Rehabilitation Outcomes in Multiple Sclerosis Patients on Ocrelizumab Diagnosed With West Nile Virus Encephalitis.

Multiple sclerosis (MS) has a global prevalence exceeding two million people and is a leading cause of non-traumatic physical disability. MS can be treated with ocrelizumab, an anti-CD20 monoclonal antibody. West Nile virus (WNV) is the most common cause of mosquito-borne viral encephalitis in North America. It can lead to neuroinvasive WNV disease (WNND) affecting the brain and peripheral nervous system, especially in immunocompromised patients, such as those being treated with ocrelizumab for MS. WNND is exceedingly rare and reported in less than 1% of cases of WNV. It has been established that inpatient rehabilitation improves functional outcomes in patients with MS and those with WNND. However, the inpatient rehabilitation outcomes in patients diagnosed with both WNND and MS have not been reported. In this study, we aimed to examine the rehabilitation outcomes of MS patients on ocrelizumab diagnosed with WNND. We performed a retrospective chart review of patients with MS treated with ocrelizumab, who were diagnosed with WNND and admitted to a single facility. Rehabilitation outcomes were assessed using functional independence measure (FIM) scores on admission and discharge. Three patients met the inclusion criteria; two in acute rehab, and one in the long-term acute care hospital (LTACH). Both patients admitted to acute inpatient rehabilitation showed an improvement in FIM scores from admission to discharge, one patient from 9 to 16 and the other from 14 to 54. However, the patient admitted to the LTACH had no improvement in FIM score from admission to discharge. Patients admitted to acute rehab were ultimately discharged home, while the patient admitted to the LTACH required discharge to a subacute rehabilitation facility. Based on our findings, intense and prolonged comprehensive inpatient rehabilitation is associated with improved functional outcomes and increased likelihood of discharge to home in this population suffering from both central and peripheral nervous system involvement due to MS and WNND.

Preliminary study on the stabilization of varus proximal femoral osteotomies using pediatric LCP plates in adults undergoing combined correction of proximal femoral and acetabular dysplasia.

PURPOSE: Proximal femoral osteotomy (PFO) with periacetabular osteotomy (PAO) improves femoral head coverage in patients with proximal femoral and acetabular dysplasia. Historically, blade plates used in the PFO cause soft-tissue irritation and often lead to implant removal. Here we present a technique using a lower profile pediatric proximal femoral locking compression plate (LCP) for the PFO in a series of adults. METHODS: The results from 13 hips in 11 patients ≥ 18 years old (age 18-37) with > 10 months of follow-up are presented. RESULTS: All patients had improved radiographic parameters, pain, and total Merle d'Aubigné-Postel scores postoperatively. Eleven hips (85%) had the LCP removed an average of 15.8 ± 8.6 months postoperatively, often due to pain over the greater trochanter. CONCLUSION: The pediatric proximal femoral LCP is effective for PFO in combined PAO PFO procedures but has a high rate of lateral hip discomfort leading to implant removal.

Incisional negative pressure wound therapy may not protect against post-operative surgical site complications in bicondylar tibial plateau fractures.

PURPOSE: To determine if incisional negative pressure wound therapy is protective against post-operative surgical site complications following definitive fixation of bicondylar tibial plateau fractures. METHODS: A retrospective analysis of patients diagnosed with an acute bicondylar tibial plateau fracture (AO/OTA 41-C) undergoing ORIF from 2010 to 2020 was performed. Patients received either a standard sterile dressing (SD) or incisional negative pressure wound therapy (iNPWT). Primary outcomes included surgical site infection, osteomyelitis, and wound dehiscence. Secondary outcomes included non-union and return to the operating room. Multivariate logistic regression analyses were performed. RESULTS: 180 patients were included and 22% received iNPWT (n = 40) and 78% received standard dressings (n = 140). iNPWT was more common in active smokers (24.7% vs. 19.3%, p = 0.002) and the SD group was more likely to be lost to follow up (3.6% vs. 0%, p = 0.025). iNPWT was not protective against infection or surgical site complications, and in fact, was associated with higher odds of post-operative infection (OR: 8.96, p = 0.005) and surgical site complications (OR:4.874, p = 0.009) overall. Alcohol abuse (OR: 19, p = 0.005), tobacco use (OR: 4.67, p = 0.009), and time to definitive surgery (OR = 1.21, p = 0.033) were all independent risk factors for post-operative infection. CONCLUSION: In this series of operatively treated bicondylar tibial plateau fractures, iNPWT did not protect against post-operative surgical site complications compared to conventional dressings. Tobacco use, alcohol abuse, and time to definitive surgery, were independent risk factors for post-operative infection. Further studies are needed to determine if iNPWT offers a protective benefit in exclusively high-risk patients with relevant medical and social history.

A High Separation Factor for 165Er from Ho for Targeted Radionuclide Therapy.

Background: Radionuclides emitting Auger electrons (AEs) with low (0.02-50 keV) energy, short (0.0007-40 µm) range, and high (1-10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide 177Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce 165Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Methods: Biomedical cyclotrons proton-irradiated spot-welded Ho(m) targets to produce 165Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200-400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20-50 µm, 1.3 mL) and bDGA (50-100 µm, 0.2 mL) extraction chromatography. The purified 165Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [165Er]PSMA-617. Results: Irradiation of 80-180 mg natHo targets with 40 µA of 11-12.5 MeV protons produced 165Er at 20-30 MBq·µA-1·h-1. The 4.9 ± 0.7 h radiochemical isolation yielded 165Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% and a Ho/165Er separation factor of (2.8 ± 1.1) · 105. Radiolabeling experiments synthesized [165Er]PSMA-617 at DC molar activities of 37-130 GBq·µmol-1. Conclusions: A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [165Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer.

Fate of the Uninsured Ankle Fracture: Significant Delays in Treatment Result in an Increased Risk of Surgical Site Infection.

OBJECTIVE: To examine the impact of insurance status on access to orthopaedic care and incidence of surgical site complications in patients with closed unstable ankle fractures. DESIGN: Retrospective chart review. SETTING: Certified Level-1 urban trauma center and county facility. PARTICIPANTS: Four hundred eighty-nine patients with closed unstable ankle fractures undergoing open reduction and internal fixation between 2014 and 2016. INTERVENTION: Open reduction and internal fixation of unstable ankle fracture. MAIN OUTCOME MEASURES: Time from injury to presentation, time from injury to surgery, rate of surgical site infections, and loss to follow-up. RESULTS: A total of 489 patients (70.5% uninsured vs. 29.5% insured) were enrolled. Uninsured patients were more likely to be present to an outside hospital first (P = 0.004). Time from injury to presentation at our hospital was significantly longer in uninsured patients (4.5 ± 7.6 days vs. 2.3 ± 5.5 days, P < 0.001). Time from injury to surgery was significantly longer in uninsured patient (9.4 ± 8.5 days vs. 7.3 ± 9.1 days, P < 0.001). Uninsured patients were more likely to be lost to postoperative follow-up care (P = 0.002). A logistic regression analysis demonstrated that delayed surgical timing was directly associated with an increased risk of postoperative surgical site infection (P = 0.002). CONCLUSIONS: Uninsured patients with ankle fractures requiring surgery experience significant barriers regarding access to health care. Delay of surgical management significantly increases the risk of surgical site infections in closed unstable ankle fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Antegrade Elastic Intramedullary Nailing Insertion Technique Results in Higher Incidence of Symptomatic Implants in Pediatric Ulnar Fractures.

Retrograde and antegrade nailing techniques are the two options available to a surgeon when using elastic stable intramedullary nailing; however, the literature comparing these two nailing techniques is scarce. Thus, we conducted a retrospective review of all pediatric and adolescent ulnar fractures treated with elastic stable intramedullary nailing at our facility. We hypothesize that the clinical outcomes (implant and wound complications) and the time between surgery and radiographic union will be similar for both techniques. Methods: A retrospective chart review of pediatric ulnar fracture patients treated at our facility was performed. Demographic and health information associated with the injury were collected, and the clinical outcomes of the two techniques were compared. Results: A total of 53 patients with 54 fractures were included in this study. Antegrade nail insertion was used to treat 59.2% fractures. Radiographic union was achieved in all patients. Nail insertion technique was not associated with postoperative wound complications, time to radiographic union or implant removal, or significant deficits in upper extremity rotation (P > 0.05). Antegrade nailing resulted in a symptomatic implantation 3.97 times more frequently than compared with retrograde nailing (P = 0.036). Discussion: Antegrade nailing demonstrates a similar healing profile but higher implant complications compared with the retrograde nailing technique in pediatric ulnar fractures.

The gut microbiome distinguishes mortality in trauma patients upon admission to the emergency department.

BACKGROUND: Traumatic injury can lead to a compromised intestinal epithelial barrier, decreased gut perfusion, and inflammation. While recent studies indicate that the gut microbiome (GM) is altered early following traumatic injury, the impact of GM changes on clinical outcomes remains unknown. Our objective of this follow-up study was to determine if the GM is associated with clinical outcomes in critically injured patients. METHODS: We conducted a prospective, observational study in adult patients (N = 67) sustaining severe injury admitted to a level I trauma center. Fecal specimens were collected on admission to the emergency department, and microbial DNA from all samples was analyzed using the Quantitative Insights Into Microbial Ecology pipeline and compared against the Greengenes database. α-Diversity and ß-diversity were estimated using the observed species metrics and analyzed with t tests and permutational analysis of variance for overall significance, with post hoc pairwise analyses. RESULTS: Our patient population consisted of 63% males with a mean age of 44 years. Seventy-eight percent of the patients suffered blunt trauma with 22% undergoing penetrating injuries. The mean body mass index was 26.9 kg/m. Significant differences in admission ß-diversity were noted by hospital length of stay, intensive care unit hospital length of stay, number of days on the ventilator, infections, and acute respiratory distress syndrome (p < 0.05). ß-Diversity on admission differed in patients who died compared with patients who lived (mean time to death, 8 days). There were also significantly less operational taxonomic units in samples from patients who died versus those who survived. A number of species were enriched in the GM of injured patients who died, which included some traditionally probiotic species such as Akkermansia muciniphilia, Oxalobacter formigenes, and Eubacterium biforme (p < 0.05). CONCLUSION: Gut microbiome diversity on admission in severely injured patients is predictive of a variety of clinically important outcomes. While our study does not address causality, the GM of trauma patients may provide valuable diagnostic and therapeutic targets for the care of injured patients. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Impact of Insurance Status on Time to Evaluation and Treatment of Meniscal Tears in Children, Adolescents, and College-Aged Patients in the United States.

BACKGROUND: The meniscus is vital for load bearing, knee stabilization, and shock absorption, making a meniscal tear a well-recognized sport-related injury in children and young adults. An inverse relationship between the quality and value of orthopaedic care provided and the overall treatment cycle exists in which delayed meniscal tear treatment increases the likelihood of unfavorable outcomes. Although a majority of children and young adults have health insurance, many athletes within this demographic still face significant barriers in accessing orthopaedic services because of insurance type and household income. PURPOSE: To determine the impact of insurance status and socioeconomic markers on the time to orthopaedic evaluation and treatment as well as the rate of surgical interventions for meniscal tears in children and young adult athletes in the United States. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We conducted a retrospective review of all patients ≤22 years of age who presented to our institution between 2008 and 2016 and who were diagnosed with meniscal tears. Patients were categorized based on insurance and socioeconomic status. Dates of injury, referral, evaluation by an orthopaedic surgeon, and surgery were also recorded. Chi-square and regression analyses were utilized to determine the significance and correlation between the influencing factors and time to referral, evaluation, and surgery. RESULTS: Publicly insured, commercially insured, and uninsured patients comprised 49.4%, 26.6%, and 24.1%, respectively, of the 237 patients included in this study. Insurance status was predictive of time to orthopaedic referral, initial evaluation, and surgery (P < .01). Uninsured and publicly insured patients experienced significant delays during their orthopaedic care compared with commercially insured patients. However, no correlation was found between insurance status or household income and the rate of surgical interventions. CONCLUSION: Publicly insured and uninsured pediatric and college-aged patients faced significant barriers in accessing orthopaedic services, as demonstrated by substantially longer times between the initial injury and referral to an orthopaedic evaluation and surgery; however, these socioeconomic factors did not affect the rate of surgical management. Clinical competency regarding the effects of socioeconomic factors on the time to orthopaedic care and efforts to expedite care among underinsured and underserved children are vital for improving patient outcomes.

A prospective study in severely injured patients reveals an altered gut microbiome is associated with transfusion volume.

BACKGROUND: Traumatic injury can lead to a compromised intestinal epithelial barrier and inflammation. While alterations in the gut microbiome of critically injured patients may influence clinical outcomes, the impact of trauma on gut microbial composition is unknown. Our objective was to determine if the gut microbiome is altered in severely injured patients and begin to characterize changes in the gut microbiome due to time and therapeutic intervention. METHODS: We conducted a prospective, observational study in adult patients (n = 72) sustaining severe injury admitted to a Level I Trauma Center. Healthy volunteers (n = 13) were also examined. Fecal specimens were collected on admission to the emergency department and at 3, 7, 10, and 13 days (±2 days) following injury. Microbial DNA was isolated for 16s rRNA sequencing, and α and ß diversities were estimated, according to taxonomic classification against the Greengenes database. RESULTS: The gut microbiome of trauma patients was altered on admission (i.e., within 30 minutes following injury) compared to healthy volunteers. Patients with an unchanged gut microbiome on admission were transfused more RBCs than those with an altered gut microbiome (p < 0.001). Although the gut microbiome started to return to a ß-diversity profile similar to that of healthy volunteers over time, it remained different from healthy controls. Alternatively, α diversity initially increased postinjury, but subsequently decreased during the hospitalization. Injured patients on admission had a decreased abundance of traditionally beneficial microbial phyla (e.g., Firmicutes) with a concomitant decrease in opportunistic phyla (e.g., Proteobacteria) compared to healthy controls (p < 0.05). Large amounts of blood products and RBCs were both associated with higher α diversity (p < 0.001) and a ß diversity clustering closer to healthy controls. CONCLUSION: The human gut microbiome changes early after trauma and may be aided by early massive transfusion. Ultimately, the gut microbiome of trauma patients may provide valuable diagnostic and therapeutic insight for the improvement of outcomes postinjury. LEVEL OF EVIDENCE: Prognostic and Epidemiological, level III.

The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing.

The ecological community of microorganisms in/on humans, termed the microbiome, is vital for sustaining homeostasis. While culture-independent techniques have revealed the role of the gut microbiome in human health and disease, the role of the cutaneous microbiome in wound healing is less defined. Skin commensals are essential in the maintenance of the epithelial barrier function, regulation of the host immune system, and protection from invading pathogenic microorganisms. In this review, we summarize the literature derived from pre-clinical and clinical studies on how changes in the microbiome of various acute and chronic skin wounds impact wound healing tissue regeneration. Furthermore, we review the mechanistic insights garnered from model wound healing systems. Finally, in the face of growing concern about antibiotic-resistance, we will discuss alternative strategies for the treatment of infected wounds to improve wound healing and outcomes. Taken together, it has become apparent that commensals, symbionts, and pathogens on human skin have an intimate role in the inflammatory response that highlights several potential strategies to treat infected, non-healing wounds. Despite these promising results, there are some contradictory and controversial findings from existing studies and more research is needed to define the role of the human skin microbiome in acute and chronic wound healing.