Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-derived Xenograft Mouse Model.

Chimeric antigen receptor T (CART) cell therapy has emerged as a powerful tool for the treatment of multiple types of CD19+ malignancies, which has led to the recent FDA approval of several CD19-targeted CART (CART19) cell therapies. However, CART cell therapy is associated with a unique set of toxicities that carry their own morbidity and mortality. This includes cytokine release syndrome (CRS) and neuroinflammation (NI). The use of preclinical mouse models has been crucial in the research and development of CART technology for assessing both CART efficacy and CART toxicity. The available preclinical models to test this adoptive cellular immunotherapy include syngeneic, xenograft, transgenic, and humanized mouse models. There is no single model that seamlessly mirrors the human immune system, and each model has strengths and weaknesses. This methods paper aims to describe a patient-derived xenograft model using leukemic blasts from patients with acute lymphoblastic leukemia as a strategy to assess CART19-associated toxicities, CRS, and NI. This model has been shown to recapitulate CART19-associated toxicities as well as therapeutic efficacy as seen in the clinic.

Primary total hip arthroplasty complications and costs in liver transplant recipients: a matched analysis using a national database.

BACKGROUND: The number of liver transplant recipients (LTR) is worldwide increasing and, as the survival is improving as well, there is an increasing number of patients needing total hip arthroplasty (THA). There might be increased risks for this specific group of patients and due to their comorbidities costs might be higher too. Using a big national database outcome and cost of THA should be compared between liver transplant recipients and the general population. METHODS: The study was performed using a collection of Medicare, Medicaid, and private insurance claims. Length of stay (LOS), 30-day readmissions, complications rates up to 5 years, and 90-day total cost of care between liver transplant recipients and matched non-transplant patients should be compared. All primary THAs from 2010 to 2019 were identified. 513 patients with a liver transplant before their THA were matched to 10,759 patients without a history of solid organ transplant at a 1:20 ratio based on age, sex, Charlson Comorbidity Index, obesity, and diabetes status. RESULTS: LTR had a longer average LOS (4.2 vs. 3.4 days, p < 0.001). There was no difference in the thirty-day readmissions (5.7% vs. 4.1%, p = 0.117) and 90-day dislocation rates (2.9% vs. 2.4%, p = 0.600). Total costs in the first ninety days after THA were not different between the LTR and controls (p = 0.756). CONCLUSIONS: These findings suggest that complications and costs are no major point of concern in patients with liver transplant that are operated with THA.

Assessment of Staphylococcal Clinical Isolates from Periprosthetic Joint Infections for Potential Bacteriophage Therapy.

BACKGROUND: Bacteriophage therapy is a potential adjunctive treatment for periprosthetic joint infections (PJIs) given the capabilities of bacteriophages to degrade biofilms, self-replicate, and lyse bacteria. However, many aspects of this therapeutic are ill-defined, and the narrow spectrum of bacteriophage activity along with limited available bacteriophage strains curb potential use for specific bacteria such as Staphylococcus aureus at the present time. Therefore, the aim of this study was to determine the feasibility of using bacteriophages for PJI by (1) categorizing the causative organisms in hip and knee PJI at a tertiary academic center and (2) evaluating in vitro activity of a group of bacteriophages against clinical S. aureus PJI isolates. METHODS: Patients with chronic hip or knee PJI after undergoing the first stage of a 2-stage revision protocol from 2017 to 2020 were identified retrospectively by a query of the hospital billing database. The causative pathogens in 129 cases were reviewed and categorized. From this cohort, preserved S. aureus isolates were tested against a library of 15 staphylococcal bacteriophages to evaluate for bacterial growth inhibition over 48 hours. RESULTS: S. aureus was the most common pathogen causing PJI (26% [33] of 129 cases). Of 29 S. aureus samples that were analyzed for bacteriophage activity, 97% showed adequate growth inhibition of the predominant planktonic colonies by at least 1 bacteriophage strain. However, 24% of the 29 samples demonstrated additional smaller, slower-growing S. aureus colonies, none of which had adequate growth inhibition by any of the initial 14 bacteriophages. Of 5 secondary colonies that underwent subsequent testing with another bacteriophage with enhanced biofilm activity, 4 showed adequate growth inhibition. CONCLUSIONS: Effective bacteriophage therapeutics are potentially available for S. aureus PJI isolates. The differences in bacteriophage activity against the presumed small-colony variants compared with the planktonic isolates have important clinical implications. This finding suggests that bacteriophage attachment receptors differ between the different bacterial morphologic states, and supports future in vitro testing of bacteriophage therapeutics against both planktonic and stationary states of PJI clinical isolates to ensure activity.

Cost analysis of ankle syndesmosis internal fixation.

BACKGROUND: Unstable ankle syndesmosis injuries are common, and the optimal surgical fixation is controversial. The two main options for stabilization of syndesmotic injuries are suture button fixation and screw fixation. Suture button fixation has a higher initial cost, but may have a lower hardware removal rate. The purpose of this study was to compare the costs of syndesmotic fixation. METHODS: A cost analysis was performed at a single university-affiliated hospital. Variables included the number of suture buttons, the number and type of syndesmosis screws used, and the frequency of hardware removal and operative time required for hardware removal. There were four clinical scenarios evaluated: (A) one suture button versus one cortical screw; (B) two suture buttons versus two cortical screws; (C) one suture button versus one locking screw; (D) two suture buttons versus two locking screws. Suture button removal rate was assumed to be 0% in the analysis. RESULTS: Cost equivalence was achieved at an 18 to 53% syndesmotic screw removal rate depending on the fixation construct used and the amount of time required for hardware removal. When the syndesmosis screws were removed 100% of the time, suture button fixation was more economical by $85,000-$194,656 per 100 ankles. When hardware was never removed, suture button fixation was more expensive by $169,844-$295,500 per 100 ankles. CONCLUSION: This study demonstrates that the costs associated with syndesmosis fixation are more dependent on the rate of hardware removal than the type of hardware utilized. Routine removal of syndesmosis screws is clearly less economical than suture button fixation.

Assessment of Splints Applied for Pediatric Fractures in an Emergency Department/Urgent Care Environment.

BACKGROUND: Fractures are common in the pediatric population. The initial evaluation is rarely by an orthopaedic surgeon, but commonly an emergency room or urgent care center physician/extender. This typically involves splint application by a nonorthopaedist to immobilize the extremity and provide stabilization. Iatrogenic injuries from inappropriate splint placement are a potential public health and legal concern that can lead to complications. The primary purpose of this study was to prospectively evaluate the adequacy of all splints placed on patients who presented to a pediatric orthopaedic office; secondary outcomes included assessing prevalence and types of complications that were associated with inadequate splints. METHODS: Patients aged 0 to 18 years who presented with a splint were prospectively enrolled. Information was obtained regarding demographics of the patient and splint placement. Splints were evaluated for functional position, appropriate length, and presence of elastic bandage on the skin. Photographs were taken of each splint, and the extremity was examined for any soft tissue complications. Splints were not removed in 31 patients who had undergone fracture reduction. RESULTS: In total, 275 patients were prospectively enrolled. Splints were improperly placed in 93%, with application of elastic bandage directly to the skin accounting for 77%. Improper positioning was observed in 59%, and inappropriate splint length was present in 52%. Skin and soft tissue complications were observed in 40%. The most common iatrogenic splint-related complication was excessive edema, seen in 28%. Direct injury to the skin and soft tissue was seen in 6%. CONCLUSIONS: Many practitioners incorrectly apply splints, potentially leading to suboptimal results or causing injury. Complications of poor splint placement include excessive swelling, skin breakdown, and poor immobilization. Health care workers who treat pediatric fractures may benefit from more extensive education regarding proper splinting techniques. LEVEL OF EVIDENCE: Level 2-therapeutic study.

Upper extremity injuries in motorcyclists: Implications for mortality and need for rehabilitation services.

BACKGROUND: Motorcycle crashes (MCCs) constitute a disproportionately high number of road accidents that result in mortality and injury, compared with other motor vehicle collisions. Distribution and characteristics of upper extremity injuries sustained by motorcyclists and their implications are not well established. We sought to determine the epidemiology of upper extremity injuries in motorcyclists and the independent effects of the injuries on mortality and need for rehabilitative services. METHODS: All motorcyclist admissions at our Level I trauma center from 2006 through 2010 were retrospectively reviewed. We identified and categorized all upper extremity injuries. Demographic data, in-hospital mortality, disposition to a rehabilitation facility, and other potential confounding covariates were recorded. Propensity score-adjusted logistic regression models quantified the effects of upper limb injuries on mortality and transfer to rehabilitation facilities. RESULTS: Thirty-five percent (759 of 2,151 patients) involved in MCCs sustained upper extremity injury. Shoulder girdle injuries were most common (n = 433), followed by forearm fractures (n = 272). Mortality rate was 4% (87 of 2,151 patients) for all MCC admissions. Propensity score-adjusted logistic regression models showed that injuries distal to the humerus had an independent odds ratio for mortality of 0.41 (95% confidence interval, 0.21-0.8). Odds of requiring rehabilitation after discharge were 1.82 times (95% confidence interval, 1.47-2.26) higher when any upper extremity injury was sustained. CONCLUSION: Upper extremity injuries are common in MCCs. Distal injuries are associated with lower mortality rates possibly because of a "crumple zone effect" of distal upper extremities sparing the head and neck region from direct impact in head-first injuries. MCC patients with upper extremity injuries are more likely to require rehabilitation services. LEVEL OF EVIDENCE: Epidemiologic study, level III.

The economic impact of periprosthetic infections following total knee arthroplasty at a specialized tertiary-care center.

The purpose of this study was to measure the impact of periprosthetic joint infections (PJIs) on the length of hospitalization, readmissions, and the associated costs. Between 2007 and 2011, our prospectively collected infection database was reviewed to identify PJIs that occurred following primary total knee arthroplasty (TKA), which required a two-stage revision. We identified 21 consecutive patients and matched them to 21 non-infected patients who underwent uncomplicated primary TKA. The patients who had PJIs had significantly longer hospitalizations (5.3 vs. 3.0 days), more readmissions (3.6 vs. 0.1), and more clinic visits (6.5 vs. 1.3) when compared to the matched group, respectively. The mean annual cost was significantly higher in the infected cohort ($116,383; range, $44,416 to $269,914) when compared to the matched group ($28,249; range, $20,454 to $47,957). Periprosthetic infections following TKA represent a tremendous economic burden for tertiary-care centers and to patients.

Economic evaluation of chlorhexidine cloths on healthcare costs due to surgical site infections following total knee arthroplasty.

The purpose of this study was to evaluate the overall annual healthcare cost savings of adding a pre-operative chlorhexidine cloth preparation protocol. We used reports from the National Healthcare Safety Network and previously published reports to determine a range of surgical site infection rates following total knee arthroplasty and the cost per revision procedure. The savings listed are potential, but may be less. The cost benefit of using chlorhexidine at our institution per 1,000 total knee arthroplasty patients was a net savings of approximately $2.1 million. The annual healthcare savings ranged from $0.78 to $3.18 billion. This epidemiologic evaluation of using chlorhexidine prior to undergoing total knee arthroplasty has demonstrated the potential to decrease healthcare costs primarily by decreasing the incidence of surgical site infections.

Single-use cutting blocks and trials lower costs in primary total knee arthroplasty.

Because total knee arthroplasty is one of the most common orthopaedic procedures, it is important that the medical community continually strive for cost reductions. This prospective controlled trial aimed to determine if cost decreases could be achieved in non-navigated and navigated procedures by replacing traditional saws, cutting blocks, and trials with a specialized single-use system. Costs were lowered by an estimated $140.00-220.00 per surgery as a result of fewer instrument trays being reprocessed, and an estimated $75.00-330.00 per instrument case due to a 10-24-minute time savings during tray rewrapping. This study has positive financial implications for patients, hospitals, institutions, and third-party carriers.

Assessment of static progressive stretch for the treatment of shoulder stiffness: a prospective case series.

INTRODUCTION: The purpose of this study was to evaluate the use of a patient-directed static progressive stretch orthosis for the treatment of shoulder stiffness. METHODS: Twenty-three patients who had limitations in range of motion of the shoulder and who had failed conventional physical therapy methods were studied. This cohort included 15 women and 8 men with a mean age of 53 years. Treatment comprised one to three 30- to 60-minute sessions per day with a patient-controlled orthosis utilizing static progressive stretch. The patients adjusted the degree of stretch at 5-minute intervals as tolerated. Compliance, range of motion, patient satisfaction, and complications were assessed, and a two-way repeated measure ANOVA was performed to assess the effects of age or gender. RESULTS: After a mean treatment duration of 10 weeks (range, 4 to 19 weeks), the patients gained a mean of 22° (range, -47 to 57°) of external rotation, 18° (range, -19 to 55°) of internal rotation, 46° (range, 3 to 97°) of abduction, and 23° (range, 3 to 40°) of forward flexion. In total, 22 of 23 patients (96%) experienced increases in range of motion that were maintained at 1 year following treatment. Statistically significant increases in range of motion and clinical function scores were noted; age and gender did not appear to influence the outcomes. DISCUSSION: This device compared favorably to other treatment methods for shoulder stiffness. An orthosis utilizing static progressive stretch was a useful adjunct for the treatment of shoulder stiffness refractory to conventional therapy.

DVT prophylaxis: better living through chemistry: opposes.

The association between total hip arthroplasty and subsequent postoperative deep venous thrombosis is of particular concern because it can lead to symptomatic venous thromboembolic events. However, controversy remains about the optimal approach to prophylaxis. Some authors recommend the use of various chemoprophylactic agents, while others advocate the use of mechanical devices or combinations. The ideal method of prophylaxis should be effective and easy to administer, have a predictable onset and duration, have minimal interaction with food or other drugs, be easily reversible, be cost effective, and have a low risk of side effects. While available chemoprophylactic agents address some of these attributes, all have substantial drawbacks. Among the most concerning effects for orthopedic surgeons is the increased risk of bleeding and hematoma formation, which can be associated with periprosthetic infections. These typically lead to additional surgical procedures and significant patient morbidity, and can adversely impact clinical outcomes. An alternative to chemoprophylaxis is the use of pneumatic intermittent compression devices. Modern compression devices are portable and easy to use, and have a high rate of patient compliance. Several studies have demonstrated the efficacy of these devices in reducing the risk of symptomatic venous thromboembolic disease, in some cases resulting in lower mortality when compared to pharmacological agents. Additionally, these devices significantly reduce the risk of postoperative bleeding.

Preoperative chlorhexidine preparation and the incidence of surgical site infections after hip arthroplasty.

The purpose of this study was to evaluate effectiveness of an advance, at-home chlorhexidine-impregnated skin preparation cloth in decreasing the incidence of deep periprosthetic hip arthroplasty infections. Arthroplasty surgeons at the senior author's institution provided their patients with chlorhexidine-impregnated single-use cloths for use at home the night before and the morning of surgery. Between January 2007 and December 2009, the compliance of this practice, as well as the incidence of periprosthetic infections, was monitored for all patients who underwent hip arthroplasty. Of the 1134 patients who underwent hip arthroplasty, 157 patients completely complied with the preoperative chlorhexidine preparation protocol. There were 14 infections in the group that was not compliant (1.6% infection rate), and there were no infections in the compliant patient population. Based on the results of this study, at-home preoperative patient skin preparation appears to be a simple and cost-effective method to reduce periprosthetic hip infection rates.