Acetabular Fracture Outcomes and Complications: An International Comparison.

Introduction: Despite the groundbreaking research by Judet and Letournel in the 1960s, the specific equipment, surgical approach, fixation strategy, and post-operative course for treating acetabular fractures have not been standardized. Therefore, this study aimed to compare technological resources, operative procedures, and post-operative complications between patients treated for acetabular fractures in Romania and the United States (U.S.). Methods: Between February 2011 and August 2018, a total of 116 Romanian patients and 373 U.S. patients underwent open reduction and internal fixation for acetabular fractures. Data were collected prospectively for Romania and retrospectively for the U.S. The authors used T-tests, Fisher's exact tests, and odds ratios to analyze categorical data while ordinal date were assessed using logistic regression. Results: U.S. patients had higher comorbidity rates for diabetes, obesity, and hypertension. However, the initial quality of reduction, graded with Matta's criteria, was similar between American and Romanian patients. Post-operatively, U.S. patients had significantly higher Brooker criteria scores for heterotopic ossification. Rates of deep vein thrombosis, infections, sciatic nerve lesions, and loss of reduction between the two countries were not significantly different. Conclusions: Given the similar initial reduction quality despite technological differences, the authors suggest that fundamental factors, such as surgeon training and experience, may have a greater impact than the availability of technologically advanced operative resources. Future research focusing on the efficacy of these advanced resources for acetabular fracture fixation could help determine their true impact on patient outcomes and improve the cost-effectiveness of this surgery.

A Brief Review of the Literature for Published Dual-Energy X-Ray Absorptiometry Protocols for Athletes.

CONTEXT: Dual-energy x-ray absorptiometry (DXA) is widely known for its utility in diagnosing a patient with osteopenia or osteoporosis; however, its utility in evaluation of body composition and potential athletic performance was previously routinely overlooked. In recent years, athletic programs have begun employing this equipment during athlete screening. However, it is currently unknown how athletic programs are utilizing this information to guide an athlete's training and health. OBJECTIVE: To explore the literature to identify what is known regarding sports performance and athlete health based on body composition recordings. DATA SOURCES: PubMed and Google Scholar databases were searched for this brief review. STUDY SELECTION: A focus was placed on articles within the past 10 years that discussed DXA protocols within athletic populations; 14 articles were included in this brief literature review. STUDY DESIGN: Brief literature review. LEVEL OF EVIDENCE: Level 5. DATA EXTRACTION: One member of the research team searched the literature and retrieved articles with the purpose of analyzing and/or explaining DXA imaging in body composition analysis of active persons (primarily athletes). RESULTS: Quality assurance scans with a phantom calibration block as well as athlete prescreening condition and activity standardization was routinely recommended. However, only 1 study reported a specific DXA protocol for athletes, and only 1 study described guidelines for how to report DXA results in athletic populations, suggesting it is plausible yet difficult due to the small changes detectable. CONCLUSION: Due to the limited literature as well as a lack of reference values for specific athletic populations, the authors of this review recommend using the current Nana et al (Int J Sport Nutr Exerc Metab 2015;25:198-215) DXA protocol for performing DXA scans in the athletic population as well as current Hind et al (J Clin Densitom 2018;21:429-443) guidelines for distributing the information.

A Scoping Review to Assess Risk of Fracture Associated with Anxiolytic Medications.

Introduction: Recent research has focused on evaluating the impact of pharmalogical sources on fracture risk. The purpose of this study was to review the literature on anxiolytic medications that may be associated with an increased risk of fracture. Methods: A search was conducted in MEDLINE and Embase databases to identify primary clinical studies of patients who sustained a fracture while prescribed anxiolytic medications and were published prior to July 2021. Anxiolytics defined by ATC Class N05B, beta blockers, and zolpidem were included. The search terms consisted of variations of the following: ("Psychotropic Drugs" or MeSH terms) AND ("Fracture" or MeSH terms). Results: Of 3,213 studies, 13 (0.4%) met inclusion criteria and were evaluated. Fractures associated with benzodiazepine were reported in 12 of 13 studies; the highest risk occurred in patients aged 60 years and older (RR=2.29, 95% CI (1.48-4.40)). The ATC Class N05B showed an increased fracture risk for those ≤ 55 years of age that differed by sex: for men (RR=5.42, 95% CI(4.86-6.05)) and for women (RR=3.33, 95% CI (3.03-3.66)). Zolpidem also showed an increase fracture risk (RR=2.29, 95% CI(1.48-3.56)), but only during the first four weeks of treatment. A relative risk of 0.77, 95% CI(0.72-0.83) was observed for beta blockers. Conclusions: Fractures are a mainstay of traumatic injuries and are accompanied by economical, physiological, and psychological hardship. With proper assessment and prophylactic measures, fracture risk can be reduced dramatically. Anxiolytic medications have been described widely to increase fracture risk, such as benzodiazepines in 60+ year old patients, and ATC Class N05B anxiolytics increased fracture risk in 55+ year old men and in 55+ year old women. Yet, some studies showed that at low doses, nitrazepam lowered fracture risk. Other anxiolytic medications, such as zolpidem and beta blockers, also showed a decrease in fracture risk. Ultimately, this scoping review helped to illuminate the inconsistency of anxiolytic fracture risk assessment while simultaneously illustrating the necessary steps to guide future research.

Bone Health in the Transgender Population.

¼ Transgender women are more susceptible to low bone mineral density (BMD) before initiating gender-affirming hormone therapy (GAHT), and while bone density initially improves with GAHT, it gradually declines while still remaining above baseline. Transgender women older than 50 years have a comparable fracture risk as age-matched cisgender women. Transgender men typically have normal or increased BMD before initiating and while receiving GAHT and are not at increased risk of fractures.¼ Transgender youth who receive puberty-blocking medications experience either no change or a slight decrease in BMD that returns to baseline after initiating GAHT.¼ It is important to abide by the International Society for Clinical Densitometry guidelines whenever ordering, performing, or reading a BMD scan for a gender-diverse patient.¼ There are no specific guidelines concerning vitamin D and calcium supplementation or the use of bisphosphonates in the transgender population, so the current recommendation is to abide by the guidelines for cisgender individuals.

Various Definitions of Failure Are Used in Studies of Patients Who Underwent Anterior Cruciate Ligament Reconstruction.

Purpose: To conduct a literature review to assess the definitions of anterior cruciate ligament reconstruction (ACLR) failure used throughout the orthopaedic literature. Methods: A systematic search of Embase, Ovid Medline, SPORTDiscus, and Web of Science was conducted by a university librarian to identity level I-IV clinical studies on ACLR failure. Inclusion criteria consisted of patients who underwent ACLR and included a definition of failure of ACLR. Patients who underwent anterior cruciate ligament (ACL) repairs, animal/cadaver studies, review studies, non-English language articles, and non-full text articles were excluded. Failure data were extracted from each study and categorized. Other data that were extracted included follow-up time after ACLR, failure reoperation rate, and failure reoperation procedure. Descriptive statistics was used to analyze the data. Results: Out of 2,775 studies, 104 (3.75%) met inclusion criteria and were analyzed in this review. The most common definition of ACLR failure included the use of a physical examination, specifically Lachman's test (21/104 [20.2%]), anterior laxity assessment, or a Pivot-Shift test (24/104 [35.2%]) or undergoing or requiring revision ACLR (39/104 [37.5%]). Although some studies used quantitative tests or imaging to help define "failure," others simply defined it as graft rerupture that was otherwise not defined (22/104 [22.5%]). Other common definitions included: the use of imaging (magnetic resonance imaging/radiographs) to confirm graft re-rupture (37/104 [35.6%]), patient-reported outcomes (recurrent instability)/patient reported outcomes measures (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Tegner) (18/104 [17.3%]), and the use of an arthrometer (KT-1000/2000, Rollimeter, or Kneelax) (17/104 [16.3%]). The least common definitions included graft failure or rerupture confirmed by arthroscopy (13/104 [12.5%]) and nonrevision surgery (2/104 [1.0%]). The failure rate of this procedure ranged from 0% to 100% depending on the definition of "failure." Conclusion: In this study, we found that a variety of definitions of failure are used among studies published in the orthopaedic literature. The most common criteria for failure of ACLR were the results of physical examination tests (35%), the need for undergoing a revision ACLR (36%), and the use of imaging to diagnose the failure (34%). About 17% of studies included in this review used patient-reported outcomes, specifically recurrent instability, or PROMs (IKDC, KOOS, Tegner) in their assessment of failure of ACLR. The least used definitions of "failure" of ACLR included nonrevision ACLR surgery (2%). Although some studies used similar tests or categories in their definition of failure, there were a variety of score and grade cutoff points between them. Level of Evidence: Level IV, systematic review of Level II-IV studies.

Perioperative allogenic blood transfusions are associated with increased fracture related infection rates, but not nonunion in operatively treated distal femur fractures.

INTRODUCTION: Distal femur fractures are common injuries that remain difficult for orthopedic surgeons to treat. High complication rates, including nonunion rates as high as 24% and infection rates of 8%, can lead to increased morbidity for these patients. Allogenic blood transfusions have previously been identified as risk factors for infection in total joint arthroplasty and spinal fusion surgeries. No studies have explored the relationship between blood transfusions and fracture related infection (FRI) or nonunion in distal femur fractures. METHODS: 418 patients with operatively treated distal femur fractures at two level I trauma centers were retrospectively reviewed. Patient demographics were collected including age, gender, BMI, medical comorbidities, and smoking. Injury and treatment information was also collected including open fracture, polytrauma status, implant, perioperative transfusions, FRI, and nonunion. Patients with less than three months of follow up were excluded. RESULTS: 366 patients were included in final analysis. One hundred thirty-nine (38%) patients received a perioperative blood transfusion. Forty-seven (13%) nonunions and 30 (8%) FRI were identified. Allogenic blood transfusion was not associated with nonunion (13% vs 12%, P = 0.87), but was associated with FRI (15% vs 4%, P<0.001). Binary logistic regression analysis identified a dose dependent relationship between number of perioperative blood transfusions and FRI: total transfusion ≥2 U PRBC RR= 3.47(1.29, 8.10, P = 0.02), ≥3 RR= 6.99 (3.01, 12.40, P<0.001), and ≥4 RR= 8.94 (4.03, 14.42, P<0.001). DISCUSSION: In patients undergoing operative treatment of distal femur fractures, perioperative blood transfusions are associated with increased risk of fracture related infection, but not the development of a nonunion. This risk association increases in a dose-dependent relationship with increasing total blood transfusions received.

Current Definitions of Failure in Lateral Ankle Instability Surgery: A Systematic Review.

BACKGROUND: "Failure" is a term that is frequently used to describe an unfavorable outcome for patients who undergo surgical treatment for lateral ankle instability (LAI). A standard definition of failure for the surgical treatment of ankle instability has not been established by clinicians and researchers. PURPOSE: To identify the definitions of ankle instability treatment failure that are currently in the literature and to work toward the standardization of the definition. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic search of MEDLINE, SPORTDiscus, CINAHL, Embase, and Web of Science was conducted to identify clinical studies that included patients who underwent surgical treatment for LAI and included information about surgical failure. Studies with level of evidence 1 to 4 were included in this review. Animal studies, biomechanical studies, cadaveric studies, review articles, and expert opinions were excluded. The included studies were then reviewed for definitions of failure of any surgical procedure that was performed to correct LAI. RESULTS: Of the 1200 studies found, 3.5% (42/1200) published between 1984 and 2021 met the inclusion criteria and were analyzed. After reviewing the data, we found numerous definitions were reported in the literature for LAI surgical failure. The most common was recurrent instability (40% [17/42]), followed by rerupture (19% [8/42]). For the original surgical procedure, the anatomic Broström-Gould technique was used most frequently (57% [24/42]). The failure rate of the Broström-Gould technique ranged from 1.1% to 45.2% depending on the definition of failure. CONCLUSION: There were multiple definitions of failure for the surgical treatment of LAI, which is one of the reasons why the rate of failure can vary greatly. The literature would benefit greatly from the standardization of the definition of ankle instability treatment failure. This definition should include specific, objective physical examination findings that eliminate the ambiguity surrounding failure.

Managing Post-Operative Pain in Orthopedic Patients: An International Comparison.

Introduction: Opioids play a crucial role in post-operative pain management in America, but not in some other countries. We sought to determine if a discrepancy in opioid use between the United States (U.S.) and Romania, a country that administers opioids in a conservative fashion, would show in subjective pain control differences. Methods: Between May 23, 2019, and November 23, 2019, 244 Romanian patients and 184 American patients underwent total hip arthroplasty or the surgical treatment of the following fractures: bimalleolar ankle, distal radius, femoral neck, intertrochanteric, and tibial-fibular. Opioid and non-opioid analgesic medication use and subjective pain scores during the first and second 24 hours after surgery were analyzed. Results: Subjective pain scores for the first 24 hours were higher among patients in Romania compared to the U.S. (p < 0.0001), but Romanians reported lower pain scores than U.S. patients in the second 24-hours (p < 0.0001). The quantity of opioids given to U.S. patients did not differ significantly based on sex (p = 0.4258) or age (p = 0.0975). However, females reported higher pain scores than male patients following the studied procedures (p = 0.0181). No sex-based differences in pain scores were noted among Romanian patients. Conclusions: Higher pain scores in American females, despite equivalent amounts of narcotics to their male counterparts, and the absence of a difference in Romanians suggested that the current American post-operative pain regimen may be tailored to the needs of male patients. In addition, it pointed to the impacts of gender, compared to sex, in pain experiences. Future research should look for the safest, most efficacious pain regimen suitable for all patients.

Debridement Versus Simple Scrubbing of External Fixator Pin Sites.

Introduction: Irrigation and debridement of external fixator pin sites are methods utilized by some orthopedic surgeons to minimize the risk of surgical site infections in patients undergoing definitive internal fixation after temporization in an external fixation device. This study aimed to determine if irrigation and debridement of external fixator pin sites leads to fewer deep surgical site infections, compared to simply scrubbing the external fixator pin sites with a chlorhexidine scrub-brush. Methods: This single center retrospective cohort study was performed at a university level I trauma center. All cases in which a single surgeon removed an external fixator and followed this with definitive open reduction and internal fixation (ORIF) in the same operative setting between October 2007 and October 2018 were reviewed. A total of 313 patients were temporized in 334 external fixators prior to ORIF and were included in the study. Results: Eighteen of the 179 Irrigation and Debridement cohort (10.0%) and 8 of the 155 Simple Scrubbing cohort (5.2%) had infections that required a return to the operating room. No statistical difference (p = 0.10) or meaningful effect size (Cohen's d = 0.18) were found between irrigation and debridement and simple scrubbing of external fixator pin sites. Conclusions: Given no significant differences were found in deep infection rates between debridement of pin sites versus simply scrubbing, it is reasonable to ask whether the time and resources required for debriding external fixator pin sites is worthwhile.

DXA Scan Variants in Transgender Patients.

Transgender and gender non-conforming (TGNC) individuals face numerous barriers to healthcare, which contribute to many health disparities. TGNC persons may choose gender-affirming therapies with surgery and/or hormone replacement therapy (HRT) to manage gender incongruence. Despite the expanding use of HRT, the long-term outcomes on bone health and metabolism, are still relatively unknown in the TGNC population. In 2019, the International Society of Clinical Densitometry (ISCD) released an official position statement on the appropriate use of dual energy x-ray absorptiometry (DXA) to measure bone density in the TGNC population. In this study, we reviewed which "sex" is currently utilized among providers when performing DXA scans to calculate T- and Z-scores for TGNC persons and how this compares to the positions published by the ISCD. A retrospective analysis was performed utilizing HERON queries and subsequent chart review. HERON is a type of Informatics for Integrating Biology and the Bedside software that was utilized to find sets of patients of interest from electronic medical record data while preserving patient privacy through a query interface tool. Project specific sets including patient demographics, medications, gonadectomy, and DXA scan information was created in HERON to make this highly detailed data of specific patients available to the investigators on the platform, as reviewed and retrieved by the Institutional Review Board. The qualitative DXA data obtained from chart review was determined as "correct" or "incorrect" based on positions provided from the ISCD. 10 DXA scans that met inclusion criteria were obtained between 9 TGNC patients. In total, 18 T-scores and Z-scores of the 10 DXAs were reviewed and scored. Based on ISCD positions, 67% of the T-score and Z-scores were calculated incorrectly; using the erroneous "sex" based standard to compare scores. Like DXA scans, many current healthcare standards and protocols are based on a patient's sex or gender, which may cause confusion amongst healthcare personnel who have not received proper training regarding the TGNC population. In this study, 67% of T-scores and Z-scores were calculated incorrectly based on ISCD recommendations. An additional prospective research design is required to determine the consequences of incorrectly calculated DXA scans for TGNC patients. Furthermore, future research is needed to determine HRT's effects on bone mineral density in the TGNC population in the United States.

Construction and Biological Evaluation of Small Libraries Based on the Intermediates within the Total Synthesis of Uvaretin.

Discovering therapeutic agents: New bioactive agents, either as sole or combinational agents, have been constructed through the synthetic manipulation of the intermediates within the total synthesis of the uvaretin class of natural products. It was found that increasing the hydrophobic character of the phenolic core correlates to a decrease in sole agent cytotoxicity. The synthesis of new, small chemical screening libraries (CSL) constructed from the intermediates of our total synthesis route of the uvaretin class of natural products is demonstrated herein. Numerous chalcone-based CSLs with various substitution on the phenolic groups within the chalcone core were assembled. Through cytotoxicity investigations, it was found that the level of hydrophobicity of the phenolic core of the chalcones gives biases: less cytotoxicity with more hydrophobic cores. In addition, it was observed that the potentiation, evaluated with 6-thiopurine in the pancreatic cancer cell line MIA PaCa-2, is tunable by the inclusion of less-hydrophobic character on the phenolic core. The role of the o-hydroxybenzyl group, present within the uvaretin family, was revealed to be cytotoxic in character. Merging all of the structure-activity relationship studies performed on the CSLs constructed in this effort led to the construction of a new chalcone hybrid possessing both a cytotoxic enone group and a small-molecule-potentiating, reduced enone group.

The winding road of the uvaretin class of natural products: from total synthesis to bioactive agent discovery.

Herein, we disclose the development of a synthetic route to gain access to the uvaretin class of chalcone natural products. In this, the construction of a small library was achieved, and the collection was evaluated for cytotoxicity and other biological properties. Uvaretin (1) was accessed via a seven-step route in an overall yield of 15.1%. Within this route, the unsaturated enone variant of uvaretin (2), also a natural product, was accessed in a 16.7% yield over six steps. This route provides a nearly three-fold increase in yields of 1 and 2 in comparison to the previous synthetic route accessing them in 5.8% and 3.0% overall yields, respectively. Evaluation of 1 and 2 revealed IC50 values between 2.0 and 5.1 µM in the cancerous cell lines HeLa, U937, A549, and MIA PaCa-2. Screening of the whole chalcone library set led to the discovery of over 30 compounds, within six cancerous cell lines, possessing single digit µM IC50 activity as sole agents. Furthermore, multiple library members were found to possess promising potentiating properties with known chemotherapeutic agents.

New methods to assess 6-thiopurine toxicity and expanding its therapeutic application to pancreatic cancer via small molecule potentiators.

6-Thiopurine (6TP) is a potent cytotoxic agent that is a clinically prescribed anti-metabolite employed in the treatment of numerous blood cancers since 1952. However, its reported severe toxicities limit its general usage in the clinic. We previously have undertaken investigations into identifying the mode of toxicity for 6TP, and have found that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU), is responsible for the in vitro inhibition of UDP-glucose dehydrogenase (UDPGDH) in a UV-vis method. In this method, inhibition was quantified through the quantification of NADH production, however, purines absorb at the same wavelength and thereby can interfere with the NADH detection. Herein, we report a HPLC method that allows for direct quantification of UDP-glucuronic acid, product from UDPGDH, for the assessment of inhibition towards UDPGDH with no interference from purines. In this method it was revealed that 6TP possesses a greater inhibitory properties than previously observed; 111 vs. 288 µM. Building upon the data collected from a previously performed rat hepatocyte study, which correlated our in vitro to in vivo inhibition theories about UDPGDH, we have developed a bio-mimic in vitro assay to aid in the inhibitory assessment of 6TP and analogs. In our efforts to expand the use of 6TP, and analogs constructed, our laboratory has undertaken a screening campaign to identify small molecule potentiators that work in synergy with 6TP in other types of cancers. Three chalcone-based compounds have been discovered through our total synthesis campaign of uvaretin, and it has been found that 11c has strong synergism with 6TP in the pancreatic cancer cell line MIA PaCa-2. Through the work presented herein, we reveal new methods to assess toxicity of 6TP and future analogs and new small molecules that work in synergy to expand the therapeutic applications of this neglected cytotoxic agent.