The hip fracture assessment tool: A scoring system to assess high risk geriatric hip fracture patients for post-operative critical care monitoring.

INTRODUCTION: Intensive care unit risk stratification models have been utilized in elective joint arthroplasty; however, hip fracture patients are fundamentally different in their clinical course. Having a critical care risk calculator utilizing pre-operative risk factors can improve resourcing for hip fracture patients in the peri­operative period. METHODS: A cohort of geriatric hip fracture patients at a single institution were reviewed over a three-year period. Non-operative patients, peri­implant fractures, additional procedures performed under the same anesthesia period, and patients admitted to the intensive care unit (ICU) prior to surgery were excluded. Pre-operative laboratory values, Revised Cardiac Risk Index (RCRI), and American Society of Anesthesiologists (ASA) scores were calculated. Pre-operative ambulatory status was determined. The primary outcome measure was ICU admission in the post-operative period. Outcomes were assessed with Fisher's exact test, Kruskal-Wallis test, logistic regression, and ROC curve. RESULTS: 315 patient charts were analyzed with 262 patients meeting inclusion criteria. Age ≥ 80 years, ASA ≥ 4, pre-operative hemoglobin < 10 g/dL, and a history of CVA/TIA were found to be significant factors and utilized within a "training" data set to create a 4-point scoring system after reverse stepwise elimination. The 4-point scoring system was then assessed within a separate "validation" data set to yield an ROC area under the curve (AUC) of 0.747. Score ≥ 3 was associated with 96.8 % specificity and 14.2 % sensitivity for predicting post-op ICU admission. Score ≥ 3 was associated with a 50 % positive predictive value and 83 % negative predictive value. CONCLUSION: A hip fracture risk stratification scoring system utilizing pre-operative patient specific values to stratify geriatric hip patients to the ICU post-operatively can improve the pre-operative decision-making of surgical and critical care teams. This has important implications for triaging vital hospital resources. LEVEL OF EVIDENCE: III (retrospective study).

Oral Prednisone Use Following Primary Total Knee Arthroplasty Does Not Increase Infections, But Can be Associated with Higher Risk for Medical and Surgical Complications.

INTRODUCTION: Postoperative use of oral prednisone to augment the effect of multimodal pain regimens after total knee arthroplasty (TKA) has increased in popularity. However, data on the risks of its utilization, especially as it relates to infection, has been lacking. We tested the null hypothesis that perioperative prednisone use is not associated with the incidence of surgical and medical complications after TKA. METHODS: Using a national administrative claims database, we identified 949,555 patients undergoing primary TKA. We excluded patients who filled oral prednisone prescriptions within 90 days prior to surgery or between 90 and 364 days after surgery. Patients who had acute prednisone use were defined as those who filled prednisone prescriptions only within 30 days after surgery. Outcomes consisted of surgical and medical complications after TKA. Multivariable logistic regression models were used to evaluate the association between acute prednisone use and complications, adjusting for age, sex, region, insurance plan, and Elixhauser comorbidities. RESULTS: Patients in the acute prednisone cohort had greater adjusted odds of subsequent manipulation under anesthesia (adjusted OR [odds ratio] = 1.23 [95% CI (confidence interval): 1.09 to 1.38]; P < 0.001) and lysis of adhesions (adjusted OR = 1.58 [95% CI: 1.02 to 2.33]; P = 0.03) compared to patients who did not have acute prednisone use. Patients who had acute prednisone use also had greater adjusted odds of acute kidney injury (adjusted OR = 1.47 [95% CI: 1.25 to 1.71]; P < 0.001) and pneumonia (adjusted OR = 4.04 [95% CI: 3.53 to 4.59]; P < 0.001). There was no increased incidence of infection. CONCLUSION: Prednisone use shortly following TKA may be associated with a higher incidence of certain surgical and medical complications, but without increased risk for infection. However, given these risks, the optimal patient profile for postoperative prednisone use remains to be defined.

Acute Total Hip Arthroplasty Following Acetabular Fracture is Associated With a High Risk of Revision, Dislocation, and Periprosthetic Fracture.

BACKGROUND: The aim of this study was to compare outcomes between acute, subacute, and delayed arthroplasty for acetabular fractures occurring within 1 week, from 1 week to 6 months, or more than 6 months before the index total hip arthroplasty (THA), versus THA without a history of acetabular fracture as a control. METHODS: We analyzed the records of patients undergoing primary THA who were enrolled in a national database for at least 2 years before and after the index procedure. Patients who had an initial diagnostic code for acetabular fracture occurring less than 1 week, from 1 week to 6 months, or at least more than 6 months before the THA were classified as acute THA (aTHA), subacute THA (saTHA), or delayed THA (dTHA), respectively. The control group was patients undergoing THA who did not have a history of acetabular fracture. There were 430,349 control primary THAs, 462 aTHAs, 675 saTHAs, and 1,162 dTHAs. RESULTS: After adjusting for age, sex, region, and comorbidities, patients who had an aTHA and saTHA experienced statistically significant increased odds of revision, dislocation, and periprosthetic fracture compared to primary THA without a history of acetabular fracture. Similarly, dTHA was associated with increased odds of revision, dislocation, and periprosthetic fractures compared to primary THA. In the multivariate analysis, aTHA had statistically significant higher rates of dislocation when compared to dTHA. CONCLUSIONS: Patients who had a history of acetabular fractures undergoing aTHA, saTHA, or dTHA have significantly increased rates of revision, periprosthetic fracture, and dislocation compared to primary THA in those who did not have a history of acetabular fractures.

Treatment approach for coexisting chest wall fractures and unstable thoracolumbar spine fractures in polytrauma patients requiring prone spine surgery.

Concomitant chest wall fractures (sternal and/or rib fractures) with unstable thoracolumbar fractures that require surgical fixation are rare but highly morbid injuries that mandate a multidisciplinary approach to treatment. There is limited evidence in the literature regarding optimal timing and order of surgical fixation of these patients with multiple injuries. Here, we present our experience with two patients at a single institution that demonstrates the challenges that present with this patient population. We advocate for earlier fixation of the chest wall fractures in the appropriately indicated patients, prior to prone positioning for spinal fixation.

Medicaid Insurance is Associated With Decreased MRI Use for Ankle Sprains Compared With Private Insurance: A Retrospective Database Analysis.

BACKGROUND: Advanced imaging modalities are expensive, and access to advanced imaging services may vary by socioeconomic factors, creating the potential for unwarranted variations in care. Ankle sprains are a common injury for which variations in MRI use can occur, both via underuse of indicated MRIs (appropriate use) and overuse of nonindicated MRIs (inappropriate use). High-value, equitable healthcare would decrease inappropriate use and increase appropriate use of MRI for this common injury. It is unknown whether socioeconomic factors are associated with underuse of indicated MRIs and overuse of nonindicated MRIs for ankle sprains. QUESTIONS/PURPOSES: Using ankle sprains as a paradigm injury, given their high population incidence, we asked: (1) Does MRI use for ankle sprains vary by insurance type? (2) After controlling for relevant confounding variables, did patients who received an MRI have higher odds of undergoing ankle surgery? METHODS: Between 2011 and 2019, a total of 6,710,223 patients were entered into the PearlDiver Mariner Patient Records Database with a diagnosis of ankle sprain. We considered patients with continuous enrollment in the database for at least 1 year before and 2 years after the diagnosis as potentially eligible. Based on that, 68% (4,567,106) were eligible; a further 20% (1,372,478) were excluded because of age younger than 18 years, age at least 65 years with Medicaid insurance, or age < 65 years with Medicare insurance. Another 0.1% (9169) had incomplete data, leaving 47% (3,185,459) for analysis here. Patients with Medicaid insurance differed from patients with Medicare Advantage or private insurance with respect to age, gender, region, and comorbidity burden. The primary outcome was ankle MRI occurring within 12 months after diagnosis. The use of ankle surgery after MRI in each cohort was measured as a secondary outcome. We used multivariable logistic regression models to evaluate the association between insurance type and MRI use while adjusting for age, gender, region, and comorbidity burden. Separate multivariable regression models were created to evaluate the association between receiving an MRI and subsequent ankle surgery for each insurance type, adjusting for age, gender, region, and comorbidity burden. Within 12 months of an ankle sprain diagnosis, 1% (3522 of 339,457) of patients with Medicaid, 2% (44,793 of 2,627,288) of patients with private insurance, and 1% (1660 of 218,714) of patients with Medicare Advantage received an MRI. RESULTS: After controlling for age, gender, region, and comorbidity burden, patients with Medicaid had lower odds of receiving an MRI within 12 months after ankle sprain diagnosis than patients with private insurance (odds ratio 0.60 [95% confidence interval 0.57 to 0.62]; p < 0.001). Patients with Medicaid who received an MRI had higher adjusted odds of undergoing subsequent ankle surgery (OR 23 [95% CI 21 to 26]; p < 0.001) than patients with private insurance (OR 12.7 [95% CI 12 to 13]; p < 0.001). CONCLUSION: Although absolute MRI use was generally low, there was substantial relative variation by insurance type. Given the high incidence of ankle sprains in the general population, these relative differences can translate to tens of thousands of MRIs. Further studies are needed to evaluate the reasons for decreased appropriate MRI use in patients with Medicaid and overuse of MRI in patients with private insurance. The establishment of clinical practice guidelines by orthopaedic professional societies and more stringent gatekeeping for MRI use by health insurers could reduce unwarranted variations in MRI use. LEVEL OF EVIDENCE: Level III, prognostic study.

Impact of Preoperative Opioid Use on 2-Year Patient-Reported Outcomes in Knee Surgery Patients.

The objectives of this study are to assess perioperative opioid use in patients undergoing knee surgery and to examine the relationship between preoperative opioid use and 2-year postoperative patient-reported outcomes (PROs). We hypothesized that preoperative opioid use and, more specifically, higher quantities of preoperative opioid use would be associated with worse PROs in knee surgery patients. We studied 192 patients undergoing knee surgery at a single urban institution. Patients completed multiple PRO measures preoperatively and 2-year postoperatively, including six patient-reported outcomes measurement information system (PROMIS) domains; the International Knee Documentation Committee (IKDC) questionnaire, numeric pain scale (NPS) scores for the operative knee and the rest of the body, Marx's knee activity rating scale, Tegner's activity scale, International Physical Activity Questionnaire, as well as measures of met expectations, overall improvement, and overall satisfaction. Total morphine equivalents (TMEs) were calculated from a regional prescription monitoring program. Eighty patients (41.7%) filled an opioid prescription preoperatively, and refill TMEs were significantly higher in this subpopulation. Opioid use was associated with unemployment, government insurance, smoking, depression, history of prior surgery, higher body mass index, greater comorbidities, and lower treatment expectations. Preoperative opioid use was associated with significantly worse 2-year scores on most PROs, including PROMIS physical function, pain interference, fatigue, social satisfaction, IKDC, NPS for the knee and rest of the body, and Marx's and Tegner's scales. There was a significant dose-dependent association between greater preoperative TMEs and worse scores for PROMIS physical function, pain interference, fatigue, social satisfaction, NPS body, and Marx's and Tegner's scales. Multivariable analysis confirmed that any preoperative opioid use, but not quantity of TMEs, was an independent predictor of worse 2-year scores for function, activity, and knee pain. Preoperative opioid use and TMEs were neither independent predictors of met expectations, satisfaction, patient-perceived improvement, nor improvement on any PROs. Our findings demonstrate that preoperative opioid use is associated with clinically relevant worse patient-reported knee function and pain after knee surgery.

Impact of Postoperative Opioid Use on 2-Year Patient-Reported Outcomes in Knee Surgery Patients.

The purposes of this study were to identify the patient characteristics associated with refilling a postoperative opioid prescription after knee surgery and to determine whether refilling opioids is associated with 2-year patient-reported outcomes. We hypothesized that postoperative refill of opioids would be associated with worse 2-year patient-reported outcomes. We studied 192 patients undergoing knee surgery at a single urban academic institution. Patients completed multiple patient-reported outcome measures preoperatively and 2 years postoperatively, including six Patient-Reported Outcomes Measurement Information System (PROMIS) domains, the International Knee Documentation Committee (IKDC) questionnaire, numeric pain scale scores for the operative knee and the rest of the body, Marx Activity Rating Scale, as well as measures of met expectations, improvement, and satisfaction. Total morphine equivalents (TMEs) were calculated from a regional prescription monitoring program. Patients who refilled a postoperative opioid prescription were compared with those who did not, and TMEs were calculated for those who refilled (Refill TMEs). One hundred twenty-nine patients (67%) refilled at least one postoperative opioid prescription. Black race, older age, higher average body mass index (BMI), smoking, greater medical comorbidities, preoperative opioid use, lower income, government insurance, and knee arthroplasty were associated with refilling opioids. Greater Refill TMEs was associated with black or white race, older age, higher average BMI, smoking, greater medical comorbidities, preoperative opioid use, government insurance, and unemployment. Refilling opioids and greater Refill TMEs were associated with worse postoperative scores on most patient-reported outcome measures 2 years after knee surgery. However, refilling opioids and greater Refill TMEs did not have a significant association with improvement after surgery. Multivariable analysis controlling for potential confounding variables confirmed that greater postoperative Refill TMEs independently predicted worse 2-year PROMIS Physical Function, 2-year PROMIS Pain Interference, and 2-year IKDC knee function scores. Postoperative refill of opioids was associated with worse 2-year patient-reported outcomes in a dose-dependent fashion. These findings reinforce the importance of counseling patients regarding opioid use and optimizing opioid-sparing pain management postoperatively.

Oxaliplatin disrupts pathological features of glioma cells and associated macrophages independent of apoptosis induction.

INTRODUCTION: Emerging evidence suggests that effective treatment of glioblastoma (GBM), the most common and deadly form of adult primary brain cancer, will likely require concurrent treatment of multiple aspects of tumor pathobiology to overcome tumor heterogeneity and the complex tumor-supporting microenvironment. Recent studies in non-central nervous system (CNS) tumor cells have demonstrated that oxaliplatin (OXA) can induce multi-faceted anti-tumor effects, in particular at drug concentrations below those required to induce apoptosis. These findings motivated re-investigation of OXA for the treatment of GBM. METHODS: The effects of OXA on murine KR158 and GL261 glioma cells including cell growth, cell death, inhibition of signal transducer and activator of transcription (STAT) activity, O-6-methylguanine-DNA methyltransferase (MGMT) expression, and immunogenic cell death (ICD) initiation, were evaluated by cytotoxicity assays, Western blot analysis, STAT3-luciferase reporter assays, qRT-PCR assays, and flow cytometry. Chemical inhibitors of endoplasmic reticulum (ER) stress were used to investigate the contribution of this cell damage response to the observed OXA effects. The effect of OXA on bone marrow-derived macrophages (BMDM) exposed to glioma conditioned media (GCM) was also analyzed by Western blot analysis. RESULTS: We identified the OXA concentration threshold for induction of apoptosis and from this determined the drug dose and treatment period for sub-cytotoxic treatments of glioma cells. Under these experimental conditions, OXA reduced STAT3 activity, reduced MGMT levels and increased temozolomide sensitivity. In addition, there was evidence of immunogenic cell death (elevated EIF2α phosphorylation and calreticulin exposure) following prolonged OXA treatment. Notably, inhibition of ER stress reversed the OXA-mediated inhibition of STAT3 activity and MGMT expression in the tumor cells. In BMDMs exposed to GCM, OXA also reduced levels of phosphorylated STAT3 and decreased expression of Arginase 1, an enzyme known to contribute to pro-tumor functions in the tumor-immune environment. CONCLUSIONS: OXA can induce notable multi-faceted biological effects in glioma cells and BMDMs at relatively low drug concentrations. These findings may have significant therapeutic relevance against GBM and warrant further investigation.

The synthetic neuroactive steroid SGE-516 reduces status epilepticus and neuronal cell death in a rat model of soman intoxication.

Organophosphorus nerve agents (OPNAs) are irreversible inhibitors of acetylcholinesterase that pose a serious threat to public health because of their use as chemical weapons. Exposure to high doses of OPNAs can dramatically potentiate cholinergic synaptic activity and cause status epilepticus (SE). Current standard of care for OPNA exposure involves treatment with cholinergic antagonists, oxime cholinesterase reactivators, and benzodiazepines. However, data from pre-clinical models suggest that OPNA-induced SE rapidly becomes refractory to benzodiazepines. Neuroactive steroids (NAS), such as allopregnanolone, retain anticonvulsant activity in rodent models of benzodiazepine-resistant SE, perhaps because they modulate a broader variety of GABAA receptor subtypes. SGE-516 is a novel, next generation NAS and a potent and selective GABAA receptor positive allosteric modulator (PAM). The present study first established that SGE-516 reduced electrographic seizures in the rat lithium-pilocarpine model of pharmacoresistant SE. Then the anticonvulsant activity of SGE-516 was investigated in the soman-intoxication model of OPNA-induced SE. SGE-516 (5.6, 7.5, and 10mg/kg, IP) significantly reduced electrographic seizure activity compared to control when administered 20min after SE onset. When 10mg/kg SGE-516 was administered 40min after SE onset, seizure activity was still significantly reduced compared to control. In addition, all cohorts of rats treated with SGE-516 exhibited significantly reduced neuronal cell death as measured by FluoroJade B immunohistochemistry. These data suggest synthetic NASs that positively modulate both synaptic and extrasynaptic GABAA receptors may be candidates for further study in the treatment of OPNA-induced SE.