Characterization of patient population receiving bioactive glass bone graft substitute as intraoperative treatment for orthopaedic trauma fractures.

Background: Bioactive glass synthetic bone grafts are used to treat osseous defects in orthopaedic surgery. Characterization of the clinical scenarios associated with bioactive glass use in the context of orthopaedic trauma, are not well established. This study aims to characterize population demographics, operative variables, as well as postoperative variables, for patients who required bone grafting for treatment of traumatic orthopaedic injuries and received a bioactive glass bone substitute intraoperatively. Methods: The electronic medical record at a large Level I trauma center was queried for fracture patients between January 1st, 2019, and April 30th, 2022. Our retrospective cohort included fracture patients who received Fibergraft Matrix or Fibergraft Putty intraoperatively, and their respective control groups. This study ascertained patient demographic variables, operative variables, and postoperative variables. Differences in categorical variables were tested with Fischer's Exact Tests, while differences in continuous variables were tested with ANOVA. Statistical significance was determined as P < 0.05. If the overall Group model was significant for a given variable, post-hoc Fischer's Exact or Tukey HSD tests were used to assess pairwise significance between individual Group pairs. Results: A total of four categories across our analysis of demographic, operative, and postoperative variables displayed significant differences amongst subject Groups (P ≤ 0.03). Individual groups were compared such that significant differences between subject groups could be appreciated for a specific variable. FM subjects had greater length of surgery, billable costs, and vitamin D supplementation at the time of surgery compared to FM controls. Similarly, FP subjects had greater length of surgery, billable cost, and implants used intraoperatively compared to FP controls. Conclusion: This analysis revealed Fibergraft patients to have greater length of surgery and billable cost, with respect to their matched controls. These data suggest that Fibergraft patients had more severe orthopaedic fractures compared to matched controls.

Safe transport of spica casted infants: Reducing the risk of traumatic injury in side impact collisions.

BACKGROUND: There is limited data on transporting small children in hip spica casts used to treat pediatric femur fractures. Specific challenges include the fixed position of the body in the casted position and the increased size of the child due to cast thickness. Additionally, children less than 2 years old are recommended to be rear facing during transportation. This traveling position requires seats that are specifically designed to accommodate the small size of the child as well as accommodate the rear facing position. While seats able to accommodate casted children are available, it is unclear if they provide adequate protection in side impact collisions for rear facing spica casted infants. Therefore, the aim of this study was to evaluate traumatic injury metrics in a side impact collision model where a spica casted infant crash dummy was restrained in currently available car seats. METHODS: Two seats designed for spica casted children (R82 Quokka, Merritt Wallenberg) and two traditional car seats (Britax Emblem, Graco Sequel) able to accommodate a casted one-year-old crash test dummy were identified. Side impact collision testing was performed with the dummy positioned in the rear facing position and injury metrics recorded. RESULTS: Testing identified contact between the dummy's head and the door panel for a specialty spica car seat without protective side-wings for the head. All other seats contained side wings and prevented door-head contact. CONCLUSIONS: Casted children should be transported in a seat able to accommodate the cast and safely restrain them. Our results demonstrate the importance of side wing protection in any seat used to transport these children as side bolsters may help decrease the potential for head contact with the door and lower the risk of severe head injury.

Analysis of restraint use in pregnant versus non-pregnant populations involved in motor vehicle collisions.

BACKGROUND: Traumatic injuries obtained by pregnant females in motor vehicle collisions present unique treatment challenges for trauma and orthopaedic surgeons. Understanding safety choices in this population can help physicians and public safety advocates in delivering effective and targeted safety messages. METHODS: A publicly available, de-identified national data set that documents crash information (NASS-CDS) was examined to identify cohorts of pregnant and non-pregnant vehicle occupants and regression analysis employed to identify factors associated with belt non-use. RESULTS: Pregnant women were found to have significantly lower rates of belt use compared to non-pregnant females (70.0% vs. 90.3%, Rao-Scott Sample Weighted Chi-Square p = 0.0265). Logistic regression identified younger age and sitting in the back seat as associated with lower rates of belt use. CONCLUSION: Pregnant women wear belts at significantly lower frequencies than non-pregnant women and youth and second row seating increase noncompliance rates. This work suggests the need for targeted intervention strategies to improve belt compliance.

Injury metrics are altered in spica-casted versus non-casted child ATDs in side-impact collisions with door intrusion.

Objective: There is little data defining safe transport protocols for spica-casted children. A single earlier study demonstrated the presence of a body cast alters kinematics and injury metrics during simulated side-impact crashes. Since then, the National Highway Transportation Safety Administration (NHTSA) proposed a new side-impact test protocol for evaluating child restraints. This test is more severe than the earlier tests, as it simulates an impact with a door intruding into the occupant space. As no currently available child restraint system (CRS) able to accommodate a spica-casted child has been evaluated using these updated testing criteria, the objective of this study was to evaluate current restraint options in simulated side-impact collisions using an anthropomorphic test device (ATD) modeled after a 3-year-old.Methods: Four commercially available CRSs able to accommodate a spica-casted Q3s side-impact ATD were selected for testing. Side-impact testing was performed using casted and uncasted ATDs in compliance with the NHTSA proposed side-impact test. High-speed photography and ATD instrumentation were used to measure selected injury criteria.Results: HIC15 values were highest in CRSs with less robust side wings, such as the Merritt WallenburgTM (HIC15 = 1,373), which allow for the occupant to interact with the intruding door panel. Head contact with the door panel was found to correspond with high resultant neck peak force. Pelvic acceleration magnitudes were greatest for the uncasted tests. Casted tests with a CRS that included an armrest were associated with greater torso rotation in the frontal plane with the left shoulder moving toward the door panel.Conclusions: The presence of a spica cast alters injury metrics in side-impact testing. Spica specific child safety seats are not yet optimized for side-impact with door intrusion. This is due to a lack of adequate side cushion wings, which may place both casted and uncasted occupants at increased likelihood for injury through head contact with an intruding door. Additional work is needed to improve the safety of CRSs for both casted and uncasted children in side-impact collisions.

Prescribing and Consumption of Opioids After Primary, Unilateral Total Hip and Knee Arthroplasty in Opioid-Naive Patients.

BACKGROUND: This cohort study was designed to determine the discrepancy between the quantity of opioid prescribed vs that which was consumed after total knee arthroplasty (TKA) and total hip arthroplasty (THA) in opioid-naive patients. METHODS: Seven hundred twenty-three opioid-naive patients (426 TKAs and 297 THAs) from 7 hospitals in Michigan were contacted within 3 months of their surgery. Opioid prescribing and self-reported consumption was calculated in oral morphine equivalents (OMEs). Secondary outcomes included opioid refill in the first 90 days, pain in the first 7 days post-operatively, and satisfaction with pain care. RESULTS: For TKA, the mean prescribing was 632 mg OME (±229), and the mean consumption was 416 mg (±279). For THA, the mean prescribing was 584 mg OME (±335), and the mean consumption was 285 mg (±301). There were no associations between the amount of opioid prescribed and the likelihood of refill, post-operative pain, or satisfaction with pain control. The amount of opioid prescribed was associated with increased consumption, such that each increase of 1 pill was associated with approximately an additional half pill consumed after adjusting for other covariates. Moreover, 48.2% felt that they received "More" or "Much more" opioid than they needed. CONCLUSION: We recommend no more than 50 tablets of 5 mg oxycodone or its equivalent after TKA and 30 tablets after THA. Although dose reductions in other surgeries have not resulted in harm, continued assessment is needed to ensure that there are no unintended effects of opioid reduction, including worsened pain, decreased satisfaction, emergency department visits, or hospital readmissions. LEVEL OF EVIDENCE: Level III; Retrospective, cohort study.

Frontal Crash Injury Metrics Are Below Mandated Limits for a Spica Casted Child Dummy in Currently Available Restraints.

BACKGROUND: There is a paucity of data defining safe transport protocols for children treated with hip spica casting. Although restraint devices for casted children are available, all federally mandated testing uses a noncasted anthropomorphic test device (ATD or crash dummy). The purpose of this study was to evaluate current restraint options in simulated frontal crash testing using a casted pediatric ATD to determine injury risk to the head, cervical spine, chest, and pelvis. METHODS: Using a 3-year-old ATD, dynamic crash sled tests simulating frontal crash were performed in accordance with government safety standards. The ATD was casted in a double-leg spica and the following restraint devices were tested: a seat designed for spica casted children, a restraint vest-harness, a traditional booster seat, and 2 traditional forward-facing car seats. RESULTS: Although the presence of the cast increased many of the injury metrics measured, all seats passed current federal guidelines for the head and chest. No single seat performed best in all metrics. The greatest magnitude of neck loading and second-highest head injury criterion values were observed for the booster seat. The vest-harness produced the highest head injury criterion and the chest compression exceeded proposed federal limits. CONCLUSIONS: The results suggest safe transport in commercially available seats is possible with the child properly restrained in a correctly fitting seat. However, parents should not assume a child restraint system is appropriate for use just based on fit as, for example, seats with harnesses outperformed an easy to fit booster seat. CLINICAL RELEVANCE: Each child and the position of the child's cast are unique and discharge planning involves consideration of safe transportation. Although this study suggests several seats used to transport spica casted children pass the federal head and chest injury prevention requirements, it is important to recognize that some children may still require emergency vehicle transport.

A baculovirus-conjugated mimotope vaccine targeting Mycobacterium tuberculosis lipoarabinomannan.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a major cause of morbidity and mortality worldwide. However, an effective vaccine for M. tuberculosis is lacking. We panned a phage display library using monoclonal antibodies against M. tuberculosis liporabinomannan (LAM), an important component of the M. tuberculosis cell wall, and identified two peptide sequences, HSFKWLDSPRLR or SGVYKVAYDWQH, with high antibody affinity after multiple rounds of panning. Only the HSFKWLDSPRLR peptide induced an anti-LAM response when conjugated to either keyhole limpet hemocyanin (KLH) or to the baculovirus Autographa californica multicapsid nucleopolyherovirus (AcMNPV) when introduced into mice by injection or via intranasal inoculation, respectively. Vaccination with AcMNPV conjugated HSFKWLDSPRLR peptide delayed mortality in a mouse model of tuberculosis. Thus, we report a proof of principle M. tuberculosis vaccination strategy combining an anti-LAM mimotope with a baculovirus delivery system.

Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth.

Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis.

Activation of the DNA-dependent cytosolic surveillance pathway in response to Mycobacterium tuberculosis infection stimulates ubiquitin-dependent autophagy and inflammatory cytokine production, and plays an important role in host defense against M. tuberculosis. However, the identity of the host sensor for M. tuberculosis DNA is unknown. Here we show that M. tuberculosis activated cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) in macrophages to produce cGAMP, a second messenger that activates the adaptor protein stimulator of interferon genes (STING) to induce type I interferons and other cytokines. cGAS localized with M. tuberculosis in mouse and human cells and in human tuberculosis lesions. Knockdown or knockout of cGAS in human or mouse macrophages blocked cytokine production and induction of autophagy. Mice deficient in cGAS were more susceptible to lethality caused by infection with M. tuberculosis. These results demonstrate that cGAS is a vital innate immune sensor of M. tuberculosis infection.

Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus.

Mycobacterium tuberculosis (Mtb), the primary causative agent of human tuberculosis, has killed more people than any other bacterial pathogen in human history and remains one of the most important transmissible diseases worldwide. Because of the long-standing interaction of Mtb with humans, it is no surprise that human mucosal and innate immune cells have evolved multiple mechanisms to detect Mtb during initial contact. To that end, the cell surface of human cells is decorated with numerous pattern recognition receptors for a variety of mycobacterial ligands. Furthermore, once Mtb is ingested into professional phagocytes, other host molecules are engaged to report on the presence of an intracellular pathogen. In this review, we discuss the role of specific mycobacterial products in modulating the host's ability to detect Mtb. In addition, we describe the specific host receptors that mediate the detection of mycobacterial infection and the role of individual receptors in mycobacterial pathogenesis in humans and model organisms.

The ubiquitin ligase parkin mediates resistance to intracellular pathogens.

Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson's disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.