surgery, 111 had a CSI 3 to 12 months prior to surgery, and 22,937 never received an injection. Overall, 246 postoperative deep infections were reported (0.8%). Time-dependent and dose-dependent relationships were modeled using multivariable logistic regressions. Postoperative deep infections occurred in 64 patients with CSI 0 to 3 months prior to surgery (0.7%), compared with 0 patients with CSI 3 to 12 months before surgery (0.0%) and 182 controls (0.8%, p = 0.58). CSI within 1 month prior to UKA was not statistically associated with postoperative infection (p = 0.66). Two or more CSI within 3 months prior to UKA were associated with a twofold elevated odds of infection, compared with receiving a single injection (odds ratio [OR]: 2.08, p = 0.03). Univariable predictors of infection included younger age, increasing Charlson Comorbidity Index, smoking, asthma, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, liver disease, and obesity. Multivariable analysis controlling for these characteristics elicited no relationship between recent CSI administration and postoperative infection. CSI within 3 months of surgery (1.5%) or 3 to 12 months (1.8%) were associated with increased conversion to total knee arthroplasty (TKA) compared with those who did not receive an injection (1.1%, p = 0.01), although TKA for indication of periprosthetic joint infection was not statistically different (p = 0.72). Preoperative CSI within 3 months of UKA is not associated with postoperative infection, although significant medical comorbidity does show an association. Preoperative CSI is associated with increased conversion from UKA to TKA for noninfectious indications.

Identification of two phthalide derivatives and an oxindole compound isolated from the edible mushroom Pleurotus ostreatus and their inhibitory activities against plant pathogenic microorganisms.

The excessive use of chemical pesticides in agricultural fields for controlling plant pathogenic microorganisms harms human health, the environment, and other beneficial microorganisms in the soil and plants. To address this challenge, it is essential to isolate and discover bioactive compounds from biological resources that could inhibit plant pathogenic microorganisms. In this study, the culture filtrate of the edible mushroom Pleurotus ostreatus was subjected to bioassay-guided isolation, and two phthalide derivatives-4,6-dimethoxyphthalide (1) and 5,7-dimethoxyphthalide (2)-were identified, along with an oxindole compound-3-hydroxy-3-methyloxindole (3). The inhibitory activities of the three compounds were evaluated against four fungal and five bacterial pathogens. Remarkably, 1 and 2 exhibited the lowest IC50 values against the conidial germination and germ tube elongation of the rice blast fungus Pyricularia oryzae. However, their effectiveness against bacterial pathogens was relatively low. The (S) and (R)-enantiomers of 3-hydroxy-3-methyloxindole showed different activities against plant fungal pathogens and bacterial plant pathogens.

Star-Shaped Space of Solutions of the Spherical Negative Perceptron.

Empirical studies on the landscape of neural networks have shown that low-energy configurations are often found in complex connected structures, where zero-energy paths between pairs of distant solutions can be constructed. Here, we consider the spherical negative perceptron, a prototypical nonconvex neural network model framed as a continuous constraint satisfaction problem. We introduce a general analytical method for computing energy barriers in the simplex with vertex configurations sampled from the equilibrium. We find that in the overparametrized regime the solution manifold displays simple connectivity properties. There exists a large geodesically convex component that is attractive for a wide range of optimization dynamics. Inside this region we identify a subset of atypical high-margin solutions that are geodesically connected with most other solutions, giving rise to a star-shaped geometry. We analytically characterize the organization of the connected space of solutions and show numerical evidence of a transition, at larger constraint densities, where the aforementioned simple geodesic connectivity breaks down.

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease.

Sickle cell disease (SCD) is a monogenic disorder that affects 100,000 African Americans and millions of people worldwide. Intra-erythrocytic polymerization of sickle hemoglobin (HbS) promotes erythrocyte sickling, impaired rheology, ischemia and hemolysis, leading to the development of progressive liver injury in SCD. Liver resident macrophages and monocytes are known to enable the clearance of HbS, however, the role of liver sinusoidal endothelial cells (LSECs) in HbS clearance and liver injury in SCD remains unknown. Using real-time intravital (in vivo) imaging in the mice liver as well as flow cytometric analysis and confocal imaging of primary human LSECs, we show for the first time that liver injury in SCD is associated with accumulation of HbS and iron in the LSECs, leading to LSEC senescence. Hb uptake by LSECs was mediated by micropinocytosis. Hepatic monocytes were observed to attenuate LSECsenescence by accelerating HbS clearance in the liver of SCD mice, however, this protection was impaired in P-selectin-deficient SCD mice secondary to reduced monocyte recruitment in the liver. These findings are the first to suggest that LSECs contribute to HbS clearance and HbS induced LSEC-senescence promotes progressive liver injury in SCD mice. Our results provide a novel insight into the pathogenesis of hemolysis induced chronic liver injury in SCD caused by LSEC senescence. Identifying the regulators of LSEC mediated HbS clearance may lead to new therapies to prevent the progression of liver injury in SCD.

Use of Disease-Modifying Treatments in Patients With Sickle Cell Disease.

Importance: Despite hydroxyurea being an established treatment for sickle cell disease (SCD), it remains underused. The recent approval of the disease-modifying treatments (DMTs) l-glutamine, crizanlizumab, and voxelotor underscores the need to understand the uptake of DMTs in the current treatment landscape. Objective: To explore characteristics that may be associated with DMT use and to describe observed patterns of yearly DMT use from 2014 to 2021. Design, Setting, and Participants: This cross-sectional study used administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 1, 2014, to September 30, 2021, to identify adults and children with SCD. Data were analyzed from August 1, 2022, to August 28, 2023. Exposure: Use of DMTs. Main Outcomes and Measures: Patient characteristics across groups with varying patterns of DMT use and yearly patterns of prescription fills for hydroxyurea, crizanlizumab, voxelotor, and l-glutamine. Results: A total of 5022 beneficiaries with SCD (2081 [41.4%] aged 18-45 years; 2929 [58.3%] female) were included in sample A (144 [2.9%] inconsistent users, 274 [5.5%] incident users, 892 [17.8%] consistent users, and 3712 [73.9%] non-DMT users). Inconsistent users had a higher prevalence of vaso-occlusive crises (mean [SD], 3.7 [4.7]), splenic complications (6 of 144 [4.2%]), pulmonary complications (36 of 144 [25.0%]), kidney disease (21 of 144 [14.6%]), acute chest syndrome (18 of 144 [12.5%]), and health care visits (eg, mean [SD] inpatient visits, 7.0 [10.7]) compared with the other use groups. Non-DMT users had the lowest prevalence of vaso-occlusive crises (mean [SD], 0.8 [2.4]), acute chest syndrome (109 of 3712 [2.9%]), and inpatient (mean [SD], 2.0 [6.6]) and emergency department (mean [SD], 0.7 [3.1]) visits and the highest proportion of adults 65 years and older (593 of 3712 [16.0%]). In sample B (6387 beneficiaries with SCD), hydroxyurea use modestly increased from 428 of 2188 participants (19.6%) in 2014 to 701 of 2880 (24.3%) in 2021. Use of l-glutamine increased briefly but gradually decreased throughout the study period. In 2021, out of 2880 participants, 102 (3.5%) had at least 1 fill for crizanlizumab and 131 (4.6%) had at least 1 fill for voxelotor. Overall, total DMT use increased from 428 of 2188 participants (19.6%) in 2014 to 815 of 2880 patients (28.3%) in 2021. Conclusions and Relevance: In this cross-sectional analysis of adults and children with SCD, uptake of DMTs remained low from 2014 to 2021, despite the approval of newer therapies. Notable differences in patient characteristics across varied DMT exposure types necessitate further exploration into factors that facilitate DMT use and the creation of strategies to enhance DMT uptake.