Characterizing Trauma Patients with Delays in Orthopaedic Process Measures.

INTRODUCTION: Early operative intervention in orthopaedic injuries is associated with decreased morbidity and mortality. Relevant process measures (e.g. femoral shaft fixation <24 hours) are used in trauma quality improvement programs to evaluate performance. Currently, there is no mechanism to account for patients who are unable to undergo surgical intervention (i.e. physiologically unstable). We characterized the factors associated with patients who did not meet these orthopaedic process measures. METHODS: A retrospective cohort study of patients from 35 ACS-COT verified Level 1 and Level 2 trauma centers was performed utilizing quality collaborative data (2017-2022). Inclusion criteria were adult patients (≥18 years), ISS ≥5, and a closed femoral shaft or open tibial shaft fracture classified via the Abbreviated Injury Scale version 2005 (AIS2005). Relevant factors (e.g. physiologic) associated with a procedural delay >24 hours were identified through a multivariable logistic regression and the effect of delay on inpatient outcomes was assessed. A sub-analysis characterized the rate of delay in "healthy patients". RESULTS: We identified 5,199 patients with a femoral shaft fracture and 87.5% had a fixation procedure, of which 31.8% had a delay, and 47.1% of those delayed were "healthy." There were 1,291 patients with an open tibial shaft fracture, 92.2% had fixation, 50.5% had an irrigation and debridement and 11.2% and 18.7% were delayed, respectively. High ISS, older age and multiple medical comorbidities were associated with a delay in femur fixation, and those delayed had a higher incidence of complications. CONCLUSIONS: There is a substantial incidence of surgical delays in some orthopaedic trauma process measures that are predicted by certain patient characteristics, and this is associated with an increased rate of complications. Understanding these factors associated with a surgical delay, and effectively accounting for them, is key if these process measures are to be used appropriately in quality improvement programs. LEVEL OF EVIDENCE: Level III; Therapeutic/Care Management.

An Association Between Comorbidities and Postsurgical Complications in Adults Who Underwent Esophagectomy.

Background Esophagectomy is the surgical excision of part or all of the esophagus and is associated with both common and serious complications. Various comorbidities, such as diabetes mellitus, smoking, and congestive heart failure (CHF), have been detected in individuals who have undergone esophagectomy. This study investigates the association of baseline characteristics and comorbidities with postoperative complications. Methods A retrospective cohort study based on data from the National Surgical Quality Improvement Program database was conducted, evaluating 2,544 patients who underwent esophagectomy between January 2016 and December 2018. Data included baseline characteristics, established comorbidities, and postoperative complications within 30 days of the procedure. Risk-adjusted and unadjusted logistic regressions were used to assess the odds of postoperative complications against baseline characteristics. Results The majority of our population were white males (80.8% male; 78.2% white), with a mean age of 63.5 years. More than half of the patients were overweight or obese. A minority of our patients had a smoking history, weight loss, diabetes mellitus, chronic obstructive pulmonary disease (COPD), or CHF. The most frequent postoperative complications were as follows: return to the operating room (15.7%), anastomotic leak (12.9%), pneumonia (12.7%), bleeding/transfusions (11.8%), readmissions (11.4%), and unplanned intubation (10.5%). Adjusted associations for odds of experiencing a postoperative complication were found to be statistically significant for age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.03, and P < 0.001), operation time (OR 1.002, 95% CI 1.001-1.003, and P < 0.001), race (not white) (OR 1.76, 95% CI 1.26-2.47, and P = 0.001), BMI (underweight) (OR 2.18, 95% CI 1.36-3.50, and P = 0.001), smoking (OR 1.42, 95% CI 1.14-1.76, and P = 0.001), and chemotherapy and/or radiation (OR 0.82, 95% CI 0.68-0.99, P = 0.038). Conclusions Our study found that age, operation time, nonwhite race, underweight BMI, and smoking were independently associated with an increased risk of developing a postoperative complication following esophagectomy. Additionally, neoadjuvant chemotherapy and/or radiation are associated with a decreased risk. Understanding how baseline characteristics and comorbidities can affect rates of postoperative complications may help to adjust care for patients in both pre- and postoperative settings.

Prospective 5-year follow-up of L5-S1 versus L4-5 midline decompression and interspinous-interlaminar fixation as a stand-alone treatment for spinal stenosis compared with laminectomies.

Background: Spinal stenosis treatment includes laminectomies with or without fusion or with interspinous distraction with or without fixation. Lack of published data on interspinous fixation devices (IFD) at L5-S1 is less considered as an option due to the smaller anatomical S1 spinous process and the higher stresses from the immobile sacrum. Our objective was to evaluate the outcomes of an IFD used as a stand-alone treatment for spinal stenosis at L5-S1 and L4-5 compared to historical data on open laminectomies. Methods: Prospective comparative cohort study (Level 2) looking at collected preoperatively and postoperatively Visual Analog Scores (VAS) and Oswestry Disability Index (ODI) data, complications, and revision rates on 100 consecutive patients with spinal stenosis treated with midline decompression and InSpan (InSpan LLC, Malden, MA, USA) IFD, at L5-S1 and L4-5, up to five-year follow-up. All patients were treated by a single surgeon in an academic private practice. Historical published outcome data for open laminectomies were compared. Results: Among the 100 patients, 45 underwent surgery at L5-S1 with a mean VAS pain score that decreased by 75% and ODI improved by 63% (P<0.001). Fifty-five patients had surgery at L4-5 with mean VAS and ODI scores improved by 80% and 66% (P<0.001) respectively. Preoperative and postoperative ODI and preoperative VAS scores were similar at L5-S1 and L4-5, however, postoperative VAS scores were significantly less for L4-5 versus L5-S1 (P<0.01). All surgeries were completed in less than one hour. There was a total of one L4-5 revision (1.8%) and two L5-S1 revisions (4.4%). Comparable laminectomy data showed decrease in VAS and ODI scores by 51% and 62% (P<0.05). The reoperation rate for laminectomies at five to ten years varied up to 24%. Conclusions: Spinal stenosis patients treated with midline decompression and InSpan IFD, used as a stand-alone treatment for interspinous-interlaminar fixation, at L4-5 and L5-S1, showed improved outcome scores and low complication and revision rates at five years and were comparable to historical open laminectomy data. InSpan is a successful substitute for laminectomies in selected patients and was performed in less than 60 minutes. We recommend choosing the appropriately sized implant to achieve adequate distraction decompression to avoid recurrent symptoms.

Effectiveness of a Fully Impregnated Hydroxyapatite Polyetheretherketone Cage on Fusion in Anterior Cervical Spine Surgery.

Introduction Anterior cervical discectomy and fusion (ACDF) is the gold standard for the treatment of cervical spondylosis. However, new techniques, technologies, and improved implants have aided surgeons in reducing operative time with enhanced patient outcomes. Impregnated hydroxyapatite polyetheretherketone (HA PEEK) cages (Arena-C HA®, LESspine Inc. Malden, MA) are one such option that has aimed to increase the fusion rate. The authors herein aimed to assess the use of HA PEEK interbody cages by looking at outcomes, complications, and radiographic fusion.  Methods The medical records of 41 consecutive patients undergoing single-level ACDF with impregnated HA PEEK cages (group 1) were compared to the control group of 47 patients who had single-level ACDF without impregnated HA PEEK cages (group 2). Outcomes assessed included Visual Analog Scale (VAS) neck, Neck Disability Index (NDI) scores, radiographic fusion, and complication rates.  Results Of the 41 patients in group 1 (HA PEEK), 48% were female population with a mean age of 58.5+/- 1.7 years and BMI 29.7+/-1.2 kg/m2. Of the 47 patients in group 2 (non-HA PEEK), 53% were female with a mean age of 54.3+/- 1.2 years and BMI 27.8+/-0.8 kg/m2. Using t-test, there was a statistically significant intergroup difference in two-year VAS neck and NDI scores, p=0.007, and p=0.001, respectively. Radiographic fusion occurred as early as three months in the HA PEEK group.  Conclusions This study has demonstrated the equivalence of impregnated HA PEEK cages in single-level ACDF. Significant improvements were seen in VAS and NDI scores in the HA PEEK group. There was no incidence of heterotopic bone formation or reaction to HA PEEK cages. Additionally, a trend toward fusion was seen in HA PEEK patients as early as three to five months compared to seven to eight months for the ACDF group. We conclude that HA PEEK cages can be safely placed with excellent outcomes. However, further studies are required to look at added benefits.

Evaluation of global gene expression in regenerate tissues during Masquelet treatment.

The Masquelet induced-membrane (IM) technique is indicated for large segmental bone defects. Attributes of the IM and local milieu that contribute to graft-to-bone union are unknown. Using a rat model, we compared global gene expression profiles in critically sized femoral osteotomies managed using a cement spacer as per Masquelet to those left empty. At the end of the experiment, IM and bone adjacent to the spacer were collected from the Masquelet side. Nonunion tissue in the defect and bone next to the empty defect were collected from the contralateral side. Tissues were subjected to RNA isolation, sequencing, and differential expression analysis. Cell type enrichment analysis suggested the IM and the bone next to the polymethylmethacrylate (PMMA) spacer were comparatively enriched for osteoblastic genes. The nonunion environment was comparatively enriched for innate and adaptive immune cell markers, but only macrophages were evident in the Masquelet context. iPathwayGuide was utilized to identify cell signaling pathways and protein interaction networks enriched in the Masquelet environment. For IM vs nonunion false-discovery rate correction of P values rendered overall pathway differences nonsignificant, and so only protein interaction networks are presented. For the bone comparison, substantial enrichment of pathways and networks known to contribute to osteogenic mechanisms was revealed. Our results suggest that the PMMA spacer affects the cut bone ends that are in contact with it and at the same time induces the foreign body reaction and formation of the IM. B cells in the empty defect suggest a chronic inflammatory response to a large segmental osteotomy.

Design of biodegradable nanoparticles to modulate phenotypes of antigen-presenting cells for antigen-specific treatment of autoimmune disease.

Current therapeutic options for autoimmune diseases, such as multiple sclerosis (MS), often require lifelong treatment with immunosuppressive drugs, yet strategies for antigen-specific immunomodulation are emerging. Biodegradable particles loaded with disease-specific antigen, either alone or with immunomodulators, have been reported to ameliorate disease. Herein, we hypothesized that the carrier could impact polarization of the immune cells that associate with particles and the subsequent disease progression. Single injection of three polymeric carriers, 50:50 poly (DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly (DL-lactide) (PLA), loaded with the disease-specific antigen, proteolipid protein (PLP139-151), were investigated for the ability to attenuate clinical scores in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. At a low particle dose, mice treated with PLA-based particles had significantly lower clinical scores at the chronic stage of the disease over 200 days post immunization, while neither PLG-based particles nor OVA control particles reduced the clinical scores. Compared to PLG-based particles, PLA-based particles were largely associated with Kupffer cells and liver sinusoidal endothelial cells, which had a reduced co-stimulatory molecule expression that correlated with a reduction of CD4+ T-cell populations in the central nervous system. Delivery of PLA-based particles encapsulated with higher levels of PLP139-151 at a reduced dose were able to completely ameliorate EAE over 200 days along with inhibition of Th1 and Th17 polarization. Collectively, our study demonstrates that the carrier properties and antigen loading determine phenotypes of immune cells in the peripheral organs, influencing the amelioration of both acute and chronic stages of autoimmunity.

Designing drug-free biodegradable nanoparticles to modulate inflammatory monocytes and neutrophils for ameliorating inflammation.

Inflammation associated with autoimmune diseases and chronic injury is an initiating event that leads to tissue degeneration and dysfunction. Inflammatory monocytes and neutrophils systemically circulate and enter inflamed tissue, and pharmaceutical based targeting of these cells has not substantially improved outcomes and has had side effects. Herein, we investigated the design of drug-free biodegradable nanoparticles, notably without any active pharmaceutical ingredient or targeting ligand, that target circulating inflammatory monocytes and neutrophils in the vasculature to inhibit them from migrating into inflamed tissue. Nanoparticles were formed from 50:50 poly(DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly(DL-lactide) (PLA) (termed PLG-L, PLG-H, and PDLA, respectively) and were analyzed for their association with monocytes and neutrophils and their impact on disease course along with immune cell trafficking. For particles injected intravenously for 6 consecutive days to mice with experimental autoimmune encephalomyelitis (EAE), PLG-H particles had significantly lower EAE clinical scores than PBS control, while PLG-L and PDLA particles had modest or negligible effect on EAE onset. In vivo and in vitro data suggests that PLG-H particles had high association with immune cells, with preferential association with blood neutrophils relative to other particles. PLG-H particles restrained immune cells from the central nervous system (CNS), with increased accumulation in the spleen, which was not observed for mice receiving PDLA or control treatments. These results demonstrate that the particle composition influences the association with inflammatory monocytes and neutrophils in the vasculature, with the potential to redirect trafficking and ameliorate inflammation.