The Changing Epidemiology of Traumatic Spine Injuries: A Trends Analysis of 26 Years of Patients at a Major Level 1 Trauma Center in the United States.

BACKGROUND CONTEXT: Traumatic spinal injuries (TSI) are associated with high morbidity, mortality, and resource utilization. The epidemiology of TSI varies greatly across different countries and regions and is impacted by national income levels, infrastructure, and cultural factors. Further, there may be changes over time. It is essential to investigate TSI to gain useful epidemiologic information. However, there have been no recent studies on trends for TSI in the US, despite the changing population demographics, healthcare policy, and technology. As a result, re-examination is warranted to reflect how the modern era has affected the epidemiology of US spine trauma patients and their management. PURPOSE: To determine epidemiologic trends in traumatic spine injuries over time. STUDY DESIGN/SETTING: Retrospective analysis; level 1 trauma center in the United States. PATIENT SAMPLE: A total of 21,811 patients, between the years of 1996 and 2022, who presented with traumatic spine injury. OUTCOME MEASURES: Age, sex, race, Injury Severity Score, mechanism of injury, injury diagnosis, injury level, rate of operative intervention, hospital length of stay, intensive care unit length of stay, discharge disposition, in-hospital mortality. METHODS: Data was collected from our institutional trauma registry over a 26-year period. Inclusion criteria involved at least one diagnosis of vertebral fracture, spinal cord injury, spinal subluxation, or intervertebral disc injury. Exclusion criteria consisted of patients with no diagnosed spine injury or a diagnosis of strain only. A total of 21,811 patients were included in the analysis. Descriptive statistics were tabulated and ordinary least squares linear regression was conducted for trends analysis. RESULTS: Regression analysis showed a significant upward trend in patient age (+13.83 years, ß=+0.65/year, p<0.001), female sex (+2.7%, ß=+0.18%/year, p=0.004), falls (+10.5%, ß=+0.82%/year, p<0.001), subluxations (+12.8%, ß=+0.35%/year, p<0.001), thoracic injuries (+1.5%, ß=+0.28%/year, p<0.001), and discharges to subacute rehab (+15.9%, ß=+0.68%/year, p<0.001). There was a significant downward trend in motor vehicle crashes (-7.8%, ß=-0.47%/year, p=0.016), firearms injuries (-3.4%, ß=-0.19%/year, p<0.001), sports/recreation injuries (-2.9%, ß=-0.18%/year, p<0.001), spinal cord injuries (-11.25%, ß=-0.37%, p<0.001), complete spinal cord injuries (-7.6%, ß=-0.24%/year, p<0.001), and discharges to home (+4.5%, ß=-0.27%/year, p=0.011). CONCLUSIONS: At our institution, the average spine trauma patient has trended toward older females. Falls represent an increasing proportion of the mechanism of injury, on a trajectory to become the most common cause. With time, there have been fewer spinal cord injuries and a lower proportion of complete injuries. At discharge, there has been a surge in the utilization of subacute rehabilitation facilities. Overall, there has been no significant change in injury severity, rate of operative intervention, length of stay, or mortality.

Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells.

Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting the synthesis of sphingosine 1-phosphate (S1P) by sphingosine kinase-2 and elevating dihydroceramides by inhibition of dihydroceramide desaturase. The present studies sought to determine the potential therapeutic activity of opaganib in cell culture and xenograft models of NB. Cytotoxicity assays demonstrated that NB cells, including cells with amplified MYCN, are effectively killed by opaganib concentrations well below those that accumulate in tumors in vivo. Opaganib was shown to cause dose-dependent decreases in S1P and hexosylceramide levels in Neuro-2a cells, while concurrently elevating levels of dihydroceramides. As with other tumor cells, opaganib reduced c-Myc and Mcl-1 protein levels in Neuro-2a cells, and also reduced the expression of the N-Myc protein. The in vivo growth of xenografts of human SK-N-(BE)2 cells with amplified MYCN was suppressed by oral administration of opaganib at doses that are well tolerated in mice. Combining opaganib with temozolomide plus irinotecan, considered the backbone for therapy of relapsed or refractory NB, resulted in increased antitumor activity in vivo compared with temozolomide plus irinotecan or opaganib alone. Mice did not lose additional weight when opaganib was combined with temozolomide plus irinotecan, indicating that the combination is well tolerated. Opaganib has additive antitumor activity toward Neuro-2a tumors when combined with the checkpoint inhibitor anti-CTLA-4 antibody; however, the combination of opaganib with anti-PD-1 or anti-PD-L1 antibodies did not provide increased antitumor activity over that seen with opaganib alone. Overall, the data demonstrate that opaganib modulates sphingolipid metabolism and intracellular signaling in NB cells and inhibits NB tumor growth alone and in combination with other anticancer drugs. Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody.

Patients With Inflammatory Bowel Disease Are at Increased Risk of Hospitalization Due to Respiratory Syncytial Virus.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk of developing respiratory infections. Respiratory syncytial virus (RSV) is a common respiratory virus with adverse outcomes in older adults. This study aimed to determine whether patients with IBD are at increased risk of a serious infection due to RSV. METHODS: We conducted a retrospective study using the multi-institutional research network TriNetX to assess the risk of hospitalization in a cohort of patients with IBD compared with that in a non-IBD control cohort with RSV infection from January 1, 2007, to February 27, 2023. One-to-one (1:1) propensity score matching was performed for demographic variables and RSV risk factors between the 2 cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULTS: There were 794 patients in the IBD-RSV cohort and 93,074 patients in the non-IBD-RSV cohort. The mean age of the IBD-RSV cohort was 55.6 ± 20 years, 59% were female, 80% were White, and 56.9% had Crohn's disease. The IBD-RSV cohort was at an increased risk of hospitalization (aOR 1.30, 95% CI 1.06-1.59). There was no difference in the risk (aOR 0.83, 95% CI 0.58-1.19) of a composite outcome of hospitalization-related complications between the 2 cohorts. Recent systemic corticosteroid use (<3 months) was associated with an increased risk of hospitalization (aOR 1.86, 95% CI 1.30-2.59) in the IBD-RSV cohort. DISCUSSION: We found that adult patients with IBD and RSV infection are at an increased risk of hospitalization and may benefit from the new RSV vaccine recommended for adults aged 60 years and older.

The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy.

Fibrosis is a chronic pathology resulting from excessive deposition of extracellular matrix components that leads to the loss of tissue function. Pulmonary fibrosis can follow a variety of diverse insults including ischemia, respiratory infection, or exposure to ionizing radiation. Consequently, treatments that attenuate the development of debilitating fibrosis are in desperate need across a range of conditions. Sphingolipid metabolism is a critical regulator of cell proliferation, apoptosis, autophagy, and pathologic inflammation, processes that are all involved in fibrosis. Opaganib (formerly ABC294640) is the first-in-class investigational drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Opaganib inhibits key enzymes in sphingolipid metabolism, including sphingosine kinase-2 and dihydroceramide desaturase, thereby reducing inflammation and promoting autophagy. Herein, we demonstrate in mouse models of lung damage following exposure to ionizing radiation that opaganib significantly improved long-term survival associated with reduced lung fibrosis, suppression of granulocyte infiltration, and reduced expression of IL-6 and TNFα at 180 days after radiation. These data further demonstrate that sphingolipid metabolism is a critical regulator of fibrogenesis, and specifically show that opaganib suppresses radiation-induced pulmonary inflammation and fibrosis. Because opaganib has demonstrated an excellent safety profile during clinical testing in other diseases (cancer and COVID-19), the present studies support additional clinical trials with this drug in patients at risk for pulmonary fibrosis.

The Utility of the Validated Intraoperative Bleeding Scale in Thoracolumbar Spine Surgery: A Single-Center Prospective Study.

STUDY DESIGN: Prospective, single-center study. OBJECTIVE: To evaluate the clinical relevance of the validated intraoperative bleeding severity scale (VIBe) in thoracolumbar spine surgery. METHODS: Adult patients aged 18 through 88 undergoing elective decompression, instrumentation, and fusion of the thoracolumbar spine were prospectively enrolled after informed consent was provided and written consent was obtained. Validated intraoperative bleeding severity scores were recorded intraoperatively. Univariate analysis consisted of Student T-tests, Pearson's χ2 Tests, Fisher's Exact Tests, linear regression, and binary logistic regression. Multivariable regression was conducted to adjust for baseline characteristics and potential confounding variables. RESULTS: A total of N = 121 patients were enrolled and included in the analysis. After adjusting for confounders, VIBe scores were correlated with an increased likelihood of intraoperative blood transfusion (ß = 2.46, P = .012), postoperative blood transfusion (ß = 2.36, P = .015), any transfusion (ß = 2.49, P < .001), total transfusion volume (ß = 180.8, P = .020), and estimated blood loss (EBL) (ß = 409, P < .001). Validated intraoperative bleeding severity scores had no significant association with length of hospital stay, 30-day readmission, 30-day reoperation, 30-day emergency department visit, change in pre- to post-op hemoglobin and hematocrit, total drain output, or length of surgery. CONCLUSION: The VIBe scale is associated with perioperative transfusion rates and EBL in patients undergoing thoracolumbar spine surgery. Overall, the VIBe scale has clinically relevant meaning in spine surgery, and shows potential utility in clinical research. LEVEL OF EVIDENCE: Level II.

Lower Extremity Somatosensory Evoked Potentials Predict Functional Outcomes in Complete Traumatic Cervical Spinal Cord Injury.

BACKGROUND: Traumatic cervical spinal cord injury (tCSCI) is often a debilitating injury, making early prognosis important for medical and surgical planning. Currently, the best early predictors of prognosis are physical examination, imaging studies, and patient demographics. Despite these factors, patient outcomes continue to vary significantly. The purpose of this study was to evaluate the prognostic value of somatosensory evoked potentials (SSEPs) with functional outcomes in tCSCI patients. METHODS: A retrospective study was conducted on prospectively collected data from 2 academic institutions. Patients 18 years and older who had tCSCI and underwent posterior cervical decompression and stabilization with intraoperative neuromonitoring were reviewed. The outcomes of interest were the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade and ASIA motor score at follow-up. Outcomes measures were assessed via student t-tests, chi-squared tests, and multivariable regression analysis. RESULTS: A total of 79 patients were included. In complete injuries, detectable lower extremity SSEPs were associated with higher ASIA motor scores at follow-up (P = 0.002), greater increases in ASIA motor scores at follow-up (P = 0.009), and a greater likelihood of clinically important improvement in ASIA motor score (P = 0.024). Incomplete, AIS grade C injuries has higher rates of grade conversion (P = 0.019) and clinically important improvement in ASIA motor score (P = 0.010), compared to AIS grade A or B injuries. CONCLUSIONS: The detection of lower extremity SSEP signals during initial surgical treatment of tCSCI is associated with greater improvement in ASIA motor scores postoperatively. The association is most applicable to patients with complete injury.

Region-specific mouse brain ganglioside distribution revealed by an improved isobaric aminoxyTMT labeling strategy with automated data processing.

Gangliosides are specialized glycosphingolipids most abundant in the central nervous system. Their complex amphiphilic structure is essential to the formation of membrane lipid rafts and for molecular recognition. Dysfunction of lipid rafts and ganglioside metabolism has been linked to cancer, metabolic disorders, and neurodegenerative disorders. Changes in ganglioside concentration and diversity during the progression of disease have made them potential biomarkers for early detection and shed light on disease mechanisms. Chemical derivatization facilitates whole ion analysis of gangliosides while improving ionization, providing rich fragmentation spectra, and enabling multiplexed analysis schemes such as stable isotope labeling. In this work, we report improvement to our previously reported isobaric labeling methodology for ganglioside analysis by increasing buffer concentration and removing solid-phase extraction desalting for a more complete and quantitative reaction. Identification and quantification of gangliosides are automated through MS-DIAL with an in-house ganglioside derivatives library. We have applied the updated methodology to relative quantification of gangliosides in six mouse brain regions (cerebellum, pons/medulla, midbrain, thalamus/hypothalamus, cortex, and basal ganglia) with 2 mg tissue per sample, and region-specific distributions of 88 ganglioside molecular species are described with ceramide isomers resolved. This method is promising for application to comparative analysis of gangliosides in biological samples.

Ligand-Directed Metalation of a Gold Pyrazolate Cluster.

Solid "[AuL]" (HL = 3-[pyrid-2-yl]-5-tertbutyl-1H-pyrazole) can be crystallized as cyclic [Au3(µ-L)3] and [Au4(µ-L)4] clusters from different solvents. The crystalline tetramer contains a square Au4 core with an HT:TH:TH:HT arrangement of ligand substituents, which preorganizes the cluster to chelate to additional metal ions via its pendant pyridyl groups. The addition of 0.5 equiv of AgBF4 to [AuL] yields [Ag2Au4(µ3-L)4][BF4]2, where two edges of the Au4 square are spanned by Ag+ ions via metallophilic Ag···Au contacts. Treatment of [AuL] with [Cu(NCMe)4]PF6 affords the metalloligand helicate [Cu2Au2(µ-L)4][PF6]2, via oxidation of the copper and partial fragmentation of the cluster.

FLOSEAL Versus SURGIFLO in Lumbar Surgery: Similar Outcomes, Different Costs in a Matched Cohort Analysis.

OBJECTIVE: Flowable gelatin-based matrices with thrombin for hemostatic control are commercially available as Floseal (Baxter International Inc.) and Surgiflo (Ethicon Inc.). The objective of this study is to compare the rate of blood transfusions following the use of Floseal and Surgiflo in lumbar spine surgery. METHODS: Elective lumbar spine surgery patients between September 2019 and March 2021 were identified via CPT codes. Floseal 10 mL (N=102) and Surgiflo matrix 8 mL (N=108) cohorts excluded those younger than 18 years or those who underwent surgeries for infection, trauma, or tumor. The primary outcome was blood transfusion. Surgical complexity was controlled using the Surgical Invasiveness Index and Adult Spinal Deformity Invasiveness Score. The 1:1 propensity score matching was performed using demographic information, Surgical Invasiveness Index, Adult Spinal Deformity Invasiveness Score, and tranexamic acid use. RESULTS: A total of 77 Floseal patients were propensity score matched with 77 Surgiflo patients. There was no difference in the rate of blood transfusion (p=0.441). There was also no difference in operative time, estimated blood loss, or postoperative hemoglobin levels. The Surgiflo cohort used more units per surgery (p=0.004) and cost $102.45 more per surgery. Switching to Floseal saves $102,450 per year per 1000 surgeries. CONCLUSIONS: There was no difference in transfusion rates between using Floseal or Surgiflo for lumbar spine surgery. Surgiflo had higher usage per surgery and costs than Floseal.

Peak Pair Pruner: a post-processing software to MS-DIAL for peak pair validation and ratio quantification of isotopic labeling LC-MS(/MS) data.

Motivation: Isotopic labeling is an essential relative quantification strategy in mass spectrometry-based metabolomics, ideal for studying large cohorts by minimizing common sources of variations in quantitation. MS-DIAL is a free and popular general metabolomics platform that has isotopic labeling data processing capabilities but lacks features provided by other software specialized for isotopic labeling data analysis, such as isotopic pair validation and tabular light-to-heavy peak ratio reporting. Results: We developed Peak Pair Pruner (PPP), a standalone Python program for post-processing of MS-DIAL alignment matrixes. PPP provides these missing features and innovation including isotopic overlap subtraction based on a light-tagged pool sample as quality control. The MS-DIAL+PPP workflow for isotopic labeling-based metabolomics data processing was validated using light and heavy dansylated amino acid standard mixture and metabolite extract from human plasma. Availability and implementation: Peak Pair Pruner is freely available on Github: https://github.com/QibinZhangLab/Peak_Pair_Pruner. Raw MS data and .ibf files analyzed are on Metabolomics Workbench with Study ID ST002427. Contact: q_zhang2@uncg.edu. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Lower socioeconomic status is not associated with severity of adolescent idiopathic scoliosis: a matched cohort analysis.

PURPOSE: Assessing the influence of socioeconomic status (SES) on the severity of adolescent idiopathic scoliosis (AIS) on initial presentation to the spinal surgeon remains a challenge. The area deprivation index (ADI) is a validated measure of SES that abstracts multiple domains of disadvantage into a single score. We hypothesized that patients with low SES (high ADI) present to the orthopedic clinic with more advanced curve pathology. METHODS: We retrospectively reviewed patients diagnosed with AIS. Subjects were assigned ADI scores based on Zip codes. Matched cohorts of high and low ADI were generated using propensity scores. Bivariate and multivariate analyses were performed to identify factors impacting the magnitude of the curve at presentation. RESULTS: A total of 425 patients with appropriate imaging were included. After matching, the study population was 69.2% female and 92.3% Black. The mean BMI percentile was 61.9. Medicaid covered 57.3% of subjects, and 42.7% had commercial insurance. The mean ADI was 55.5. The mean Cobb angle at presentation was 33.6 degrees. Cobb angle was significantly greater among female patients (36.0 degrees vs 28.0) and among patients with greater BMI percentile (ß = 0.127), but was not significantly associated with ADI, race, or insurance type. ADI was not associated with the rate of surgery. CONCLUSION: ADI is not predictive of curve severity in pediatric patients presenting to the clinic for AIS. Female sex and BMI are independently associated with advanced curvature. Public health workers, primary care providers, and surgeons should remain aware of the complex interactions of socioeconomic factors, BMI and sex when addressing barriers to timely care. LEVEL OF EVIDENCE: Prognostic Level III.

Relative Energy Deficiency in Sport (RED-S): Scientific, Clinical, and Practical Implications for the Female Athlete.

Problem: If athletes develop low energy availability (LEA), it can lead to a Relative Energy Deficiency in Sport (RED-S) syndrome which has severe health consequences if not treated. Methodology: A narrative review of the most recent and pertinent literature on the topic, with special emphasis on women. Results: In assessing the current literature, we have synthesized: i) the scientific implications of LEA and RED-S, ii) the clinical manifestations of the conditions currently available for detection, as well as iii) the practical implications for healthcare and support for female athletes and teams in planning intervention or prevention strategies (maintaining EA >45 kcal/kg FFM/day). Discussion: The 'Female Athlete Triad" emerged in the 1990s as researchers understood more of the etiological adaptation of female athlete health to sports training. In the last 10 years, the scientific community has recognized that the 'Triad' approach was too narrow in focus, and the broader concept of RED-S emerged. Both the Triad and RED-S are consequences of a frequently prevalent LEA in athletes (<30 kcal/kg FFM/day). Developing LEA and RED-S compromises training adaptation, performance capacity, and health in athletes. For these reasons, it is critical that an athlete's support team recognize the behaviors that may indicate RED-S evolution. In this way, we can assist female athletes in reaching their full potential in sports while protecting their health.

Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy.

Exposure to ionizing radiation (IR) is a lingering threat from accidental or terroristic nuclear events, but is also widely used in cancer therapy. In both cases, host inflammatory responses to IR damage normal tissue causing morbidity and possibly mortality to the victim/patient. Opaganib, a first-in-class inhibitor of sphingolipid metabolism, has broad anti-inflammatory and anticancer activity. Opaganib elevates ceramide and reduces sphingosine 1-phosphate (S1P) in cells, conditions that increase the antitumor efficacy of radiation while concomitantly suppressing inflammatory damage to normal tissue. Therefore, opaganib may suppress toxicity from unintended IR exposure and improve patient response to chemoradiation. To test these hypotheses, we first examined the effects of opaganib on the toxicity and antitumor activity of radiation in mice exposed to total body irradiation (TBI) or IR with partial bone marrow shielding. Oral treatment with opaganib 2 h before TBI shifted the LD75 from 9.5 Gy to 11.5 Gy, and provided substantial protection against gastrointestinal damage associated with suppression of radiation-induced elevations of S1P and TNFα in the small intestines. In the partially shielded model, opaganib provided dose-dependent survival advantages when administered 4 h before or 24 h after radiation exposure, and was particularly effective when given both prior to and following radiation. Relevant to cancer radiotherapy, opaganib decreased the sensitivity of IEC6 (non-transformed mouse intestinal epithelial) cells to radiation, while sensitizing PAN02 cells to in vitro radiation. Next, the in vivo effects of opaganib in combination with radiation were examined in a syngeneic tumor model consisting of C57BL/6 mice bearing xenografts of PAN02 pancreatic cancer cells and a cross-species xenograft model consisting of nude mice bearing xenografts of human FaDu cells. Mice were treated with opaganib and/or IR (plus cisplatin in the case of FaDu tumors). In both tumor models, the optimal suppression of tumor growth was attained by the combination of opaganib with IR (± cisplatin). Overall, opaganib substantially protects normal tissue from radiation damage that may occur through unintended exposure or cancer radiotherapy.

Intraoperative Sensory Signals Predict Prognosis for Patients with Traumatic Cervical Spinal Cord Injury.

OBJECTIVE: In patients with traumatic cervical spinal cord injury (tCSCI), the potential role of intraoperative neuromonitoring as a prognostic tool has been insufficiently studied. This study aimed to determine if detectable signals during intraoperative neuromonitoring portend a greater likelihood of recovery for patients with tCSCI. METHODS: Patients who underwent decompression and surgical fixation following tCSCI were retrospectively reviewed through previously prospectively collected data from the Surgical Timing in Acute Spinal Cord Injury Study. Improvement in American Spinal Injury Association (ASIA) motor score and ASIA Impairment Scale grade conversion rates at final follow-up were compared between patients with detectable intraoperative neuromonitoring somatosensory evoked potential (SSEP) signals and those without detectable signals. RESULTS: Forty-nine patients had intraoperative neuromonitoring. Patients with incomplete tCSCI had detectable lower extremity SSEPs more often than patients with complete tCSCI (56.3% vs. 23.5%, P = 0.028). There was no difference in detectable upper extremity SSEPs between complete and incomplete tCSCI (65.6% vs. 58.8%, P = 0.638). Of the 17 patients with complete tCSCI, patients with detectable lower extremity SSEPs had ASIA motor scores similar to the nondetectable cohort on admission (21.5 vs. 16.2, P = 0.609) but higher ASIA motor scores at final follow-up (57.5 vs. 27.1, P = 0.041). Of the 32 patients with incomplete spinal cord injury, there was no difference in grade conversion or motor scores between detectable and nondetectable SSEP cohorts. CONCLUSIONS: The presence of upper extremity SSEP signals in patients who present with complete tCSCI portends greater improvement in ASIA motor scores and likelihood of American Spinal Injury Association Impairment Scale grade conversion at final follow-up.

Evading the host response: Staphylococcus "hiding" in cortical bone canalicular system causes increased bacterial burden.

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this "limb salvage" surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar-canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

Comparison of Dexamethasone 4mg vs 8mg Doses in Total Joint Arthroplasty Patients: A Retrospective Analysis.

Introduction Dexamethasone is commonly administered intraoperatively to control postoperative nausea and vomiting (PONV) and pain. There is limited evidence of the ideal dosage of dexamethasone during surgery. Dexamethasone administration may increase blood glucose levels, posing unique challenges in maintaining acceptable blood glucose levels in patients with diabetes. Objective Compare two doses of dexamethasone (4mg and 8mg) for outcomes in patients undergoing hip and knee arthroplasty. Methods Medical records of 3,194 patients having undergone total hip arthroplasty (THA) and total knee arthroplasty (TKA) between January 1, 2016 and December 31, 2017 who were administered dexamethasone were reviewed. The eligible population included male and female patients aged 18-89, who underwent elective hip and knee replacement surgery and were administered dexamethasone intraoperatively. Demographics, clinical variables, and preoperative diabetic status were recorded. Primary outcomes included: blood glucose levels, incidence of PONV, post-anesthesia care unit (PACU) time, and length of stay (LOS). Postoperative complications such as periprosthetic joint injection and urinary tract infections (UTI) were also examined within 90 days of surgery. The 30-day readmissions rate was also collected for analysis. Results There was no PONV in the entire patient population. There were no significant differences between 4mg and 8mg dexamethasone in patients with or without diabetes, for preop to postop blood glucose difference, surgical timing, and post-operative complications. Conclusion Dexamethasone in both 4mg and 8mg dose was effective in PONV prophylaxis. The effects of 4mg and 8mg dexamethasone were the same in individuals with and without diabetes and the increases in blood glucose were not significantly different. Dexamethasone should not be withheld, as its benefits seem to outweigh the risks even in patients with diabetes.

Kinematics and EMG activity in Reverse Total Shoulder Arthroplasty.

INTRODUCTION: Patients undergoing a Reverse Total Shoulder Arthroplasty (RTSA) often have functional limitations that affect the range of motion of the shoulder. These limitations are not mechanical in nature, but instead linked to a reduced ability to generate muscle force. The specific aims of this study was to offer a comparison between the muscle activity generated by a post-operative RTSA shoulder in a patient to that of their contralateral shoulder during a series of functional activities. MATERIAL & METHODS: A convenience sample of 10 subjects between the ages of 50-75 years of age were recruited. EMG and kinematic data were concomitantly collected while subjects completed tasks that included common activities of daily living. RESULTS: The main findings of this study were that all sub regions of the deltoid functioned as abductors, versus the native shoulder where the middle deltoid primarily works in abduction. For the scapular elevation activity there was a significant difference in flexion between the surgical and contralateral shoulder (p < .001), with the surgical shoulder having nearly 30° less range of motion. CONCLUSION: Anticipating limitations in functional outcomes and range of motion for patients after RTSA may inform patient decision-making and improve clinical evaluations. The finding of increased mid deltoid function during lifting activity has implications for rehabilitation and encouraging protocols that strengthen the deltoid in concentric motions. Additionally, the decreased scapular elevation found in this study may guide rehabilitation focusing on regaining range of motion post-operatively.

Lessons learned from a pilot randomized clinical trial of home-based exercise prescription before allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) is a life-saving technology that can cure otherwise incurable diseases, but imposes significant physiologic stress upon recipients. This stress leads to short-term toxicity and mid- to long-term physical function impairment in some recipients. Exercise interventions have demonstrated preliminary efficacy in preserving physical function in HCT recipients, but the role of these interventions prior to HCT (prehabilitative) is less known. We tested a 5- to 12-week, prehabilitative higher intensity home-based aerobic exercise intervention in a randomized study of alloHCT candidates. Of 113 patients screened, 34 were randomized to control or intervention groups, 16 underwent pre- and post-intervention peak oxygen consumption (VO2peak) testing, and 12 underwent pre- and post-intervention 6-min walk distance (6MWD) testing. No significant differences in VO2peak or 6MWD were seen pre- to post-intervention between intervention and control groups, but final numbers of evaluable participants in each group were too small to draw inferences regarding the efficacy of the intervention. We conclude that the design of our prehabilitative intervention was not feasible in this pilot randomized study, and make recommendations regarding the design of future exercise intervention studies in alloHCT.

Novel in vivo mouse model of shoulder implant infection.

BACKGROUND: Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement. METHODS: A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 µL of 1 × 103 (e3), or 1 × 104 (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 µL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed. RESULTS: Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence. DISCUSSION: Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII. CONCLUSION: The development of this model provides a foundation to study new therapeutics, interventions, and host modifications.