Stereodivergent Synthesis of 1,4-Dicarbonyl Compounds through Sulfonium Rearrangement: Mechanistic Investigation, Stereocontrolled Access to γ-Lactones and γ-Lactams, and Total Synthesis of Paraconic Acids.

Although simple γ-lactones and γ-lactams have received considerable attention from the synthetic community, particularly due to their relevance in biological and medicinal contexts, stereoselective synthetic approaches to more densely substituted derivatives remain scarce. The in-depth study presented herein, showcasing a straightforward method for the stereocontrolled synthesis of γ-lactones and γ-lactams, builds on and considerably expands the stereodivergent synthesis of 1,4-dicarbonyl compounds by a ynamide/vinyl sulfoxide coupling. A full mechanistic and computational study of the rearrangement was conducted, uncovering the role of all of the reaction components and providing a rationale for stereoselection. The broad applicability of the developed tools to streamlining synthesis is demonstrated by concise enantioselective total syntheses of (+)-nephrosteranic acid, (+)-rocellaric acid, and (+)-nephromopsinic acid.

Use of half red blood cell units in oncology patients during severe shortages to extend hospital supply.

BACKGROUND: The COVID-19 pandemic exerted an unprecedented impact on the blood supply from 2020 through 2022. As a result, throughout 2021 there were months our hospital had less than one-day supply of type O RBCs. To meet transfusion needs, whole RBC units were split into half units and issued to stable, non-bleeding patients. This single-institution, retrospective study examines time intervals to subsequent transfusion and total numbers of RBC units subsequently transfused after the first half or whole RBC unit. STUDY DESIGN AND METHODS: Patients who were transfused RBC between May 21, 2021 and November 1, 2021 were divided into in- and outpatient groups, then based on whether they received at least 1 half RBC unit or only whole RBC units during the study period. The time interval between this first half unit transfusion, or first whole unit transfusion in those who did not receive half units, and the subsequent RBC transfusion within 90 days was calculated and compared, as well as the total number of RBC units transfused 30 days after the first unit. RESULTS: In general, patients transfused with half units received a subsequent transfusion significantly earlier than those transfused with whole units. Additionally, receiving an index half unit was associated with more RBC transfusions in the following 30 days (p = .001). CONCLUSION: Transfusion of half RBC units during a severe RBC blood shortage can temporarily decrease RBC usage but will result in a shorter interval to the next transfusion and greater total number of RBC units transfused in subsequent days.

How Strong Is the Ligamentum Teres of the Hip? A Biomechanical Analysis.

BACKGROUND: Intraarticular hip pain represents a substantial clinical challenge, with recent studies implicating lesions in the ligamentum teres as potential contributors. Even more so, damage to the ligamentum teres is particularly prevalent among young patients undergoing joint-preserving interventions. Although several studies have investigated the biomechanical attributes of the ligamentum teres, inconsistencies in reported findings and reliance on cadaveric or animal models have raised concerns regarding the extrapolation of results to clinical practice. Furthermore, there is a lack of research examining ligamentum teres biomechanics specifically within the relevant patient cohort-individuals who benefit from joint-preserving surgical interventions. QUESTIONS/PURPOSES: We sought (1) to determine the biomechanical properties (ultimate load to failure, tensile strength, stiffness, and elastic modulus) of fresh-frozen ligaments from patients undergoing surgical hip dislocation, and (2) to identify patient-specific factors that are associated with them. METHODS: This was an institutional review board-approved study on intraoperatively harvested ligamentum teres from 74 consecutive patients undergoing surgical hip dislocation for joint preservation (August 2021 to September 2022). After the exclusion of patients with previous surgery, posttraumatic deformities, avascular necrosis, slipped capital femoral epiphysis, and Perthes disease, 31 ligaments from 31 patients were analyzed. The mean age of the study group was 27 ± 8 years, and 61% (19) of participants were male. The main indication for surgery was femoroacetabular impingement. Standardized AP pelvic and axial radiographs and CT scans were performed in all patients for better radiological description of the population and to identify associated radiological factors. The ligament was thoroughly transected at its origin on the fossa acetabuli and at the insertion area on the fovea capitis and stored at -20°C until utilization. Specimens were mounted to a materials testing machine via custom clamps that minimized slippage and the likelihood of failure at the clamp. Force-displacement and stress-strain curves were generated. Ultimate failure load (N), tensile strength (MPa), stiffness (N/mm), and elastic modulus (MPa) were determined. Using a multivariate regression analysis and a subgroup analysis, we tested demographic, degenerative, and radiographic factors as potential associated factors. RESULTS: The ligamentum teres demonstrated an ultimate load to failure of 126 ± 92 N, and the tensile strength was 1 ± 1 MPa. The ligaments exhibited a stiffness of 24 ± 15 N/mm and an elastic modulus of 7 ± 5 MPa. After controlling for potential confounding variables like age, fossa/fovea degeneration, and acetabular/femoral morphologies, we found that female sex was an independent factor for higher tensile strength, stiffness, and elastic modulus. Excessive femoral version was independently associated with lower load to failure (HR 122 [95% CI 47 to 197]) and stiffness (HR 15 [95% CI 2 to 27]). Damage to the acetabular fossa was associated with reduced load to failure (HR -93 [95% CI -159 to -27]). CONCLUSION: Overall, the ligamentum teres is a relatively weak ligament. Sex, degeneration, and excessive femoral version are influencing factors on strength of the ligamentum teres. The ligamentum teres exhibits lower strength compared with other joint-stabilizing ligaments, which calls into question its overall contribution to hip stability. CLINICAL RELEVANCE: Young patients undergoing hip-preserving surgery are the population at risk for ligamentum teres lesions. Baseline values for load to failure, tensile strength, elastic modulus, and stiffness are needed to better understand those lesions in this cohort of interest.

Unicortical Button Fixation Provide Higher Strength Compared with Transosseous Repair for Subscapularis Tendon in Total Shoulder Arthroplasty.

BACKGROUND: Subscapularis tendon (SSc) dysfunction following total shoulder arthroplasty (TSA) results in poor functional outcomes. There have been numerous SSc repair constructs tested biomechanically and clinically, however, none has been demonstrated as superior. Newer techniques and implants have emerged, but have not been fully tested. HYPOTHESIS: We hypothesized that the unicortical button (UB) fixation will provide significantly improved restoration of the anatomic footprint and biomechanical properties when compared to transosseous (TO) repair of the SSc. METHODS: A digital footprint of SSc humeral insertion was obtained in 6 pairs of fresh-frozen cadaveric shoulders using a three-dimensional (3-D) digitizer. A complete SSc tear was created, and each pair of shoulders was randomized to either SSc repair with UB or TO repair. Each specimen underwent a cyclic loading protocol followed by pull-to-failure. The failure load, elongation at failure, gapping failure, number of cycles until failure, the load at key gapping points (1 mm, 3 mm, 5 mm, and 10 mm) and the failure mode were recorded using high-resolution video recording. 3-D surfaces of the insertion footprint and repair site were obtained, and surface areas were calculated using a custom MATLAB script and laser scanner. Paired t-tests were conducted to compare differences between two repair groups. RESULTS: Failure load was significantly higher in the UB group (382.4 N ± 56.5 N) than in the TO group (253.6 N ± 103.4 N, p=0.005). TO repair provided higher gapping at failure (28.8 mm ± 8.2 mm) than UB repair (10.4 mm ± 6.8 mm, p=0.0017). UB repair had significantly higher load at the 1-mm, 5-mm, and 10-mm gapping compared with TO repair with p=0.042, p=0.033, and p=0.0076, respectively. There were no significant differences between elongation failure, the difference in footprint area from native to repair states, or the percentage of restored footprint area between groups. (p=0.26, p=0.18 and p=0.21 respectively) CONCLUSION: The UB fixation showed a significantly lower gap at failure, higher failure load and number of cycles until failure, and higher gap loads compared with the traditional TO repair for SSc. Although more clinical research is necessary, the UB fixation that utilizes cortical bone presents promising results.

Divine Control Beliefs, Health Locus of Control, and Subjective Life Expectancy in the United States.

Little evidence has considered the extent to which feelings of health-related control may arise from religious beliefs to influence survival expectations. Moreover, research on the linkages between religion and sense of control has yielded mixed results. Using CHAPS (2021) data, this study examines whether divine control beliefs predict subjective life expectancy (SLE), and whether this link is mediated by an individual's health locus of control (HLC). Findings support a mediational model and show that individuals who place more dependence on God report a greater sense of control over their health, which in turn results in greater longevity expectations. Our findings offer insight into the mechanisms that underlie the association between divine control beliefs and SLE and add to the body of literature documenting religion's salutary role in promoting both a sense of empowerment and greater survival expectations.

eNAMPT Is a Novel Damage-associated Molecular Pattern Protein That Contributes to the Severity of Radiation-induced Lung Fibrosis.

The paucity of therapeutic strategies to reduce the severity of radiation-induced lung fibrosis (RILF), a life-threatening complication of intended or accidental ionizing radiation exposure, is a serious unmet need. We evaluated the contribution of eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a damage-associated molecular pattern (DAMP) protein and TLR4 (Toll-like receptor 4) ligand, to the severity of whole-thorax lung irradiation (WTLI)-induced RILF. Wild-type (WT) and Nampt+/- heterozygous C57BL6 mice and nonhuman primates (NHPs, Macaca mulatta) were exposed to a single WTLI dose (9.8 or 10.7 Gy for NHPs, 20 Gy for mice). WT mice received IgG1 (control) or an eNAMPT-neutralizing polyclonal or monoclonal antibody (mAb) intraperitoneally 4 hours after WTLI and weekly thereafter. At 8-12 weeks after WTLI, NAMPT expression was assessed by immunohistochemistry, biochemistry, and plasma biomarker studies. RILF severity was determined by BAL protein/cells, hematoxylin and eosin, and trichrome blue staining and soluble collagen assays. RNA sequencing and bioinformatic analyses identified differentially expressed lung tissue genes/pathways. NAMPT lung tissue expression was increased in both WTLI-exposed WT mice and NHPs. Nampt+/- mice and eNAMPT polyclonal antibody/mAb-treated mice exhibited significantly attenuated WTLI-mediated lung fibrosis with reduced: 1) NAMPT and trichrome blue staining; 2) dysregulated lung tissue expression of smooth muscle actin, p-SMAD2/p-SMAD1/5/9, TGF-ß, TSP1 (thrombospondin-1), NOX4, IL-1ß, and NRF2; 3) plasma eNAMPT and IL-1ß concentrations; and 4) soluble collagen. Multiple WTLI-induced dysregulated differentially expressed lung tissue genes/pathways with known tissue fibrosis involvement were each rectified in mice receiving eNAMPT mAbs.The eNAMPT/TLR4 inflammatory network is essentially involved in radiation pathobiology, with eNAMPT neutralization an effective therapeutic strategy to reduce RILF severity.

Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody.

RATIONALE: The severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 pandemic has highlighted the serious unmet need for effective therapies that reduce acute respiratory distress syndrome (ARDS) mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor (TLR)4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target. METHODS: Wild-type C57BL/6J or endothelial cell (EC)-cNAMPT -/- knockout mice (targeted EC NAMPT deletion) were exposed to either a lipopolysaccharide (LPS)-induced ("one-hit") or a combined LPS/ventilator ("two-hit")-induced acute inflammatory lung injury model. A NAMPT-specific monoclonal antibody (mAb) imaging probe (99mTc-ProNamptor) was used to detect NAMPT expression in lung tissues. Either an eNAMPT-neutralising goat polyclonal antibody (pAb) or a humanised monoclonal antibody (ALT-100 mAb) were used in vitro and in vivo. RESULTS: Immunohistochemical, biochemical and imaging studies validated time-dependent increases in NAMPT lung tissue expression in both pre-clinical ARDS models. Intravenous delivery of either eNAMPT-neutralising pAb or mAb significantly attenuated inflammatory lung injury (haematoxylin and eosin staining, bronchoalveolar lavage (BAL) protein, BAL polymorphonuclear cells, plasma interleukin-6) in both pre-clinical models. In vitro human lung EC studies demonstrated eNAMPT-neutralising antibodies (pAb, mAb) to strongly abrogate eNAMPT-induced TLR4 pathway activation and EC barrier disruption. In vivo studies in wild-type and EC-cNAMPT -/- mice confirmed a highly significant contribution of EC-derived NAMPT to the severity of inflammatory lung injury in both pre-clinical ARDS models. CONCLUSIONS: These findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker and NAMPT genotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine.

VE-cadherin signaling induces EB3 phosphorylation to suppress microtubule growth and assemble adherens junctions.

Vascular endothelial (VE)-cadherin homophilic adhesion controls endothelial barrier permeability through assembly of adherens junctions (AJs). We observed that loss of VE-cadherin-mediated adhesion induced the activation of Src and phospholipase C (PLC)γ2, which mediated Ca(2+) release from endoplasmic reticulum (ER) stores, resulting in activation of calcineurin (CaN), a Ca(2+)-dependent phosphatase. Downregulation of CaN activity induced phosphorylation of serine 162 in end binding (EB) protein 3. This phospho-switch was required to destabilize the EB3 dimer, suppress microtubule (MT) growth, and assemble AJs. The phospho-defective S162A EB3 mutant, in contrast, induced MT growth in confluent endothelial monolayers and disassembled AJs. Thus, VE-cadherin outside-in signaling regulates cytosolic Ca(2+) homeostasis and EB3 phosphorylation, which are required for assembly of AJs. These results identify a pivotal function of VE-cadherin homophilic interaction in modulating endothelial barrier through the tuning of MT dynamics.

Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets.

Mechanical ventilation is a life-saving intervention in critically ill patients with respiratory failure due to acute respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation also creates excessive mechanical stress that directly augments lung injury, a syndrome known as ventilator-induced lung injury (VILI). The pathobiology of VILI and ARDS shares many inflammatory features including increases in lung vascular permeability due to loss of endothelial cell barrier integrity resulting in alveolar flooding. While there have been advances in the understanding of certain elements of VILI and ARDS pathobiology, such as defining the importance of lung inflammatory leukocyte infiltration and highly induced cytokine expression, a deep understanding of the initiating and regulatory pathways involved in these inflammatory responses remains poorly understood. Prevailing evidence indicates that loss of endothelial barrier function plays a primary role in the development of VILI and ARDS. Thus this review will focus on the latest knowledge related to 1) the key role of the endothelium in the pathogenesis of VILI; 2) the transcription factors that relay the effects of excessive mechanical stress in the endothelium; 3) the mechanical stress-induced posttranslational modifications that influence key signaling pathways involved in VILI responses in the endothelium; 4) the genetic and epigenetic regulation of key target genes in the endothelium that are involved in VILI responses; and 5) the need for novel therapeutic strategies for VILI that can preserve endothelial barrier function.

In the pursuit of a semantic similarity metric based on UMLS annotations for articles in PubMed Central Open Access.

MOTIVATION: Although full-text articles are provided by the publishers in electronic formats, it remains a challenge to find related work beyond the title and abstract context. Identifying related articles based on their abstract is indeed a good starting point; this process is straightforward and does not consume as many resources as full-text based similarity would require. However, further analyses may require in-depth understanding of the full content. Two articles with highly related abstracts can be substantially different regarding the full content. How similarity differs when considering title-and-abstract versus full-text and which semantic similarity metric provides better results when dealing with full-text articles are the main issues addressed in this manuscript. METHODS: We have benchmarked three similarity metrics - BM25, PMRA, and Cosine, in order to determine which one performs best when using concept-based annotations on full-text documents. We also evaluated variations in similarity values based on title-and-abstract against those relying on full-text. Our test dataset comprises the Genomics track article collection from the 2005 Text Retrieval Conference. Initially, we used an entity recognition software to semantically annotate titles and abstracts as well as full-text with concepts defined in the Unified Medical Language System (UMLS®). For each article, we created a document profile, i.e., a set of identified concepts, term frequency, and inverse document frequency; we then applied various similarity metrics to those document profiles. We considered correlation, precision, recall, and F1 in order to determine which similarity metric performs best with concept-based annotations. For those full-text articles available in PubMed Central Open Access (PMC-OA), we also performed dispersion analyses in order to understand how similarity varies when considering full-text articles. RESULTS: We have found that the PubMed Related Articles similarity metric is the most suitable for full-text articles annotated with UMLS concepts. For similarity values above 0.8, all metrics exhibited an F1 around 0.2 and a recall around 0.1; BM25 showed the highest precision close to 1; in all cases the concept-based metrics performed better than the word-stem-based one. Our experiments show that similarity values vary when considering only title-and-abstract versus full-text similarity. Therefore, analyses based on full-text become useful when a given research requires going beyond title and abstract, particularly regarding connectivity across articles. AVAILABILITY: Visualization available at ljgarcia.github.io/semsim.benchmark/, data available at http://dx.doi.org/10.5281/zenodo.13323.

BioJS: an open source JavaScript framework for biological data visualization.

SUMMARY: BioJS is an open-source project whose main objective is the visualization of biological data in JavaScript. BioJS provides an easy-to-use consistent framework for bioinformatics application programmers. It follows a community-driven standard specification that includes a collection of components purposely designed to require a very simple configuration and installation. In addition to the programming framework, BioJS provides a centralized repository of components available for reutilization by the bioinformatics community. AVAILABILITY AND IMPLEMENTATION: http://code.google.com/p/biojs/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A Rare Case of Cutaneous Gastric Adenocarcinoma With Signet Ring Cell Features.

Cutaneous metastatic disease from primary gastric cancer is quite scarce, often going unrecognized. In this case, the patient presented with an expanding rash that was biopsied, with findings concerning for metastatic adenocarcinoma from a suspected luminal upper gastrointestinal origin. Subsequent biopsies during an esophagogastroduodenoscopy confirmed poorly differentiated adenocarcinoma with signet ring cell features, most likely from an upper gastrointestinal primary (gastric vs gastroesophageal junction). We review this case to help providers identify signet cell type cutaneous metastases of gastric cancer quickly to improve patient outcomes.

Correction to: A Rare Case of Cutaneous Gastric Adenocarcinoma With Signet Ring Cell Features.

[This corrects the article DOI: 10.14309/crj.0000000000001299.].

Rare Metastasis of Esophageal Adenocarcinoma to the Female Reproductive Tract.

Esophageal cancer is common and typically metastasizes to the liver, lung, and lymph nodes. Reproductive tract metastases are extremely rare. In fact, to the best of our knowledge, only 2 cases of esophageal carcinoma metastasizing to the ovaries have been reported. Thus, increased recognition of unusual metastatic sites is necessary to decrease the morbidity and mortality from distant esophageal metastases. We present a case of ovarian and fallopian tube metastases from esophageal adenocarcinoma in a 59-year-old woman.

The Development of Extensive Subcutaneous Emphysema Following Robotic Total Abdominal Colectomy Due to Lynch Syndrome: A Case Report.

Subcutaneous emphysema, the presence of air in the subcutaneous layer of the skin, is a possible result of surgical, infectious, or spontaneous etiologies. Although usually self-limiting, the development of subcutaneous emphysema in the perioperative period has been associated with delayed extubation and the development of complications such as pneumomediastinum, pneumoperitoneum, and pneumothorax and can worsen clinical outcomes in these patients. Here, we report the case of a 57-year-old male patient who presented to the operating room (OR) for a robotic total colectomy due to Lynch syndrome. The procedure was complicated by the development of diffuse, severe subcutaneous emphysema, which was recognized by palpable crepitus and obscuration of anatomical landmarks during an attempted transversus abdominis plane (TAP) block for pain control prior to patient extubation. The decision was made to leave the patient intubated and managed postoperatively in the ICU, where radiographic and computerized tomography (CT) scans confirmed the severity of subcutaneous emphysema. Hemodynamic and respiratory status were managed in the ICU and on postoperative day 3 the patient passed an endotracheal cuff leak test and was extubated. The patient was transferred to a surgical step-down on postoperative day 7 and following the resolution of ileus and acute kidney injury (AKI), he was discharged from the hospital on postoperative day 17.

Judgment, shame, and coercion: the criminal legal system and reproductive autonomy.

BACKGROUND: A growing body of research has called attention to limitations to reproductive autonomy in both women who are socially disadvantaged and in those who have had contact with the criminal legal (CL) system. However, it is unclear whether CL system contact influences contraceptive use patterns and how these processes unfold. We utilize a mixed-methods approach to investigate whether history of arrest is associated with receipt of contraceptive counseling, use of long-term contraception, sterilization, and subsequent desire for reversal of sterilization. We further consider how agents in and around the CL system may influence women's reproductive decisions and outcomes (856 survey respondents; 10 interviewees). RESULTS: We observe that women who have been arrested more commonly report receipt of contraceptive counseling and sterilization. They are also significantly more likely to want their sterilization reversed. Our in-depth interviews suggest that women with CL contact experience considerable shame, and in some cases, coercion to limit fertility from various agents in and outside the criminal legal system including medical providers, Parole/Probation Officers (POs), guards, and family members. CONCLUSIONS: Our findings suggest the need for ongoing attention to how exposure to this system may promote uneven use of certain forms of contraception and dissatisfaction, i.e., desire for reversal of sterilization, among these women. Findings further suggest that de-emphasizing the CL system as a means through which to address reproductive needs should be considered.

Chronic Steroid Use Does Not Increase the Risk of Superficial Surgical Site Infection or Wound Dehiscence Following Total Ankle Arthroplasty.

Introduction Total ankle arthroplasty (TAA) is an effective treatment for end-stage ankle arthritis. Recent surgical and technological advances have led to a significant increase in the surgical volume of TAA. While a majority of ankle arthritis is post-traumatic in nature, other causes include autoimmune or inflammatory conditions. Medical management of these conditions frequently requires chronic corticosteroid administration, which is a well-established risk factor for complications following surgery. The purpose of this study was to investigate the association between chronic preoperative steroid use and postoperative complications following TAA. Methods The American College of Surgeons National Surgical Quality Improvement (NSQIP) database was analyzed to identify all patients who underwent TAA between 2015 and 2020. Patient characteristics including demographics, comorbidities, surgical characteristics, and 30-day postoperative complication data were collected. The data was analyzed using bivariate and multivariate logistic regression to identify all postoperative complications associated with chronic preoperative steroid use. Results A total of 1,606 patients were included in this study: 1,533 (95.5%) were included in the non-steroid cohort, and 73 (4.5%) were included in the chronic steroid cohort. Chronic steroid use was significantly associated with female sex (p < 0.001) and American Society of Anesthesiologists (ASA) ≥3 (p < 0.001). Chronic steroid use was not associated with superficial surgical site infection (SSI) (p = 0.634) or wound dehiscence (p = 0.999). The postoperative complication that was significantly associated with chronic steroid use was sepsis (p = 0.031). After adjusting for female sex and the ASA grade, chronic steroid use was found to be independently associated with sepsis (p = 0.013). Conclusion Preoperative chronic steroid use is not associated with superficial SSI or wound dehiscence within 30 days following TAA. As TAA becomes a more attractive alternative to ankle arthrodesis, a better understanding of preoperative risk factors can aid in widening indications and knowing what patients are at risk for complications.

Higher modified frailty index score is associated with 30-day postoperative complications following simultaneous bilateral total knee arthroplasty.

BACKGROUND: There is no clear consensus regarding patient populations at highest risk for complications from simultaneous bilateral total knee arthroplasty (TKA). The purpose of this study was to determine whether the comorbidities comprising the modified Frailty Index (mFI) were correlated with poor outcomes following simultaneous bilateral TKA. METHODS: From 2006 to 2019, patients undergoing bilateral TKA aged 50 years or older were identified in a national database. The 5-item mFI was calculated based on the presence of five comorbidities: diabetes, congestive heart failure, hypertension, chronic obstructive pulmonary disease, and dependent functional status. Chi-squared and multivariable regression analyses were used to evaluate the association of mFI scores with postoperative complications. RESULTS: The study analyzed 8,776 patients with an average age of 65 years. After adjustment on multivariable regression analysis, compared to patients with a mFI score of 0, those with a score of 1 had an increased risk of pulmonary complication (OR 3.14; p = 0.011), renal problem (OR 12.86; p = 0.022), sepsis complication (OR 2.82; p = 0.024), postoperative transfusion (OR 1.19; p = 0.012), and non-home discharge (OR 1.17; p = 0.002).Patients with a score of 2 compared to 0 had similar complications when compared. These patients had an increased risk of cardiac complication (OR 4.84; p = 0.009) and prolonged hospital stay (OR 4.06; p < 0.001). CONCLUSION: Increased mFI scores were associated with significantly higher complication rates in patients undergoing simultaneous bilateral TKA compared to unilateral TKA. Our results can be used to identify which patients may need a staged bilateral TKA or preoperative optimization to safely undergo a simultaneous bilateral TKA. LEVEL OF EVIDENCE: III.