Risk Factors for Postoperative Complications Following Mandibular Fracture Repair.

Complications following mandibular fracture repair (MFR) may carry significant morbidity to patients. The purpose of our study is to determine the risk factors for postoperative complications following MFR. The authors conducted a retrospective cohort study of trauma patients who underwent MFR in 2018 and 2019. Excluded were patients below 18 years old and those with postoperative follow-up <2 weeks. The primary outcome was the incidence of major and minor postoperative complications following MFR. Of n=275 patients included, mean (SD) age was 35 (14) years and median (IQR) follow up was 49 (26-117) days. Most patients [n=208 (76%)] underwent both maxillomandibular/intermaxillary fixation (MMF/IMF) and open reduction and internal fixation (ORIF). The incidence of major postoperative complications was 19% (n=51) including malunion [n=8 (2.9%)], malocclusion [n=21 (7.6%)], and unplanned reoperation [n=26 (9.5%)]. The incidence of minor postoperative complications was 61% (n=167). Alcohol use at the time of surgery and greater MISS score were associated with greater odds of major complications [adjusted odds ratio (aOR) 95% CI: 3.4 (1.2-9.0), 1.09 (1.02-1.160), respectively]. Smoking at the time of surgery and moderately (>2 mm) and severely displaced fractures (>4 mm) were associated with greater odds of minor complications [aOR (95% CI): 2.1 (1.04-4.2), 2.7 (1.2-6.4), 2.7 (1.1-6.6), respectively]. Alcohol use, smoking, greater MISS score, and displaced fractures >2 mm were significant risk factors for postoperative complications following MFR. Our findings can help guide informed decision making and surgical planning in patients with mandibular fractures.

Sequence Matters: Primary COVID-19 Vaccination after Infection Elicits Similar Anti-spike Antibody Levels, but Stronger Antibody Dependent Cell-mediated Cytotoxicity than Breakthrough Infection.

Infection before primary vaccination (herein termed "hybrid immunity") engenders robust humoral immunity and broad Ab-dependent cell-mediated cytotoxicity (ADCC) across SARS-CoV-2 variants. We measured and compared plasma IgG and IgA against Wuhan-Hu-1 and Omicron (B.1.1.529) full-length spike (FLS) and receptor binding domain after three mRNA vaccines encoding Wuhan-Hu-1 spike (S) and after Omicron breakthrough infection. We also measured IgG binding to Wuhan-Hu-1 and Omicron S1, Wuhan-Hu-1 S2 and Wuhan-Hu-1 and Omicron cell-based S. We compared ADCC using human embryonic lung fibroblast (MRC-5) cells expressing Wuhan-Hu-1 or Omicron S. The effect of Omicron breakthrough infection on IgG anti-Wuhan-Hu-1 and Omicron FLS avidity was also considered. Despite Omicron breakthrough infection increasing IgG and IgA against FLS and receptor binding domain to levels similar to those seen with hybrid immunity, there was no boost to ADCC. Preferential recognition of Wuhan-Hu-1 persisted following Omicron breakthrough infection, which increased IgG avidity against Wuhan-Hu-1 FLS. Despite similar total anti-FLS IgG levels following breakthrough infection, 4-fold higher plasma concentrations were required to elicit ADCC comparable to that elicited by hybrid immunity. The greater capacity for hybrid immunity to elicit ADCC was associated with a differential IgG reactivity pattern against S1, S2, and linear determinants throughout FLS. Immunity against SARS-CoV-2 following Omicron breakthrough infection manifests significantly less ADCC capacity than hybrid immunity. Thus, the sequence of antigenic exposure by infection versus vaccination and other factors such as severity of infection affect antiviral functions of humoral immunity in the absence of overt quantitative differences in the humoral response.

Cardiac Surgical Bleeding, Transfusion, and Quality Metrics: Joint Consensus Statement by the Enhanced Recovery After Surgery Cardiac Society and Society for the Advancement of Patient Blood Management.

BACKGROUND: Excessive perioperative bleeding is associated with major complications in cardiac surgery, resulting in increased morbidity, mortality, and cost. METHODS: An international expert panel was convened to develop consensus statements on the control of bleeding and management of transfusion and to suggest key quality metrics for cardiac surgical bleeding. The panel reviewed relevant literature from the previous 10 years and used a modified RAND Delphi methodology to achieve consensus. RESULTS: The panel developed 30 consensus statements in 8 categories, including prioritizing control of bleeding, prechest closure checklists, and the need for additional quality indicators beyond reexploration rate, such as time to reexploration. Consensus was also reached on the need for a universal definition of excessive bleeding, the use of antifibrinolytics, optimal cessation of antithrombotic agents, and preoperative risk scoring based on patient and procedural factors to identify those at greatest risk of excessive bleeding. Furthermore, an objective bleeding scale is needed based on the volume and rapidity of blood loss accompanied by viscoelastic management algorithms and standardized, patient-centered blood management strategies reflecting an interdisciplinary approach to quality improvement. CONCLUSIONS: Prioritizing the timely control and management of bleeding is essential to improving patient outcomes in cardiac surgery. To this end, a cardiac surgical bleeding quality metric that is more comprehensive than reexploration rate alone is needed. Similarly, interdisciplinary quality initiatives that seek to implement enhanced quality indicators will likely lead to improved patient care and outcomes.

Maximizing Minimally Invasive Cardiac Surgery With Enhanced Recovery (ERAS).

We convened a group of cardiac surgeons, intensivists, and anesthesiologists with extensive experience in minimally invasive cardiac surgery (MICS) and perioperative care to identify the essential elements of a MICS program and the relationship with Enhanced Recovery After Surgery (ERAS). The MICS incision should minimize tissue invasion without compromising surgical goals. MICS also requires safe management of hemodynamics and preservation of cardiac function, which we have termed myocardial management. Finally, comprehensive perioperative care through an ERAS program should be provided to allow patients to achieve optimal recovery. Therefore, we propose that MICS requires 3 elements: (1) a less invasive surgical incision (non-full sternotomy), (2) optimized myocardial management, and (3) ERAS. We contend that the full benefit of MICS can be achieved only by also utilizing an ERAS platform.

The deubiquitinase USP9X regulates RIT1 protein abundance and oncogenic phenotypes.

RIT1 is a rare and understudied oncogene in lung cancer. Despite structural similarity to other RAS GTPase proteins such as KRAS, oncogenic RIT1 activity does not appear to be tightly regulated by nucleotide exchange or hydrolysis. Instead, there is a growing understanding that the protein abundance of RIT1 is important for its regulation and function. We previously identified the deubiquitinase USP9X as a RIT1 dependency in RIT1-mutant cells. Here, we demonstrate that both wild-type and mutant forms of RIT1 are substrates of USP9X. Depletion of USP9X leads to decreased RIT1 protein stability and abundance and resensitizes cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in vitro and in vivo. Our work expands upon the current understanding of RIT1 protein regulation and presents USP9X as a key regulator of RIT1-driven oncogenic phenotypes.

Modern multiligament knee injury surgical reconstruction techniques can achieve excellent knee function and patient satisfaction, with low complication rates.

PURPOSE: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. METHODS: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient-reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. RESULTS: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. CONCLUSIONS: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. LEVEL OF EVIDENCE: Level IV.

An Introduction to The Orbital Buttresses.

Facial buttresses are supportive bony structures of the facial skeleton that form a thick, strong, and protective framework for the face. Surgical fixation may be required to restore morphology and function when damage to these buttresses occurs. We sought to determine if, similar to buttresses of the facial skeleton, buttresses of the internal orbit exist. Hence, we analyzed 10 human cadaver skulls imaged by microcomputed tomography (micro-CT). Image processing and thickness/heat mapping were performed using Avizo and ImageJ softwares. After identifying the orbital buttresses, we reviewed CT scans of patients who had orbital fractures across three years to determine the frequency of fracture of the orbital buttresses. We identified 5 buttresses of the internal orbit: superomedial fronto-ethmoidal strut with the deep orbital buttress, inferomedial strut with the posterior ledge, inferior orbital fissure, sphenoid-frontal superolateral strut, and the sphenoid lip. The average threshold orbital buttress thickness was 1.36 (0.25) mm. A total of 1186 orbits of 593 individuals were analyzed for orbital buttress involvement. Orbital buttresses were spared in 770 (65%) orbits. The inferomedial strut with the posterior ledge was the most commonly fractured buttress in 14.4% of orbits (n=171), followed by the sphenoid strut and lip (66 [5.6%]). To our knowledge, this is the first description of the buttresses of the internal orbit. Orbital reconstruction for fracture repair or oncologic purposes requires the support of orbital buttresses. Understanding the anatomy of orbital buttresses is crucial for successful surgical planning, proper implant positioning, and restoration of function and appearance.

Efficacy of Antibody Drug Conjugates Alone and in Combination with other Agents in Metastatic Urothelial Carcinoma: A Scoping Review.

INTRODUCTION: Antibody drug conjugates represent a promising class of antineoplastic agents comprised of a monoclonal antibody linked to a potent cytotoxic payload for targeted delivery of chemotherapy to tumors. Various antibody drug conjugates have demonstrated impressive efficacy in patients with metastatic urothelial carcinoma in clinical trials, leading to two FDA approved therapies and several other agents and combinations in clinical development. MATERIALS AND METHODS: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens. RESULTS: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable. CONCLUSION: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.

Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model.

Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a 4-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared with controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase and transient receptor potential vanilloid 1. These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, noninvasive treatment strategy in orthopedic care.

Temporary Mechanical Circulatory Support after Cardiac Surgery.

Postcardiotomy shock in the cardiac surgical patient is a highly morbid condition characterized by profound myocardial impairment and decreased systemic perfusion inadequate to meet end-organ metabolic demand. Postcardiotomy shock is associated with significant morbidity and mortality. Poor outcomes motivate the increased use of mechanical circulatory support (MCS) to restore perfusion in an effort to prevent multiorgan injury and improve patient survival. Despite growing acceptance and adoption of MCS for postcardiotomy shock, criteria for initiation, clinical management, and future areas of clinical investigation remain a topic of ongoing debate. This article seeks to (1) define critical cardiac dysfunction in the patient after cardiotomy, (2) provide an overview of commonly used MCS devices, and (3) summarize the relevant clinical experience for various MCS devices available in the literature, with additional recognition for the role of MCS as a part of a modified approach to the cardiac arrest algorithm in the cardiac surgical patient.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC).

PURPOSE: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited. MATERIALS AND METHODS: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors. RESULTS: From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm (P < .001) and neurologic symptoms (P < .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 v 40 months, respectively; P = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96]; P = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; P < .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival. CONCLUSION: The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR- and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.

Progress towards World Health Organization HIV Infection 95-95-95 measures in Newfoundland and Labrador, Canada.

The HIV program in Newfoundland and Labrador (NL) provides care for all persons living with HIV (PLWH) in NL, yet progress toward UNAIDS 95-95-95 goals for diagnosis, linkage to care and viral suppression has not previously been documented. This analysis describes engagement in HIV care and virologic outcomes for the NL cohort in 2016 and 2019 and compares this data to the Canadian HIV Observational Cohort (CANOC). A retrospective review of the NL clinic included adults aged >18 years and descriptive statistics for demographics, risk factors, and clinical variables were assessed and compared using χ2 test or Fisher's Exact test (categorical) or Wilcoxon Sum Rank test (continuous). Engagement in care and virologic outcomes for the NL cohort were consistently high over the 2016 to 2019 period with > 98% on antiretroviral therapy (ART), and > 96% having a suppressed virus load. Engagement in care and virologic outcomes among PLWH in NL is high and compares favorably to a national cohort.

The Proposed Ninth Edition TNM Classification of Lung Cancer.

A universal nomenclature of the anatomic extent of lung cancer has been critical for individual patient care as well as research advances. As progress occurs, new details emerge that need to be included in a refined system that aligns with contemporary clinical management issues. The ninth edition TNM classification of lung cancer, which is scheduled to take effect in January 2025, addresses this need. It is based on a large international database, multidisciplinary input, and extensive statistical analyses. Key features of the ninth edition include validation of the significant changes in the T component introduced in the eighth edition, subdivision of N2 after exploration of fundamentally different ways of categorizing the N component, and further subdivision of the M component. This has led to reordering of the TNM combinations included in stage groups, primarily involving stage groups IIA, IIB, IIIA, and IIIB. This article summarizes the analyses and revisions for the TNM classification of lung cancer to familiarize the broader medical community and facilitate implementation of the ninth edition system.

The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial.

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

Cobalt ions induce a cellular senescence secretory phenotype in human synovial fibroblast-like cells that may be an early event in the development of adverse local tissue reactions to hip implants.

Objectives: Total hip arthroplasty is a successful procedure for treating advanced osteoarthritis (OA). Metal bearing surfaces remain one of the most widely implanted prosthesis, however approximately 10% of patients develop adverse local tissue reactions (ALTRs), namely lymphocytic predominant soft tissue reaction with or without necrosis and osteolysis resulting in high revision rates. The mechanism(s) for these reactions remains unclear although T lymphocyte mediated type IV hypersensitivity to cobalt (Co) and chromium (Cr) ions have been described. The purpose of this study was to determine the prolonged effects of Co and Cr metal ions on synovial fibroblasts to better understand the impact of the synovial membrane in the development of ALTRs. Methods: Human synovial fibroblast-like cells were isolated from donors undergoing arthroplasty. DNA content and Alamar blue assay were used to determine cellular viability against exposure to Co and Cr. A beta-galactosidase assay was used to determine the development of cellular senescence. Western blotting and RT-qPCR were employed to determine changes in senescent associated secretory factors, signaling and anti-oxidant enzyme expression. A fluorescent assay was used to measure accumulation of hydrogen peroxide. Results: We demonstrate that prolonged cobalt exposure results in a downregulation of the enzyme catalase resulting in cytosolic accumulation of hydrogen peroxide, decreased Akt activity and cellular senescence. Senescent fibroblasts demonstrated upregulation of proinflammatory cytokines IL-1ß and TNFα in addition to the neurotrophic factor NGF. Conclusion: Our results provide evidence that metal ions induce a senescent associated secretory phenotype in synovial fibroblasts that could contribute to the development of adverse local tissue reactions.

Traumatic Brain Injury in Patients With Frontal Sinus Fractures.

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force that may lead to short or long-term impairment. Traumatic brain injury has been reported in up to 83% of craniofacial fractures involving the frontal sinus. However, the risk factors for TBI at presentation and persistent neurological sequelae in patients with frontal sinus fractures remain largely unstudied. The authors aim to evaluate the prevalence and risk factors associated with TBI on presentation and neurological sequelae in these patients. The authors retrospectively reviewed patients who presented with traumatic frontal sinus fractures in 2019. The authors' primary outcome was the prevalence of concomitant TBI on presentation, which authors defined as any patient with neurological symptoms/signs on presentation and/or patients with a Glasgow Coma Scale <15 with no acute drug or alcohol intoxication or history of dementia or other neurocognitive disorder. The authors' secondary outcome was the incidence of neurological sequelae after 1 month of injury. Bivariate analysis and multivariate logistic regression were performed. A total of 56 patients with frontal sinus fractures were included. Their median (interquartile range) age was 47 (31-59) years, and the median (interquartile range) follow-up was 7.3 (1.3-76.5) weeks. The majority were males [n = 48 (85.7%)] and non-Hispanic whites [n = 35 (62.5%)]. Fall was the most common mechanism of injury [n = 15 (26.8%)]. Of the 56 patients, 46 (82.1%) had concomitant TBI on presentation. All patients who had combined anterior and posterior table frontal sinus fractures [n = 37 (66.1%)] had TBI on presentation. These patients had 13 times the odds of concomitant TBI on presentation [adjusted odds ratio (95% CI): 12.7 (2.3-69.0)] as compared with patients with isolated anterior or posterior table fractures. Of 34 patients who were followed up more than 1 month after injury, 24 patients (70.6%) had persistent neurological sequelae, most commonly headache [n = 16 (28.6%)]. Patients who had concomitant orbital roof fractures had 32 times the odds of neurological sequelae after 1 month of injury [adjusted odds ratio (95% CI): 32 (2.4->100)]. Emergency physicians and referring providers should maintain a high degree of suspicion of TBI in patients with frontal sinus fractures. Head computed tomography at presentation and close neurological follow-up are recommended for patients with frontal sinus fracture with combined anterior and posterior table fractures, as well as those with concomitant orbital roof fractures.