Tumor suppressor Par-4 activates autophagy-dependent ferroptosis.

Ferroptosis is a unique iron-dependent form of non-apoptotic cell death characterized by devastating lipid peroxidation. Whilst growing evidence suggests that ferroptosis is a type of autophagy-dependent cell death, the underlying molecular mechanisms regulating ferroptosis are largely unknown. In this study, through an unbiased RNA-sequencing screening, we demonstrate the activation of a multi-faceted tumor-suppressor protein Par-4/PAWR during ferroptosis. Functional studies reveal that genetic depletion of Par-4 effectively blocks ferroptosis, whereas Par-4 overexpression sensitizes cells to undergo ferroptosis. More importantly, we have determined that Par-4-triggered ferroptosis is mechanistically driven by the autophagic machinery. Upregulation of Par-4 promotes activation of ferritinophagy (autophagic degradation of ferritin) via the nuclear receptor co-activator 4 (NCOA4), resulting in excessive release of free labile iron and, hence, enhanced lipid peroxidation and ferroptosis. Inhibition of Par-4 dramatically suppresses the NCOA4-mediated ferritinophagy signaling axis. Our results also establish that Par-4 activation positively correlates with reactive oxygen species (ROS) production, which is critical for ferritinophagy-mediated ferroptosis. Furthermore, Par-4 knockdown effectively blocked ferroptosis-mediated tumor suppression in the mouse xenograft models. Collectively, these findings reveal that Par-4 has a crucial role in ferroptosis, which could be further exploited for cancer therapy.

FAIR compliant database development for human microbiome data samples.

Introduction: Sharing microbiome data among researchers fosters new innovations and reduces cost for research. Practically, this means that the (meta)data will have to be standardized, transparent and readily available for researchers. The microbiome data and associated metadata will then be described with regards to composition and origin, in order to maximize the possibilities for application in various contexts of research. Here, we propose a set of tools and protocols to develop a real-time FAIR (Findable. Accessible, Interoperable and Reusable) compliant database for the handling and storage of human microbiome and host-associated data. Methods: The conflicts arising from privacy laws with respect to metadata, possible human genome sequences in the metagenome shotgun data and FAIR implementations are discussed. Alternate pathways for achieving compliance in such conflicts are analyzed. Sample traceable and sensitive microbiome data, such as DNA sequences or geolocalized metadata are identified, and the role of the GDPR (General Data Protection Regulation) data regulations are considered. For the construction of the database, procedures have been realized to make data FAIR compliant, while preserving privacy of the participants providing the data. Results and discussion: An open-source development platform, Supabase, was used to implement the microbiome database. Researchers can deploy this real-time database to access, upload, download and interact with human microbiome data in a FAIR complaint manner. In addition, a large language model (LLM) powered by ChatGPT is developed and deployed to enable knowledge dissemination and non-expert usage of the database.

Postoperative Vitamin D Surveillance and Supplementation in Revision Total Knee Arthroplasty Patients: A Retrospective Cohort Analysis.

This study was a retrospective cohort analysis of 20 patients who underwent 23 revision total knee arthroplasty procedures in a single geographic region of the United States from January 2015 to February 2023. We analyzed their 25-OH vitamin D levels preoperatively and postoperatively at 1 month, 3 months, 6 months, 1 year, and 2 years. We categorized their supplementation regimens by dose: none, low dose (1000 IU and below), medium dose (1001-5000 IU), and high dose (>5000 IU). We found that there was a high incidence of vitamin D deficiency in this patient population.

Directly visualizing individual polyorganophosphazenes and their single-chain complexes with proteins.

Polyorganophosphazenes are water-soluble macromolecules with immunoadjuvant activity that self-assemble with proteins to enable biological functionality. Direct imaging by cryogenic electron microscopy uncovers the coil structure of those highly charged macromolecules. The successful visualization of individual polymer chains within the vitrified state is achieved in the absence of additives for contrast enhancement and is attributed to the high mass contrast of the inorganic backbone. Upon assembly with proteins, multiple protein copies bind at the single polymer chain level resulting in structures reminiscent of compact spherical complexes or stiffened coils. The outcome depends on protein characteristics and cannot be deduced by commonly used characterization techniques, such as light scattering, thus revealing direct morphological insights crucial for understanding biological activity. Atomic force microscopy supports the morphology outcomes while advanced analytical techniques confirm protein-polymer binding. The chain visualization methodology provides tools for gaining insights into the processes of supramolecular assembly and mechanistic aspects of polymer enabled vaccine delivery.

Patient reported outcome measures (PROMs) as primary and secondary outcomes in total hip and knee arthroplasty randomized controlled trials: a systematic review.

BACKGROUND: Significant heterogeneity exists regarding patient reported outcome measures (PROMs) used in total hip (THA) and knee (TKA) arthroplasty randomized controlled trials (RCTs). This study investigates the PROMs used as primary and secondary outcomes in contemporary arthroplasty RCTs. METHODS: A literature search identified THA and TKA RCTs that were published in top ten impact factor orthopaedic journals from 2017 to 2021. Screening identified 241 trials: 76 THA, 157 TKA, and eight combined. Data were extracted to identify PROMs utilized as either primary or secondary outcomes and the time period of measurement. RESULTS: Visual Analog Scale (VAS) Pain was the most reported primary PROM in THA (9.2%) and TKA (22.9%) trials. This was followed by Numeric Rating Scale (NRS) Pain (7.9%) and the Harris Hip score (6.6%) in THA trials and NRS Pain (4.5%) and the Knee Society score (4.5%) in TKA trials. Many THA (37.0%) and TKA (52.1%) trials did not clearly specify primary outcome time points. Only pain scales were reported at time points less than one week, while various joint-specific functional outcomes were reported at later time points. As secondary outcomes, the Harris Hip score (28.9%) was most common in THA trials and the Knee Society score (26.1%) was most common in TKA trials. Indeterminate primary or secondary outcomes were reported in 18.2% of studies. CONCLUSIONS: Contemporary THA and TKA trials exhibit heterogeneity of PROMs as study outcomes after the first postoperative week. Our findings highlight the need for consensus in PROM reporting and better methodological reporting to improve the interpretability of RCT outcomes. PROSPERO REGISTRATION NUMBER: CRD42022337255.

Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine.

Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved molecular and metabolomic understanding of various diseases, including cancer. In addition, three-dimensional (3-D) disease models have been efficiently utilized for understanding disease pathophysiology and as screening tools in drug discovery. An integrated approach utilizing pan-omics technologies and 3-D in vitro tumor models has led to improved understanding of the intricate network encompassing various signalling pathways and molecular cross-talk in solid tumors. In the present review, we underscore the current trends in omics technologies and highlight their role in understanding genotypic-phenotypic co-relation in cancer with respect to 3-D in vitro tumor models. We further discuss the challenges associated with omics technologies and provide our outlook on the future applications of these technologies in drug discovery and precision medicine for improved management of cancer.

Racial and Ethnic Minority Patients Have Increased Complication Risks When Undergoing Surgery While Not Meeting Clinical Guidelines.

BACKGROUND: Clinical guidelines for performing total joint arthroplasty (TJA) have not been uniformly adopted in practice because research has suggested that they may foster inequities in surgical access, potentially disadvantaging minority sociodemographic groups. The aim of this study was to assess whether undergoing TJA without meeting clinical guidelines affects complication risk and leads to disparities in postoperative outcomes. METHODS: This retrospective cohort study evaluated the records of 11,611 adult patients who underwent primary TJA from January 1, 2010, to December 31, 2020, at an academic hospital network. Based on self-reported race and ethnicity, 89.5% of patients were White, 3.5% were Black, 2.9% were Hispanic, 1.3% were Asian, and 2.8% were classified as other. Patients met institutional guidelines for undergoing TJA if they had a hemoglobin A1c of <8.0% and a body mass index of <40 kg/m 2 and were not currently smoking. A logistic regression model was utilized to identify factors associated with complications, and a mixed-effects model was utilized to identify factors associated with not meeting guidelines for undergoing TJA. RESULTS: During the study period, 11% (1,274) of the 11,611 adults who underwent primary TJA did not meet clinical guidelines. Compared with the group who met guidelines, the group who did not had higher proportions of Black patients (3.2% versus 6.0%; p < 0.001) and Hispanic patients (2.7% versus 4.6%; p < 0.001). An increased risk of not meeting guidelines at the time of surgery was demonstrated among Black patients (odds ratio [OR], 1.60 [95% confidence interval (CI), 1.22 to 2.10]; p = 0.001) and patients insured by Medicaid (OR, 1.75 [95% CI, 1.26 to 2.44]; p = 0.001) or Medicare (OR, 1.22 [95% CI, 1.06 to 1.41]; p = 0.007). Patients who did not meet guidelines had a higher risk of reoperation than those who met guidelines (7.7% [98] versus 5.9% [615]; p = 0.017), including a higher risk of infection-related reoperation (3.1% [40] versus 1.4% [147]; p < 0.001). CONCLUSIONS: We found that patients who underwent TJA despite not meeting institutional preoperative criteria had a higher risk of postoperative complications. These patients were more likely to be from racial and ethnic minority groups, to have a lower socioeconomic status, and to have Medicare or Medicaid insurance. These findings underscore the need for surgery-related shared decision-making that is informed by evidence-based guidelines in order to reduce complication burden. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Peripheral defocus of monofocal intraocular lenses.

PURPOSE: To quantify the angular dependence of monofocal intraocular lens (IOL) power. SETTING: Ophthalmic Biophysics Laboratory, Kallam Anji Reddy campus, L V Prasad Eye Institute, Hyderabad, India. DESIGN: Laboratory study. METHODS: Experiments were performed on IOLs from 2 different manufacturers (APPALENS 207, Appasamy Associates and SN60WF, Alcon Laboratories, Inc.). IOL powers ranged from 17 to 25 diopters (D). The IOLs were mounted in a fluid-filled chamber, and the on-axis and off-axis powers were measured using a laser ray tracing system over the central 3 mm zone with delivery angles ranging from -30 to +30 degrees in 5-degree increments. The position of the best focus was calculated for each IOL at each angle. The angular dependence of IOL power was compared with theoretical predictions. RESULTS: Peripheral defocus increased significantly with increasing incidence angle and power. The peripheral defocus at ±30 degrees increased from 5.8 to 8.5 D when the power increased from 17.5 to 24.5 D for APPALENS 207 and from 4.9 to 7.4 D when the power increased from 17 to 25 D for SN60WF. The mean difference between the measured and theoretical tangential power at ±30 degrees was 0.50 ± 0.16 D for the APPALENS 207 and -0.40 ± 0.10 D for the SN60WF, independent of IOL power. CONCLUSIONS: IOLs introduce a significant amount of peripheral defocus which varies significantly with IOL power and design. Given that peripheral defocus is related to lens power, replacement of the crystalline lens (approximately 24 D) with an IOL will produce a significant difference in peripheral defocus profile after surgery.

An in silico modeling approach to understanding the dynamics of the post-burn immune response.

Introduction: Burns are characterized by a massive and prolonged acute inflammation, which persists for up to months after the initial trauma. Due to the complexity of the inflammatory process, Predicting the dynamics of wound healing process can be challenging for burn injuries. The aim of this study was to develop simulation models for the post-burn immune response based on (pre)clinical data. Methods: The simulation domain was separated into blood and tissue compartments. Each of these compartments contained solutes and cell agents. Solutes comprise pro-inflammatory cytokines, anti-inflammatory cytokines and inflammation triggering factors. The solutes diffuse around the domain based on their concentration profiles. The cells include mast cells, neutrophils, and macrophages, and were modeled as independent agents. The cells are motile and exhibit chemotaxis based on concentrations gradients of the solutes. In addition, the cells secrete various solutes that in turn alter the dynamics and responses of the burn wound system. Results: We developed an Glazier-Graner-Hogeweg method-based model (GGH) to capture the complexities associated with the dynamics of inflammation after burn injuries, including changes in cell counts and cytokine levels. Through simulations from day 0 - 4 post-burn, we successfully identified key factors influencing the acute inflammatory response, i.e., the initial number of endothelial cells, the chemotaxis threshold, and the level of chemoattractants. Conclusion: Our findings highlight the pivotal role of the initial endothelial cell count as a key parameter for intensity of inflammation and progression of acute inflammation, 0 - 4 days post-burn.

Infantile Myofibromatosis of the Femoral Neck: A Case Report.

CASE: A 15-month-old boy who was being followed for developmental dysplasia of the hip because of breech presentation was discovered to have a solitary infantile myofibroma in the left femoral neck. The patient was avoiding weight-bearing on the affected extremity; thus, stabilization of the femoral neck was performed using a proximal femur locking plate. Postoperatively, he achieved all gross motor developmental milestones. CONCLUSION: This report is the first to describe a solitary infantile myofibroma in the femoral neck and demonstrates the utility of operative stabilization of these lesions.

Current concepts in the management of cataract with keratoconus.

This review analyzed all pertinent articles on keratoconus (KCN) and cataract surgery. It covers preoperative planning, intraoperative considerations, and postoperative management, with the aim of providing a simplified overview of treating such patients. Preoperatively, the use of corneal cross-linking, intrastromal corneal ring segments, and topo-guided corneal treatments can help stabilize the cornea and improve the accuracy of biometric measurements. It is important to consider the advantages and disadvantages of traditional techniques such as penetrating keratoplasty and deep anterior lamellar keratoplasty, as well as newer stromal augmentation techniques, to choose the most appropriate surgical approach. Obtaining reliable measurements can be difficult, especially in the advanced stages of the disease. The choice between toric and monofocal intraocular lenses (IOLs) should be carefully evaluated. Monofocal IOLs are a better choice in patients with advanced disease, and toric lenses can be used in mild and stable KCN. Intraoperatively, the use of a rigid gas permeable (RGP) lens can overcome the challenge of image distortion and loss of visual perspective. Postoperatively, patients may need updated RGP or scleral lenses to correct the corneal irregular astigmatism. A thorough preoperative planning is crucial for good surgical outcomes, and patients need to be informed regarding potential postoperative surprises. In conclusion, managing cataracts in KCN patients presents a range of challenges, and a comprehensive approach is essential to achieve favorable surgical outcomes.

Reverse Fragility Index: Comparing Revision Rates Between Direct Anterior and Other Approaches in Total Hip Arthroplasty. A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.

Disparities in Demographics in Hip Arthroplasty Between U.S. Active Duty Military and the ACS-NSQIP Clinical Registry.

INTRODUCTION: Patient demographics, such as sex and age, are known risk factors for undergoing revision following primary total hip arthroplasty (THA). The military population is unique because of the increased rates of primary and secondary osteoarthritis of the hip. Treatment options are limited for returning patients to their line of duty; however, THA has been shown to be an effective option. The primary purpose of this study was to evaluate and contrast the demographic differences of patients undergoing primary THA between the U.S. active duty military population and the general population. The secondary goal was to identify the proportion of primary THA performed at the MTF within the military health system (MHS). METHODS: This was an exempt study determined by the local institutional review board. A retrospective analysis of the MHS Data Repository (MDR) and the National Surgical Quality Improvement Program (NSQIP) was performed. The databases were used to identify the patients who underwent THA from January 1, 2015 to December 31, 2020. The MDR was used to identify demographics such as sex, age, setting of surgery, geographic location, previous military deployments, history of deployment-related injuries, branch of service, and rank. The NSQIP database was queried for sex and age. The median age of the population was compared using the Mann-Whitney U test and gender was compared using the Chi-square test. RESULTS: The MDR was used to evaluate 2,734 patients, whereas the NSQIP database was used to evaluate 223,832 patients. In the military population, patients who underwent THA were 87.7% male with an average age of 45 years, whereas in the general population as measured via the NSQIP database, 45.2% patients were male with an average age of 66.0 years. Comparing the two groups, we demonstrated that the military patients were significantly more likely to be younger (P < .001) and males (P < .001). Only 29.6% of primary THAs were performed within the MTF. CONCLUSIONS: Patients in the MHS are undergoing THA at a younger age and are more likely to be male compared to the general population. A significant portion of primary THAs in the MHS are also being performed at civilian institutions. These demographics may result in increased risk of revision; however, long-term studies are warranted to evaluate survivorship in this unique population.

Discovery and validation of genes driving drug-intake and related behavioral traits in mice.

Substance use disorders are heritable disorders characterized by compulsive drug use, the biological mechanisms for which remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference and sensation seeking, are predictive of drug-use phenotypes, thereby implicating shared genetic mechanisms. High-throughput behavioral screening in knockout (KO) mice allows efficient discovery of the function of genes. We used this strategy in two rounds of candidate prioritization in which we identified 33 drug-use candidate genes based upon predisposing drug-naïve phenotypes and ultimately validated the perturbation of 22 genes as causal drivers of substance intake. We selected 19/221 KO strains (8.5%) that had a difference from control on at least one drug-naïve predictive behavioral phenotype and determined that 15/19 (~80%) affected the consumption or preference for alcohol, methamphetamine or both. No mutant exhibited a difference in nicotine consumption or preference which was possibly confounded with saccharin. In the second round of prioritization, we employed a multivariate approach to identify outliers and performed validation using methamphetamine two-bottle choice and ethanol drinking-in-the-dark protocols. We identified 15/401 KO strains (3.7%, which included one gene from the first cohort) that differed most from controls for the predisposing phenotypes. 8 of 15 gene deletions (53%) affected intake or preference for alcohol, methamphetamine or both. Using multivariate and bioinformatic analyses, we observed multiple relations between predisposing behaviors and drug intake, revealing many distinct biobehavioral processes underlying these relationships. The set of mouse models identified in this study can be used to characterize these addiction-related processes further.

Hippocampus Glutathione S Reductase Potentially Confers Genetic Resilience to Cognitive Decline in the AD-BXD Mouse Population.

Alzheimer's disease (AD) is a prevalent and costly age-related dementia. Heritable factors account for 58-79% of variation in late-onset AD, but substantial variation remains in age-of- onset, disease severity, and whether those with high-risk genotypes acquire AD. To emulate the diversity of human populations, we utilized the AD-BXD mouse panel. This genetically diverse resource combines AD genotypes with multiple BXD strains to discover new genetic drivers of AD resilience. Comparing AD-BXD carriers to noncarrier littermates, we computed a novel quantitative metric for resilience to cognitive decline in the AD-BXDs. Our quantitative AD resilience trait was heritable and genetic mapping identified a locus on chr8 associated with resilience to AD mutations that resulted in amyloid brain pathology. Using a hippocampus proteomics dataset, we nominated the mitochondrial glutathione S reductase protein (GR or GSHR) as a resilience factor, finding that the DBA/2J genotype was associated with substantially higher GR abundance. By mapping protein QTLs (pQTLs), we identified synaptic organization and mitochondrial proteins coregulated in trans with a cis-pQTL for GR. We found four coexpression modules correlated with the quantitative resilience score in aged 5XFAD mice using paracliques, which were related to cell structure, protein folding, and postsynaptic densities. Finally, we found significant positive associations between human GSR transcript abundance in the brain and better outcomes on AD-related cognitive and pathology traits in the Religious Orders Study/Memory and Aging project (ROSMAP). Taken together, these data support a framework for resilience in which neuronal antioxidant pathway activity provides for stability of synapses within the hippocampus.

Genetic variation in DNA damage response pathway and response to Gemtuzumab Ozogamicin in pediatric AML: a report from the Children's Oncology Group.

PURPOSE: Comprehensive pharmacogenomics (PGx) evaluation of calicheamicin-pathway to identify predictive PGx markers of response to gemtuzumab ozogamicin (GO) treatment in acute myeloid leukemia (AML). PATIENTS AND METHODS: Single nucleotide polymorphisms (SNPs) in DNA-damage response (DDR) pathway genes were tested for association with event-free survival (EFS), overall-survival (OS), risk of relapse after induction 1 (RR1) in patients treated with standard chemotherapy consisting of Ara-C, Daunorubicin and Etoposide (ADE) with or without addition of GO on COG-AAML03P1 and COG-AAAML0531 trials (ADE+GO, n=755; ADE n=470). SNPs with significant association with any endpoint within ADE+GO arm but not in the ADE arm were tested using multi-SNP modeling to develop DDR_PGx7 Score. RESULTS: Patients with low-DDR_PGx7 score (<0) had significantly worse EFS (HR=1.51, 95%CI (1.21-1.89), P<0.001), worse OS (HR=1.59, 95%CI (1.22-2.08), P<0.001), and higher RR1 (HR=1.87, 95%CI(1.41-2.47), P<0.0001) compared to patients with high-DDR_PGx7 score (≥0) when treated with GO (ADE+GO cohort). However, no difference between low and high DDR_PGx7 score groups was observed for EFS, OS, and RR1 (all P>0.3) in patients treated on ADE arm. CONCLUSIONS: Our results suggest that DDR pathway-based pharmacogenomic score holds potential to predict outcome in patients treated with GO which consists of DNA damaging cytotoxin, calicheamicin. The potential clinical relevance for this score to personalize GO in AML requires further validation in independent and expanded cohorts.

GenomeMUSter mouse genetic variation service enables multitrait, multipopulation data integration and analysis.

Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease mouse models, mapping populations, and sensitized backgrounds for engineered mutations. The genome sequences of inbred strains, along with dense genotypes from others, enable integrated analysis of trait-variant associations across populations, but these analyses are hampered by the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense variant resource by harmonizing multiple data sets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extendable to other model organisms. The result is a web- and programmatically accessible data service called GenomeMUSter, comprising single-nucleotide variants covering 657 strains at 106.8 million segregating sites. Interoperation with phenotype databases, analytic tools, and other resources enable a wealth of applications, including multitrait, multipopulation meta-analysis. We show this in cross-species comparisons of type 2 diabetes and substance use disorder meta-analyses, leveraging mouse data to characterize the likely role of human variant effects in disease. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.

Patients With Significant Medical Comorbidities May Benefit from Unicompartmental Knee Arthroplasty Over Total Knee Arthroplasty.

Many studies have compared outcomes in total knee arthroplasty (TKA) versus unicompartmental knee arthroplasty (UKA); however, to the authors' knowledge, there is no study evaluating complication rates in patients with significant comorbidities. The purpose of this retrospective study was to compare the incidence of postoperative complications, readmission and reoperation rates, length of stay (LOS), and discharge location for patients with significant medical comorbidities undergoing TKA versus UKA. Using the NSQIP database from 2008 to 2018, patients were identified by CPT code (27447 or 27446) and admission diagnostic code of primary osteoarthritis and included in the study if they had an American Society of Anesthesia score greater than or equal to 3. Chi-square test was used to compare categorical variables and t-test for continuous variables. Multivariate regression was used to compare outcomes of interest between groups. A total of 167,054 patients were analyzed with 97.3% undergoing TKA. TKA patients had a greater overall complication rate than those undergoing UKA (p < 0.001). Readmission rates were approximately 1.5 times higher in TKA compared with UKA (p = 0.002), while no statistically significant difference was discovered in reoperation rates (p = 0.868). TKA was also associated with decreased rates of same day discharge, discharge within 24 hours of surgery, and discharge home (p < 0.001, <0.001, and <0.001, respectively). This study found an increase in complication rates, readmission rates, and LOS, along with a lower likelihood of discharge home when undergoing a TKA. These findings suggest that patients with significant medical comorbidities at baseline may benefit from UKA over TKA when anatomically indicated.

Does a Preoperative Mental Health Diagnosis Affect Pain Management in Patients With Adolescent Idiopathic Scoliosis Undergoing Surgery?

BACKGROUND: Patients with adolescent idiopathic scoliosis (AIS) are typically treated surgically with posterior spinal fusion (PSF) when the curve continues to progress beyond 45 to 50 degrees. In adult patients, studies have shown that preoperative psychiatric diagnoses are associated with poorer clinical outcomes after lumbar spine surgery. This study aims to address whether a preoperative mental health disorder affects outcomes in pediatric patients with AIS treated with PSF. METHODS: We conducted a retrospective study of pediatric patients with a history of AIS requiring operative treatment with PSF at a single center with a minimum of 2-year follow-up. These patients were split into 2 groups: a subset that had a mental health disorder (MHD), and a control group. The MHD subset included patients with anxiety disorder, major depressive disorder, bipolar disorder, manic disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, and stress disorder. The 2 groups were compared using independent student t -test and χ 2 analysis. RESULTS: A total of 417 patients were included in the study. Ninety-three patients were included in the MHD group, and 324 patients were included in the control group. The mean pain score for the MHD group was greater (3.93) compared with the control group (3.34). The PCA demands during inpatient stay for the MHD group were also greater (236.7) compared with the control group (140.0). There was no significant difference in the length of stay in the hospital between the MHD group (4.7 days) and the control group (4.6 days). There was a greater number of patients in the MHD cohort (25.8%) still using narcotic pain medication at first follow-up compared with the control group (12.0%). CONCLUSION: This study suggests that patients with AIS with a preoperative mental health disorder undergoing PSF experience more pain after surgery and require more pain medication during their recovery. LEVEL OF EVIDENCE: III. This is a retrospective review of pediatric patients with adolescent idiopathic scoliosis and a preoperative mental health diagnosis and their pain management requirements during the recovery period from posterior spinal fusion.

Keratoconus in India: Clinical presentation and demographic distribution based on big data analytics.

PURPOSE: This paper aims to describe the clinical presentation and demographic distribution of keratoconus (KCN) in India by analyzing the electronic medical records (EMR) of patients presenting at a multitier ophthalmology hospital network. METHODS: This cross-sectional hospital-based study included the data of 2,384,523 patients presenting between January 2012 and March 2020. Data were collected from an EMR system. Patients with a clinical diagnosis of KCN in at least one eye were included in this study. Univariate analysis was performed to identify the prevalence of KCN. A multiple logistic regression analysis was performed using R software (version 3.5.1), and the odds ratios are reported. RESULTS: Data were obtained for 14,749 (0.62%) patients with 27,703 eyes diagnosed with KCN and used for the analysis. The median age of the patients was 22 (inter-quartile range (IQR): 17-27). In total, 76.64% of adults (odds ratio = 8.77; P = <0.001) were affected the most. The majority of patients were male (61.25%), and bilateral (87.83%) affliction was the most common presentation. A significant proportion of the patients were students (63.98%). Most eyes had mild or no visual impairment (<20/70; 61.42%). Corneal signs included ectasia (41.35%), Fleischer ring (44.52%), prominent corneal nerves (45.75%), corneal scarring (13.60%), Vogts striae (18.97%), and hydrops (0.71%). Only 7.85% showed an association with allergic conjunctivitis. A contact lens clinic assessment was administered to 47.87% of patients. Overall, 10.23% of the eyes affected with KCN underwent a surgical procedure. the most common surgery was collagen cross-linking (8.05%), followed by deep anterior lamellar keratoplasty (1.13%) and penetrating keratoplasty (0.88%). CONCLUSION: KCN is usually bilateral and predominantly affects males. It commonly presents in the second and third decade of life, and only a tenth of the affected eyes require surgical treatment.