Development of highly multiplex targeted proteomics assays in biofluids using the Stellar mass spectrometer.

The development of targeted assays that monitor biomedically relevant proteins is an important step in bridging discovery experiments to large scale clinical studies. Targeted assays are currently unable to scale to hundreds or thousands of targets. We demonstrate the generation of large-scale assays using a novel hybrid nominal mass instrument. The scale of these assays is achievable with the Stellar TM mass spectrometer through the accommodation of shifting retention times by real-time alignment, while being sensitive and fast enough to handle many concurrent targets. Assays were constructed using precursor information from gas-phase fractionated (GPF) data-independent acquisition (DIA). We demonstrate the ability to schedule methods from an orbitrap and linear ion trap acquired GPF DIA library and compare the quantification of a matrix-matched calibration curve from orbitrap DIA and linear ion trap parallel reaction monitoring (PRM). Two applications of these proposed workflows are shown with a cerebrospinal fluid (CSF) neurodegenerative disease protein PRM assay and with a Mag-Net enriched plasma extracellular vesicle (EV) protein survey PRM assay.

Unsuspected Positive Intraoperative Cultures in Aseptic Revision Knee Arthroplasty: Prevalence, Management, and Infection-Free Survivorship.

BACKGROUND: The purpose of this study was to evaluate the management and outcomes of aseptic revision total knee arthroplasty (arTKA) with unsuspected positive cultures (UPCs) compared to those with sterile cultures. METHODS: The institutional database at a single tertiary center was retrospectively reviewed for arTKA from January 2013 to October 2023. Patients who met Musculoskeletal Infection Society (MSIS) criteria for periprosthetic infection (PJI) based on available preoperative infectious workup, received antibiotic spacers, or did not have at least 1 year of follow-up were excluded. Patients were stratified based on intraoperative cultures into 4 cohorts: sterile cultures, 1 UPC, ≥ 2 UPCs with different organisms, and ≥ 2 UPCs with the same organism. Univariable analyses were used to compare these groups. Kaplan-Meyer survivorship analysis assessed infection-free survival at 5 years, and Cox proportional hazards regressions were used to evaluate factors that influence infection-free survival. A total of 691 arTKAs at a mean follow-up of 4.2 years were included in the study. Of these, 49 (7.1%) had 1 UPC with a new organism, 10 (1.4%) had ≥ 2 UPCs of the same organism, and 2 (0.2%) had ≥ 2 UPCs with different organisms. RESULTS: Postoperative antibiotics were prescribed to 114 (16.5%) patients - 13 (26.5%) with 1 UPC, 6 (60.0%) with ≥ 2 UPCs of the same organism, and 0 (0.0%) of patients who had ≥ 2 UPCs of different organisms. There were no differences in infection-free survival at 5 years between patients who had sterile cultures and 1 UPC (96 versus 89%; P = 0.39) nor between sterile cultures and ≥ 2 UPCs of different organisms (96 versus 100%; P < 0.72). However, patients who had ≥ 2 UPCs of the same organism had significantly worse infection-free survival at 5 years compared to patients who had sterile cultures (58 versus 96%; P < 0.001). Cox proportional hazards regression suggested that when adjusting for covariates, an American Society of Anesthesiologists classification of ≥ 3 (hazard ratio [HR] = 3.1; P = 0.007), ≥ 2 UPCs of the same organism (HR = 11.0; P < 0.001), 1 UPC (HR = 4.2; P = 0.018), and arTKA with hinge constructs (HR = 4.1; P = 0.008) were associated with increased risk of re-revision for PJI. CONCLUSION: Patients who had 1 UPC or ≥ 2 UPCs with different organisms had similar infection-free survival at 5 years as patients who had sterile cultures. However, patients who had ≥ 2 UPCs of the same organism had significantly worse infection-free survival at five years. Overall, 1 UPC or ≥ 2 UPCs of the same organism at the time of arTKA may suggest the patient is at higher risk of re-revision for PJI. More studies are needed to determine what interventions can be implemented to mitigate this risk.

Mag-Net: Rapid enrichment of membrane-bound particles enables high coverage quantitative analysis of the plasma proteome.

Membrane-bound particles in plasma are composed of exosomes, microvesicles, and apoptotic bodies and represent ~1-2% of the total protein composition. Proteomic interrogation of this subset of plasma proteins augments the representation of tissue-specific proteins, representing a "liquid biopsy," while enabling the detection of proteins that would otherwise be beyond the dynamic range of liquid chromatography-tandem mass spectrometry of unfractionated plasma. We have developed an enrichment strategy (Mag-Net) using hyper-porous strong-anion exchange magnetic microparticles to sieve membrane-bound particles from plasma. The Mag-Net method is robust, reproducible, inexpensive, and requires <100 µL plasma input. Coupled to a quantitative data-independent mass spectrometry analytical strategy, we demonstrate that we can collect results for >37,000 peptides from >4,000 plasma proteins with high precision. Using this analytical pipeline on a small cohort of patients with neurodegenerative disease and healthy age-matched controls, we discovered 204 proteins that differentiate (q-value < 0.05) patients with Alzheimer's disease dementia (ADD) from those without ADD. Our method also discovered 310 proteins that were different between Parkinson's disease and those with either ADD or healthy cognitively normal individuals. Using machine learning we were able to distinguish between ADD and not ADD with a mean ROC AUC = 0.98 ± 0.06.

Subsequent total joint arthroplasty: Are we learning from the first stage?

BACKGROUND: With the increasing incidence of total joint arthroplasty (TJA), there is a desire to reduce peri-operative complications and resource utilization. As degenerative conditions progress in multiple joints, many patients undergo multiple procedures. AIM: To determine if both physicians and patients learn from the patient's initial arthroplasty, resulting in improved outcomes following the second procedure. METHODS: The institutional database was retrospectively queried for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients with only unilateral THA or TKA, and patients undergoing same-day bilateral TJA, were excluded. Patient demographics, comorbidities, and implant sizes were collected at the time of each procedure and patients were stratified by first vs second surgery. Outcome metrics evaluated included operative time, length of stay (LOS), disposition, 90-d readmissions and emergency department (ED) visits. RESULTS: A total of 642 patients, including 364 undergoing staged bilateral TKA and 278 undergoing bilateral THA, were analyzed. There was no significant difference in demographics or comorbidities between the first and second procedure, which were separated by a mean of 285 d. For THA and TKA, LOS was significantly less for the second surgery, with 66% of patients having a shorter hospitalization (P < 0.001). THA patients had significantly decreased operative time only when the same sized implant was utilized (P = 0.025). The vast majority (93.3%) of patients were discharged to the same type of location following their second surgery. However, when a change in disposition was present from the first surgery, patients were significantly more likely to be discharged to home after the second procedure (P = 0.033). There was no difference between procedures for post-operative readmissions (P = 0.438) or ED visits (P = 0.915). CONCLUSION: After gaining valuable experience recovering from the initial surgery, a patient's perioperative outcomes are improved for their second TJA. This may be the result of increased confidence and decreased anxiety, and it supports the theory that enhanced patient education pre-operatively may improve outcomes. For the surgical team, the second procedure of a staged THA is more efficient, although this finding did not hold for TKA.

Total Joint Arthroplasty Is a Viable Treatment Option for Patients With Osteonecrosis and Osteoarthritis After Bone Marrow Transplantation.

Background: Long-term survival in patients who receive bone marrow transplantation (BMT) is increasing. However, osteonecrosis and secondary osteoarthritis (OA) of the hip and knee are common complications in this population due to post-transplant steroid treatment to prevent graft vs host disease. The purpose of this study was to evaluate the outcomes of total joint arthroplasty (TJA) in patients with prior BMT and compare them to those of patients undergoing TJA for primary OA. Methods: Patients with a history of BMT undergoing primary TJA from 2013 to 2021 were retrospectively reviewed. Patients were matched 1:1 by surgical site, sex, age, body mass index, American Society of Anesthesiologists score, and Elixhauser Comorbidity Index to patients undergoing TJA for primary OA. Demographics, intraoperative blood loss, perioperative transfusion requirements, hospital length of stay, 90-day emergency department visits and readmissions, all-cause revisions, and 2-year mortality were compared between cohorts. Results: There were 17 patients undergoing total knee arthroplasty (TKA) after BMT (TKA-BMT) and 43 patients undergoing total hip arthroplasty (THA) after BMT (THA-BMT). More TKA-BMT and THA-BMT patients were immunosuppressed preoperatively compared to 17 matched TKA-OA and 43 THA-OA patients (P = .018 and P < .001). There were no other significant perioperative differences between BMT and OA groups. Two-year patient and implant survivorship for TKA-BMT and THA-BMT patients were high and not statistically different from TKA-OA and THA-OA cohorts. Conclusions: TJA after BMT provides satisfactory perioperative and short-term outcomes and is a viable treatment option for patients with osteonecrosis and secondary OA after BMT treatment.

A framework for quality control in quantitative proteomics.

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow from planning to analysis. We share real-world case studies applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at protein and peptide-level allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis using Skyline, longitudinal QC metrics using AutoQC, and server-based data deposition using PanoramaWeb. We propose that this integrated approach to QC be used as a starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible.

Hepatitis B virus e antigen induces atypical metabolism and differentially regulates programmed cell deaths of macrophages.

Macrophages can undergo M1-like proinflammatory polarization with low oxidative phosphorylation (OXPHOS) and high glycolytic activities or M2-like anti-inflammatory polarization with the opposite metabolic activities. Here we show that M1-like macrophages induced by hepatitis B virus (HBV) display high OXPHOS and low glycolytic activities. This atypical metabolism induced by HBV attenuates the antiviral response of M1-like macrophages and is mediated by HBV e antigen (HBeAg), which induces death receptor 5 (DR5) via toll-like receptor 4 (TLR4) to induce death-associated protein 3 (DAP3). DAP3 then induces the expression of mitochondrial genes to promote OXPHOS. HBeAg also enhances the expression of glutaminases and increases the level of glutamate, which is converted to α-ketoglutarate, an important metabolic intermediate of the tricarboxylic acid cycle, to promote OXPHOS. The induction of DR5 by HBeAg leads to apoptosis of M1-like and M2-like macrophages, although HBeAg also induces pyroptosis of the former. These findings reveal novel activities of HBeAg, which can reprogram mitochondrial metabolism and trigger different programmed cell death responses of macrophages depending on their phenotypes to promote HBV persistence.

Patient Perceptions and Interest in Robotic-Assisted Total Joint Arthroplasty.

Background: Robotic-assisted total joint arthroplasty (rTJA) has growing interest among patients and surgeons. However, patient interest in and perceptions of rTJA have not been well explored. We sought to investigate the influence of patient demographics on interest in rTJA and patient perceptions regarding rTJA. Methods: Patients presenting for their initial adult reconstruction consultation received an optional anonymous survey prior to seeing the provider. Patient sociodemographic parameters were recorded. Additional questions assessed interest in and perceptions surrounding rTJA. Results were analyzed to determine whether patient factors correlated with survey responses. Results: A total of 360 patients participated. Analysis of responses revealed 77.8% of patients were interested in rTJA. Interest level positively correlated with patient age (Rs = 0.139, P = .010), education level (Rs = 0.168, P = .002), household income (Rs = 0.274, P < .001), and White race (F = 4.157, P = .016). At least 100 patients believed rTJA was easier and more accurate, but more expensive and had a significant learning curve for the surgeon. Over 100 patients believed robots were capable of independently performing most or all of the rTJA operation. Conclusions: Patient interest in rTJA varies between patients. Many patients have an incomplete understanding of rTJA, and orthopaedic surgeons should address patient perceptions during surgical consultation. Level of Evidence: IV, Cross-sectional study.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Inertial Sensor Gait Analysis of Trendelenburg Gait in Patients Who Have Hip Osteoarthritis.

BACKGROUND: Gait abnormalities such as Trendelenburg gait (TG) in patients who have hip osteoarthritis (OA) have traditionally been evaluated using clinicians' visual assessment. Recent advances in portable inertial gait sensors offer more sensitive, quantitative methods for gait assessment in clinical settings. This study sought to compare sensor-derived metrics in a cohort of hip OA patients when stratified by clinical TG severity. METHODS: There were 42 patients who had hip OA and were grouped by TG severity (mild, moderate, and severe) through visual assessment by a single arthroplasty surgeon who had > 30 years of experience. After informed consent, wireless inertial sensors placed at the midpoint of the intercristal line collected gait parameters including pelvic shift, support time, toe-off symmetry, impact, and cadence. Clinical data on hip strength, range of motion, and Kellgren-Lawrence grade were collected. RESULTS: Worsening TG severity had a higher mean Kellgren-Lawrence grade (2.5 versus 3.2 versus 3.4; P = .014) and reduced passive hip abduction (P = .004). Severe TG group demonstrated predominantly contralateral pelvic shift (n = 9 of 10, 90.0%), while ipsilateral shift was more frequently detected in moderate (n = 10 of 18, 55.6%) and mild groups (n = 9 of 14, 64.3%; P = .021). Contralateral single support time bias was greatest in severe TG (35.7% versus 50.0 versus 90.0%; P = .027). Asymmetric toe-off, impact, and support times were observed in all groups. CONCLUSIONS: Traditional understanding of TG is that truncal shift occurs to the ipsilateral side. Using sensor-based measurements, the present study demonstrates a shift of the weight-bearing axis toward the contralateral side with increasing TG severity, which has not been previously described. Inertial sensors are feasible, quantitative gait measuring tools, and may reveal subtle patterns not readily discernible by traditional methods.

Gender Trends in Authorship in 6 Major Orthopaedic Journals.

BACKGROUND: Historically, orthopaedic surgery has had low female representation, with <6% of practicing surgeons identifying as female. Although prior literature has illustrated gender disparities in first and last authorship as well as changes in gender representation over time, less attention has been paid to middle authorship. We hypothesized that trends in female authorship would reflect increasing female participation in orthopaedic surgery and orthopaedic subspecialties coinciding with an overall increase in female authorship. METHODS: Bibliometric information from articles published between 2011 and 2021 in 6 orthopaedic journals was extracted with use of the Web of Science. Collected data included author order, author names, affiliation, and corresponding author address. A gender was assigned with the use of Genderize.io, which is validated software, on the basis of author first name. Statistical analysis was performed with use of an analysis of variance for each journal, and linear regression was performed to determine trends, controlling for year. RESULTS: Among all included orthopaedic journals, female middle authorship increased by 5 percentage points, female first authorship increased by 4 percentage points, and female last authorship increased by 1 percentage point. Over the study period, the highest rate of female middle authorship (28%) was seen in the Journal of Pediatric Orthopaedics, whereas the lowest rate (16%) was seen in The Journal of Arthroplasty . We found that the 5 highest-producing female last authors were, on average, cited significantly less per publication than their male counterparts in all but 2 journals. CONCLUSIONS: Gender gaps exist within orthopaedic surgery as well as within its body of literature. Although this study highlights areas of growth, it also promotes further inquiry into research productivity and the availability of opportunity within orthopaedic surgery as a whole. The increase in female middle authorship overall and in each journal demonstrates momentum for future growth for women in the field of orthopaedic surgery.

Family-based and external discrimination experienced by multiracial individuals: Links to internalizing symptoms and familial support.

Multiracial individuals are exposed to many forms of interpersonal racial discrimination, including general discrimination against their monoracial groups and discrimination against being multiracial. Because their families include members of different racial groups, multiracial people may also be exposed to various forms of discrimination from within the family. In the present study, we leverage recent advances in latent profile analysis to identify distinct patterns of family-based and external (i.e., from outside the family unit) discrimination experienced by multiracial college students, the differential impacts of these discrimination patterns on depressive and anxiety symptoms, and whether parental support of participants' multiracial experiences and identity impacts their exposure to different forms of discrimination. In a sample of 635 diverse multiracial college students (Mage = 21.2, SD = 5.3, range = 18-57, 74.0% female) from three U.S. universities, we identified three distinct discrimination profiles: High External and Familial Discrimination (43.2%), Average External Low Familial Discrimination (32.1%), and Low External and Familial Discrimination (24.7%). Profiles differed in depressive and anxiety symptomatology, with those in the High External and Familial Discrimination profile displaying the worst outcomes. Parental support of multiracial experiences was associated with lower levels of family-based discrimination. The complex relations between parental support, family-based discrimination, and multiracial participants' internalizing symptomology are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Machine learning enabled multiplex detection of periodontal pathogens by surface-enhanced Raman spectroscopy.

Periodontitis is a chronic inflammation of the periodontium caused by a persistent bacterial infection, resulting in destruction of the supporting structures of teeth. Analysis of microbial composition in saliva can inform periodontal status. Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Streptococcus mutans (Sm) are among reported periodontal pathogens, and were used as model systems in this study. Our atomic force microscopic (AFM) study revealed that these pathogens are biological nanorods with dimensions of 0.6-1.1 µm in length and 500-700 nm in width. Current bacterial detection methods often involve complex preparation steps and require labeled reporting motifs. Employing surface-enhanced Raman spectroscopy (SERS), we revealed cell-type specific Raman signatures of these pathogens for label-free detection. It overcame the complexity associated with spectral overlaps among different bacterial species, relying on high signal-to-noise ratio (SNR) spectra carefully collected from pure species samples. To enable simple, rapid, and multiplexed detection, we harnessed advanced machine learning techniques to establish predictive models based on a large set of raw spectra of each bacterial species and their mixtures. Using these models, given a raw spectrum collected from a bacterial suspension, simultaneous identification of all three species in the test sample was achieved at 95.6 % accuracy. This sensing modality can be applied to multiplex detection of a broader range and a larger set of periodontal pathogens, paving the way for hassle-free detection of oral bacteria in saliva with little to no sample preparation.

Long 3'UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation.

Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded RNA (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report that human neurons intrinsically carry exceptionally high levels of immunostimulatory dsRNAs and identify long 3'UTRs as giving rise to neuronal dsRNA structures. We found that the neuron-enriched ELAVL family of genes (ELAVL2, ELAVL3, and ELAVL4) can increase (i) 3'UTR length, (ii) dsRNA load, and (iii) activation of dsRNA-sensing PRRs such as MDA5, PKR, and TLR3. In wild-type neurons, neuronal dsRNAs signaled through PRRs to induce tonic production of the antiviral type I interferon. Depleting ELAVL2 in WT neurons led to global shortening of 3'UTR length, reduced immunostimulatory dsRNA levels, and rendered WT neurons susceptible to herpes simplex virus and Zika virus infection. Neurons deficient in ADAR1, a dsRNA-editing enzyme mutated in the neuroinflammatory disorder Aicardi-Goutières syndrome, exhibited intolerably high levels of dsRNA that triggered PRR-mediated toxic inflammation and neuronal death. Depleting ELAVL2 in ADAR1 knockout neurons led to prolonged neuron survival by reducing immunostimulatory dsRNA levels. In summary, neurons are specialized cells where PRRs constantly sense "self" dsRNAs to preemptively induce protective antiviral immunity, but maintaining RNA homeostasis is paramount to prevent pathological neuroinflammation.

Evaluating the Performance of the Astral Mass Analyzer for Quantitative Proteomics Using Data-Independent Acquisition.

We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data-independent acquisition, the Thermo Scientific Orbitrap Astral mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific Orbitrap mass spectrometers, which have long been the gold standard for high-resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high-quality quantitative measurements across a wide dynamic range. We also use a newly developed extracellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5000 plasma proteins in a 60 min gradient with the Orbitrap Astral mass spectrometer.

Dynamic Data-Independent Acquisition Mass Spectrometry with Real-Time Retrospective Alignment.

Data-independent acquisition (DIA) mass spectrometry has grown in popularity in recent years, because of the reproducibility and quantitative rigor of a systematic tandem mass spectrometry (MS/MS) sampling method. However, traditional DIA methods may spend valuable instrument time acquiring MS/MS spectra with no usable information in them, affecting sensitivity and quantitative performance. We developed a DIA strategy that dynamically adjusts the MS/MS windows during the chromatographic separation. The method focuses MS/MS acquisition on the most relevant mass range at each point in time─increasing the quantitative sensitivity by increasing the time spent on each DIA window. We demonstrate an improved lower limit of quantification, on average, without sacrificing the number of peptides detected.

Evaluating the Performance of the Astral Mass Analyzer for Quantitative Proteomics Using Data Independent Acquisition.

We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data independent acquisition, the Thermo Scientific™ Orbitrap™ Astral™ mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific™ Orbitrap™ mass spectrometers, which have long been the gold standard for high resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high quality quantitative measurements across a wide dynamic range. We also use a newly developed extra-cellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5,000 plasma proteins in a 60-minute gradient with the Orbitrap Astral mass spectrometer.

Early surgery for perforated appendicitis: Are we moving the needle on postoperative abscess?

BACKGROUND: Perforated appendicitis is often managed nonoperatively though upfront surgery is becoming more common. We describe postoperative outcomes for patients undergoing surgery at their index hospitalization for perforated appendicitis. METHODS: We used the 2016-2020 National Surgical Quality Improvement Program database to identify patients with appendicitis who underwent appendectomy or partial colectomy. The primary outcome was surgical site infection (SSI). RESULTS: 132,443 patients with appendicitis underwent immediate surgery. Of 14.1% patients with perforated appendicitis, 84.3% underwent laparoscopic appendectomy. Intra-abdominal abscess rates were lowest after laparoscopic appendectomy (9.4%). Open appendectomy (OR 5.14, 95% CI 4.06-6.51) and laparoscopic partial colectomy (OR 4.60, 95% CI 2.38-8.89) were associated with higher likelihoods of SSIs. CONCLUSIONS: Upfront surgical management of perforated appendicitis is now predominantly approached by laparoscopy, often without bowel resection. Postoperative complications occurred less frequently with laparoscopic appendectomy compared to other approaches. Laparoscopic appendectomy during the index hospitalization is an effective approach to perforated appendicitis.