Risk factors for postoperative delirium in orthopaedic hip surgery patients: a database review.

BACKGROUND: Postoperative delirium is a common problem affecting admitted patients that decreases patient satisfaction and increases the cost and complexity of care. The purpose of this study was to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to compare rates and risk factors of postoperative delirium for total hip arthroplasty (THA) and hemiarthroplasty patients indicated for osteoarthritis or proximal femur fracture. METHODS: The 2021 NSQIP database was queried for patients using Current Procedural Terminology (CPT) codes for THA and hemiarthroplasty and ICD-10 codes for osteoarthritis or proximal femur fracture. Demographic, past medical history, preoperative labs, and functional status data were recorded. Procedural data were also collected. Finally, postoperative outcomes and complications were reviewed. RESULTS: Overall, 16% of patients had postoperative delirium. Delirium patients were older on average (82.4 years vs. 80.7 years, p < 0.001), had a lower BMI (19.5 vs. 24.8, p < 0.001), were more likely to have a history of dementia (54.6% vs. 13.6%, p < 0.001), were less likely to have an independent functional status (p < 0.001) or live alone (p < 0.001), and were more likely to have sustained a recent fall (p < 0.001). Delirium patients were more likely to be hyponatremic or hypernatremic (p = 0.002), anemic (p < 0.001), and severely dehydrated (p < 0.001), among other lab abnormalities. Delirium patients were also more likely to experience additional postoperative complications, including pneumonia, pulmonary embolism, urinary tract infection, stroke, cardiac arrest, sepsis, and unplanned reoperation and readmission after discharge (all p < 0.05). CONCLUSIONS: In this study, factors associated with postoperative delirium in patients undergoing hemiarthroplasty and THA were identified, including older age, lower BMI, certain medical conditions, decreased functional status, certain lab abnormalities, and postoperative complications. These findings can be used by clinicians to better inform care and to determine when orthopaedic joint replacement patients may be at an increased risk for postoperative delirium.

Preoperative demographics and laboratory markers may be associated with early dislocation after total hip arthroplasty.

PURPOSE: The purpose of this study was to identify modifiable medical comorbidities, laboratory markers and flaws in perioperative management that increase the risk of acute dislocation in total hip arthroplasty (THA) patients. METHODS: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Demographic data, preoperative laboratory values, recorded past medical history, operative details as well as outcome and complication information were collected. The study population was divided into two cohorts: non-dislocation and dislocation patients. Statistics were performed to compare the characteristics of both cohorts and to identify risk factors for prosthetic dislocation (α < 0.05). RESULTS: 275,107 patients underwent primary THA in 2007 to 2020, of which 1,258 (0.5%) patients experienced a prosthetic hip dislocation. Demographics between non-dislocation and dislocation cohorts varied significantly in that dislocation patients were more likely to be female, older, with lower body mass index and a more extensive past medical history (all p < 0.05). Moreover, hypoalbuminemia and moderate/severe anemia were associated with increased risk of dislocation in a multivariate model (all p < 0.05). Finally, use of general anesthesia, longer operative time, and longer length of hospital stay correlated with greater risk of prosthetic dislocation (all p < 0.05). CONCLUSIONS: Elderly female patients and patients with certain abnormal preoperative laboratory values are at risk for sustaining acute dislocations after index THA. Careful interdisciplinary planning and medical optimization should be considered in high-risk patients as dislocations significantly increase the risk of sepsis, cerebral vascular accident, and blood transfusions on readmission.

Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study.

BACKGROUND: Studies have reported promising results of mesenchymal stem cell therapies for skin aging. However, in the use of mesenchymal stem cells, some drawbacks including rarely possible tumorigenicity and low engraftment rates have limited their widespread clinical use. Adipose tissue stem cell-derived exosomes (ASCEs) are emerging as effective cell-free therapeutic agents. AIMS: It was evaluated the clinical efficacy of combining the application of human ASCE-containing solution (HACS) with microneedling to treat facial skin aging. METHODS: A 12-week, prospective, randomized, split-face, comparative study was conducted. Twenty-eight individuals underwent three treatment sessions separated by 3-week intervals and were followed up for 6 weeks after the last session. At each treatment session, HACS and microneedling were administered to one side of the face, and normal saline solution and microneedling were administered to the other side as a control. RESULTS: The Global Aesthetic Improvement Scale score was significantly higher on the HACS-treated side than on the control side at the final follow-up visit (p = 0.005). Objective measurements obtained by different devices including PRIMOS Premium, Cutometer MPA 580, Corneometer CM 825, and Mark-Vu confirmed greater clinical improvements in skin wrinkles, elasticity, hydration, and pigmentation on the HACS-treated side than on the control side. The results of the histopathological evaluation were consistent with the clinical findings. No serious adverse events were observed. CONCLUSIONS: These findings demonstrate that combined treatment using HACS and microneedling is effective and safe for treating facial skin aging.

Repeat High-Dose Dexamethasone May Improve Recovery 48 Hours after Total Hip Arthroplasty.

Objectives: Perioperative dexamethasone is an effective anti-emetic and systemic analgesic in total hip arthroplasty (THA) that may reduce opioid consumption and enhance rapid recovery. However, there is no consensus on the optimal perioperative dosing that is safe and effective for faster rehabilitation and improved pain control while maintaining safe blood glucose levels. Methods: A retrospective review of 101 primary THA patients at a single institution who received perioperative dexamethasone was conducted. Patients were stratified by dexamethasone induction dosage (10 mg as high, <6mg as low) and whether a repeat dose was given 16-24 hours postoperatively. Age, gender, BMI, diabetes status, and ASA were controlled between groups. The pain was evaluated with inpatient morphine milligram equivalents (MME) requirements and visual analog scale (VAS) at 8, 16, and 24 hours postoperatively. Mobility was assessed by inpatient ambulation distance, Boston AM-PAC mobility score, and percentage of gait assistance as determined by a physical therapist. Secondary outcomes included postoperative nausea and vomiting (PONV) limiting therapy sessions, PONV requiring breakthrough anti-emetics, glucose levels, surgical site infection, wound healing complications, and discharge destination. Results: Compared to patients receiving one dose of high or low dexamethasone, patients receiving two dosages of high-dose dexamethasone had significantly further ambulation distance and lower percentage of gait assistance on postoperative day 2. A generalized linear model also predicted that any repeat dexamethasone, regardless of dosage, significantly improved ambulation distance and gait assistance compared to the one-dose cohort. There was no statistically significant difference between VAS scores, MME requirements, PONV, postoperative glucose levels >200, discharge destination, or risk of infection between groups. Conclusion: A repeat high-dose dexamethasone, the morning after surgery, may improve percentage of gait assistance and ambulation endurance on postoperative day two. There was no risk of uncontrolled glucose levels or infections compared to receiving one dose of dexamethasone at induction.

Branched-chain amino acid catabolism in muscle affects systemic BCAA levels but not insulin resistance.

Elevated levels of plasma branched-chain amino acids (BCAAs) have been associated with insulin resistance and type 2 diabetes since the 1960s. Pharmacological activation of branched-chain α-ketoacid dehydrogenase (BCKDH), the rate-limiting enzyme of BCAA oxidation, lowers plasma BCAAs and improves insulin sensitivity. Here we show that modulation of BCKDH in skeletal muscle, but not liver, affects fasting plasma BCAAs in male mice. However, despite lowering BCAAs, increased BCAA oxidation in skeletal muscle does not improve insulin sensitivity. Our data indicate that skeletal muscle controls plasma BCAAs, that lowering fasting plasma BCAAs is insufficient to improve insulin sensitivity and that neither skeletal muscle nor liver account for the improved insulin sensitivity seen with pharmacological activation of BCKDH. These findings suggest potential concerted contributions of multiple tissues in the modulation of BCAA metabolism to alter insulin sensitivity.

Alkaline Phosphatase is an Independent Risk Factor for Periprosthetic Fractures in Total Joint Arthroplasty.

BACKGROUND: Serum alkaline phosphatase (ALP) is a biomarker for chronic low-grade inflammation along with hepatobiliary and bone disorders. High abnormal ALP levels in blood have been associated with metabolic bone disease and high bone turnover. METHODS: All primary total hip and knee arthroplasties from 2005 to 2019 were queried from the National Surgical Quality Improvement Program database. Patients with available serum ALP levels were included and stratified to low (<44 IU/L), normal (44 to 147 IU/L), and high (>147 IU/L). A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor of complications. RESULTS: The analysis included 324,592 patients, consisting of 11,427 low ALP, 305,977 normal ALP, and 7,188 high preoperative ALP level patients undergoing total joint arthroplasty. Adjusted multivariate logistic regression analysis showed high ALP level patients had an overall increased risk of readmission within 30 days of surgery compared with the control group (odds ratio [OR], 1.69; P < 0.01). High ALP patients also had an increased risk of postoperative periprosthetic fracture (OR, 1.6), postoperative wound infection (OR, 1.81), pneumonia (OR, 2.24), renal insufficiency (OR, 2.39), cerebrovascular disease (OR, 2.2), postoperative bleeding requiring transfusion (OR, 1.83), sepsis (OR, 2.35), length of stay > 2 days (OR, 1.47), Clostridium difficile infection (OR, 2.07), and discharge to a rehab facility (OR, 1.41) (all P < 0.05). A low ALP level was also associated with increased postoperative bleeding transfusion risk (OR, 1.12; P < 0.01) and developing a deep vein thrombosis (OR, 1.25; P = 0.03). CONCLUSION: Abnormal serum ALP levels in patients undergoing primary total joint arthroplasty are associated with increased postoperative periprosthetic fracture risk and medical complications requiring increased length of stay and discharge to a rehabilitation facility.

Targeting Immune-Fibroblast Crosstalk in Myocardial Infarction and Cardiac Fibrosis.

Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remains unexplored and there are currently no therapeutics to target fibrosis. Here, we performed multi-omic single-cell gene expression, epitope mapping, and chromatin accessibility profiling in 38 donors, acutely infarcted, and chronically failing human hearts. We identified a disease-associated fibroblast trajectory marked by cell surface expression of fibroblast activator protein (FAP), which diverged into distinct myofibroblasts and pro-fibrotic fibroblast populations, the latter resembling matrifibrocytes. Pro-fibrotic fibroblasts were transcriptionally similar to cancer associated fibroblasts and expressed high levels of collagens and periostin (POSTN), thymocyte differentiation antigen 1 (THY-1), and endothelin receptor A (EDNRA) predicted to be driven by a RUNX1 gene regulatory network. We assessed the applicability of experimental systems to model tissue fibrosis and demonstrated that 3 different in vivo mouse models of cardiac injury were superior compared to cultured human heart and dermal fibroblasts in recapitulating the human disease phenotype. Ligand-receptor analysis and spatial transcriptomics predicted that interactions between C-C chemokine receptor type 2 (CCR2) macrophages and fibroblasts mediated by interleukin 1 beta (IL-1ß) signaling drove the emergence of pro-fibrotic fibroblasts within spatially defined niches. This concept was validated through in silico transcription factor perturbation and in vivo inhibition of IL-1ß signaling in fibroblasts where we observed reduced pro-fibrotic fibroblasts, preferential differentiation of fibroblasts towards myofibroblasts, and reduced cardiac fibrosis. Herein, we show a subset of macrophages signal to fibroblasts via IL-1ß and rewire their gene regulatory network and differentiation trajectory towards a pro-fibrotic fibroblast phenotype. These findings highlight the broader therapeutic potential of targeting inflammation to treat tissue fibrosis and restore organ function.

Preoperative Malnutrition and Metabolic Markers May Predict Periprosthetic Fractures in Total Hip Arthroplasty.

Background: Periprosthetic fractures are a devastating complication of total hip arthroplasty (THA) and are associated with significantly higher mortality rates in the postoperative period. Given the strain that periprosthetic fractures place on the patient as well as the healthcare system, identifying and optimizing medical comorbidities is essential in reducing complications and improving outcomes. Methods: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program database. Demographic data, preoperative laboratory values, medical comorbidities, hospital course, and acute complications were collected and compared between patients with and without readmission for a periprosthetic fracture. A multivariate logistic regression analysis was performed to determine associated independent risk factors for periprosthetic fractures after index THA. Results: The analysis included 275,107 patients, of which 2539 patients were readmitted for periprosthetic fractures. Patients with postoperative fractures were more likely to be older (>65 years), females, BMI >40, and increased medical comorbidities. Preoperative hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rates were independent risk factors for sustaining a periprosthetic fracture and readmission within 30 days. Modifiable patient-related factors of concurrent smoking and chronic steroid use at the time of index THA were also independent risk factors for periprosthetic fractures. Inpatient metrics of longer length of stay, operative time, and discharge to rehab predicted postarthroplasty fracture risk. Readmitted fracture patients subsequently had increased risks of developing a surgical site infection, urinary tract infection, and requiring blood transfusions. Conclusions: Patients with hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rate are at increased risk for sustaining periprosthetic fractures after THA. Preoperative optimization with close monitoring of metabolic markers and modifiable risk factors may help not only prevent acute periprosthetic fractures but also associated infection and bleeding risk with fracture readmission.

The impact of dehydration on short-term postoperative complications in total knee arthroplasty.

BACKGROUND: As healthcare economics shifts towards outcomes-based bundled payment models, providers must understand the evolving dynamics of medical optimization and fluid resuscitation prior to elective surgery. Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total knee arthroplasty (TKA) to reduce postoperative complications and inpatient costs. METHODS: All primary TKA from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database, and patients were compared based on dehydration status: Blood Urea Nitrogen Creatinine ratio (BUN/Cr) < 20 (non-dehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately-dehydrated), 25 < BUN/Cr (severely-dehydrated). A sub-group analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed. RESULTS: The analysis included 344,744 patients who underwent TKA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of non-home discharge, postoperative transfusion, postoperative deep vein thrombosis (DVT), and increased length of stay (LOS) (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of non-home discharge, progressive renal insufficiency, urinary tract infection (UTI), postoperative transfusion, and extended LOS (all p < 0.01). CONCLUSION: BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Design; Prognosis Study.

Kinematic Alignment May Reduce Opioid Consumption and Length of Stay Compared to Mechanically Aligned Total Knee Arthroplasty.

OBJECTIVE: Previous studies have sought to determine the effects of total knee arthroplasty (TKA) using kinematic alignment (KA) versus mechanical alignment (MA) to reproduce the native knee alignment and soft tissue envelope for improved patient satisfaction. There are limited studies that compare acute perioperative outcomes between KA and MA patients as it pertains to pain-related opioid consumption and hospital length of stay (LOS). This study aims to compare early KA and MA in restoring function and rehabilitation after surgery to reduce hospitalization and opioid consumption. METHODS: A retrospective review of 42 KA and 58 MA primary TKA patients performed by a single surgeon between 2020-2021 was conducted. Demographics were controlled between groups and radiographic measurements and functional outcomes were compared. Pain was evaluated with inpatient/outpatient morphine milligram equivalents (MME) and visual analogue scale (VAS) scores. Mobility was assessed using multiple measures by a physical therapist. Mean preoperative and 3-month postoperative flexion range of motion (ROM) were analyzed, and overall complications, LOS, and non-home discharge between groups compared. Continuous variables were compared using the Wilcoxon rank-sum test, and categorical variables were compared using the chi-square or Fisher exact test. Statistical significance was set at P < 0.05. RESULTS: KA patients had shorter LOS (1.8 vs 3.1 days) and less cumulative opioid requirements compared to MA patients (578 vs 1253 MME). On postoperative day 0, KA patients ambulated on average twice the distance of MA patients (20 vs 6.5 feet). KA patients had residual tibia component in varus (1.4° vs -0.3°), femoral component in valgus (-1.9° vs 0.2°), and valgus joint line obliquity compared with MA (-1.5° vs 0.2°). There were no significant differences between 3-month postoperative flexion arc motion, discharge destination, KOOS or SF-12 outcomes, and surgical complication rates between groups. CONCLUSIONS: By restoring the native joint line obliquity and minimizing the frequency of ligament releases, KA for TKA may improve pain relief, early mobility, and decreased length of stay compared with traditional methods of establishing neutral limb axis by MA.

Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.

Cryoneurolysis Is a Safe, Effective Modality to Improve Rehabilitation after Total Knee Arthroplasty.

Although long term pain and mobility outcomes in total knee arthroplasties (TKA) are successful, many patients experience significant amount of debilitating pain during the immediate post-operative period that necessitates narcotic use. Percutaneous cryoneurolysis to the infrapatellar saphenous and anterior femoral cutaneous nerves may help to better restore function and rehabilitation after surgery while limiting narcotic consumption. A retrospective chart review of primary TKA patients receiving pre-operative cryoneurolysis from 2019 to 2020 was performed to assess total opioid morphine milligram equivalents (MME) consumed inpatient and at interval follow-up. Demographics and medical comorbidities were compared between cryoneurolysis and age-matched control patients to assess baseline characteristics. Functional rehabilitation outcomes, including knee range of motion (ROM), ambulation distance, and Boston AM-PAC scores, as well as patient reported outcomes using the KOOS JR and SF-12 scores were analyzed using STATA 17 Software. The analysis included 29 cryoneurolysis and 28 age-matched control TKA patients. Baseline demographics and operative technique were not significant between groups. Although not statistically significant, cryoneurolysis patients had a shorter length of stay (2.5 vs. 3.5 days) and overall less inpatient and outpatient MME requirements. Cryoneurolysis patients had statistically significant improved 6-week ROM and 1-year follow-up KOOS JR and SF-12 mental scores compared to the control. There were no differences in complication rates. Cryoneurolysis is a safe, effective treatment modality to improve active functional recovery and patient satisfaction after TKA by reducing MME requirements. Patients who underwent cryoneurolysis had on average fewer MME prescribed during the perioperative period, improved active ROM, and improved patient-reported outcomes with no associated increased risk of infections, deep vein thrombosis, or neurologic complications.

Prior Diagnosis of COVID Has No Increased Complications in Total Joint Arthroplasty.

Introduction Although a substantial portion of the United States population has been infected with and recovered from Coronavirus Disease-19 (COVID-19), many patients may have persistent symptoms and complications from disease-driven respiratory disease, arrhythmias, and venous thromboembolism (VTE). With institutions resuming elective total joint arthroplasties (TJA), it is unclear whether a prior resolved diagnosis of COVID has any implications on postoperative outcomes. Methods All elective TJA performed in 2021 at our institution were retrospectively reviewed and a history of prior COVID+ result recorded. Baseline demographics, days from prior COVID+ result to surgery date, preoperative methicillin-resistant Staphylococcus aureus (MRSA) nares colonization, and laboratory markers were obtained to determine baseline characteristics. Postoperative estimated blood loss (EBL), length of stay (LOS), rate of revision surgery, and discharge destination were compared between groups. Perioperative and postoperative rates of VTE, urinary tract infection (UTI), pneumonia, postoperative oxygen supplementation, cardiac arrhythmia, renal disease, sepsis, and periprosthetic joint infections within six months of surgery were recorded. Results Of the 155 elective TJA performed in 2021, 24 patients had a prior COVID+ diagnosis with a mean of 253 days from positive result to surgery date. There were no significant differences in baseline demographics, comorbidities, and preoperative lab markers between groups. Surgeries on patients with a prior COVID+ had a significantly higher EBL (260 vs 175cc), but postoperative outcomes of VTE, UTI, pneumonia, oxygen supplementation requirement, nares MRSA+, cardiac disease, and infection rates between groups were similar. Bivariate logistic regression revealed increased days from COVID+ diagnosis (>6 months) to surgery date were associated with a shorter LOS. Conclusion Although a prior COVID+ diagnosis had increased intraoperative blood loss, there were no significant differences in respiratory, infectious, cardiac, and thromboembolic complications up to six months after elective TJA. This study suggests that asymptomatic C+ patients receiving elective TJA do not require more aggressive prophylactic anticoagulation or antibiotic regimens to prevent VTE or perioperative infections. As institutions around the nation resume pre-COVID rates of arthroplasty surgeries, a prior diagnosis of COVID appears to have no effects on postoperative complications.

Chlorhexidine gluconate lavage during total joint arthroplasty may improve wound healing compared to dilute betadine.

PURPOSE: Intraoperative wound irrigation prior to closure during total joint arthroplasty (TJA) is an essential component of preventing infections and limiting health care system costs. While studies have shown the efficacy of dilute betadine in reducing infection risk, there remains concerns over its safety profile and theoretical inactivation by blood and serum. This study aims to compare infection and wound complications between chlorhexidine gluconate (CHG) and betadine lavage during TJA. METHODS: All primary TJA between 2019-2021 were analyzed at a single institution, and periprosthetic joint infection (PJI), wound drainage, 30 and 90-day emergency room (ER) readmission due to wound complications, aseptic loosening, and revision surgery rate were compared between patients undergoing intraoperative CHG versus betadine lavage prior to closure. Baseline demographics were controlled, and multivariate logistic regression was performed to compare complication rates. RESULTS: A total of 410 TJA, including 160 hip and 250 knee arthroplasties were included. Compared to the dilute betadine cohort, all TJA patients undergoing CHG lavage had a statistically significant lower 30 and 90-day emergency room readmission rate due to wound complications. Both hip and knee arthroplasty patients with CHG had a statistically significant lower rate of postoperative superficial drainage and dressing saturation at clinic follow-up, but only knee arthroplasty patients had significant decreased readmission rate for incisional wound vacuum placement and close inpatient monitoring of wound healing. Among all TJA, there was no significant association in the rate of PJI requiring return to the OR between groups. CONCLUSIONS: Although betadine is cost-effective and has been shown to reduce PJI rates, there remains concerns in the literature over soft tissue toxicity and wound healing. This study suggests CHG may be as efficacious as dilute betadine in preventing PJI while also decreasing the risk of superficial drainage and wound complications needing unplanned ER visits during the acute postoperative period.

Orthopedic Treatment of Pycnodysostosis: A Systematic Review.

Pycnodysostosis (PYCD) is an autosomal recessive lysosomal storage disorder of the bone which leads to stereotypical abnormalities consisting of, but not limited to, sclerotic and fragile bone, shortened distal phalanges, and obtuse mandibular angle. Current literature describes the otolaryngological manifestations and treatment of this disorder; however, the treatment of orthopedic fractures in PYCD patients is seldom described and remains a controversial topic. We aim to systematically review the current evidence regarding the optimal treatment of PYCD patients with fractures. We performed a literature search using PubMed, MEDLINE, Web of Science, and Google Scholar databases. Elig-ibility criteria consisted of English-language literature of PYCD patients undergoing treatment for orthopedic surgery fractures. Non-English papers or literature focused on maxillofacial manifestations/treatment were excluded. The database search resulted in the identification of 500 articles. After removing duplicates and enforcing our inclusion criteria, 29 case reports/series (40 patients) were included. The average age was 31.25 (-±18.2) years, with 57.5% of patients being female. Overall, 62.5% of patients had consanguineous parents. Additionally, 86.2% reported a history of previous fractures while 47.5% reported a spontaneous or minor trauma fracture, with most fractures occurring in the femur (60.0%) and tibia (40.0%). Radiographic features consisted of densification in the femur 45.0% (18/40), tibia 37.5% (15/40), and spine 25.0% (10/40). Overall, 84.2% of patients were treated with surgical management consisting of internal plate fixation (IPF) (48.3%), intramedullary fixation (20.7%), and Ilizarov external fixation (IEF) (13.8%). Overall, the refracture rate was 25.0% and was lowest in intramedullary fixation (0/6), compared to IPF (3/14) and IEF (3/4). Average time until refracture was 40.6 months (3-132 months). Long-term follow-up is recommended in patients with PYCD due to the propensity for fractures/refractures. While this study provides the groundwork for the treatment of PYCD patients, further research with higher-evidence studies should be conducted to establish the optimal orthopedic treatment of this disorder.

An Ultrasound-Guided Hemispherical Phased Array for Microbubble-Mediated Ultrasound Therapy.

GOAL: To develop a low-cost magnetic resonance imaging (MRI)-free transcranial focused ultrasound (FUS) system for microbubble-mediated therapy. METHODS: A 128-element 11 MHz array for skull localization was integrated within a 256-module multi-frequency (306/612/1224 kHz) dual-mode phased array. The system's transcranial transmit and receive performance was evaluated with ex-vivo human skullcaps using phase aberration corrections calculated from computed tomography (CT)-based simulations via ultrasound-based (USCT) and landmark-based (LMCT) registrations, and a gold-standard fixed source emitter (FSE)-based method. RESULTS: Displacement and rotation registration errors of 1.4 ± 0.4 mm and 2.1 ± 0.2 ° were obtained using USCT, resulting in sub-millimeter transmit targeting errors driven at 306 kHz (0.9 ± 0.2 mm) and 612 kHz (0.9 ± 0.3 mm), and source localization errors of 1.0 ± 0.3 mm and 0.6 ± 0.2 mm at receive frequencies of 306 kHz and 612 kHz, respectively (mean ± SD). Similar errors were obtained using LMCT and no significant differences between these two approaches were found on either transmit (p = 0.64/0.99) or receive (p = 0.45/0.36) at 306 kHz/612kHz. During volumetric multi-point exposures, approximately 70% and 60% of the transmit frames in which microbubble activity was detected via FSE were recovered using USCT when imaging at the second-harmonic and half-harmonic, respectively, compared to 60% and 69% using LMCT. CONCLUSION: This low-cost ultrasound-guided transcranial FUS system affords USCT skull registration with accuracy comparable to LMCT methods. SIGNIFICANCE: Such systems have great potential to advance the adoption of microbubble-mediated FUS brain therapy by improving access to the technology.

Tightening and Reduction of Unwanted Submental Fat Using Triple-Layer High-Intensity Focused Ultrasound: Clinical and 3-Dimensional Imaging Analysis.

BACKGROUND: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence of their use. OBJECTIVE: The authors sought to evaluate the safety and efficacy of a novel triple-layer high-intensity focused ultrasound (HIFU) regimen for SMF reduction. METHODS: Forty Korean subjects with moderate/severe SMF were evaluated after receiving a session of triple-layer HIFU treatments (using 3.0-, 4.5-, and 6.0-mm focusing transducers). The objective evaluation based on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and patients' satisfaction based on the 7-point Subject Self-Rating Scale (SSRS) were determined 8 weeks after treatment. Three-dimensional image analysis was also performed. RESULTS: At the follow-up visit, the proportion of treatment responders defined as subjects with ≥1-point improvement in CR-SMFRS was 62.5%, and the proportion of patients satisfied with appearance of their face and chin (score ≥4 on the SSRS) was 67.5% of the total patients. The results of 3-dimensional analysis were consistent with clinical observations. Only mild and transient side effects were observed for some patients with no serious adverse effects. CONCLUSION: The triple-layer HIFU regimen including the novel 6.0-mm transducer has benefits for tightening and rejuvenation of the area with unwanted SMF, showing reasonable safety profiles.

Implementation of a Skull-Conformal Phased Array for Transcranial Focused Ultrasound Therapy.

OBJECTIVE: To implement a skull-conformal phased array for ultrasound-guided transcranial focused ultrasound therapy with improved patient comfort. METHODS: Using patient-specific computed tomography and MRI neuroimaging data, tightly-conforming helmet scaffolds were designed computationally. The helmet scaffolds were designed to hold reusable transducer modules at near-normal incidence in an optimal configuration for the treatment location(s) of interest. Numerical simulations of trans-skull ultrasound propagation were performed to evaluate different conformal array designs and to compare with hemispherical arrays similar to those employed clinically. A 4096-element phased array was constructed by 3D printing a helmet scaffold optimised for an ex vivo human skullcap, and its performance was evaluated via benchtop and in vivo experiments. RESULTS: Acoustic field measurements confirmed the system's ability to focus through human skull bone using simulation-based transcranial aberration corrections. Preliminary in vivo testing demonstrated safe trans-human skull blood-brain barrier (BBB) opening in rodents. CONCLUSION: Patient-specific conformal ultrasound phased arrays appear to be a feasible and safe approach for conducting transcranial BBB opening procedures. SIGNIFICANCE: Skull-conformal phased arrays stand to improve patient comfort and have the potential to accelerate the adoption of transcranial FUS therapy by improving access to the technology.

Spatio-temporal focal spot characterization and modeling of the NIF ARC kilojoule picosecond laser.

The advanced radiographic capability (ARC) laser system, part of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, is a short-pulse laser capability integrated into the NIF. The ARC is designed to provide adjustable pulse lengths of ∼1-38ps in four independent beamlets, each with energies up to 1 kJ (depending on pulse duration). A detailed model of the ARC lasers has been developed that predicts the time- and space-resolved focal spots on target for each shot. Measurements made to characterize static and dynamic wavefront characteristics of the ARC are important inputs to the code. Modeling has been validated with measurements of the time-integrated focal spot at the target chamber center (TCC) at low power, and the space-integrated pulse duration at high power, using currently available diagnostics. These simulations indicate that each of the four ARC beamlets achieves a peak intensity on target of up to a few 1018W/cm2.

Periprosthetic Tissue Reaction Independent of LTT Result and Implanted Materials in Total Knee Arthroplasty.

BACKGROUND: An allergic reaction may rarely cause a painful or stiff total knee arthroplasty (TKA). However, no consensus diagnostic criteria for TKA immune failure exist. Lymphocyte transformation testing (LTT) measures immune sensitivity to various materials, but its role in diagnosing an allergic reaction to a TKA has not been established. This study compares TKA periprosthetic tissues in a) LTT-positive versus -negative patients and b) patients with conventional CoCrNi versus hypoallergenic implants. METHODS: Periprosthetic tissues from 26 revision cases of well-fixed, aseptic, but painful or stiff TKAs were analyzed. Twelve patients LTT positive for nickel (Ni) were matched as a cohort to 6 LTT-negative patients. In 4 patients LTT positive for Ni, tissue from first revision of CoCrNi implants was compared with tissue from subsequent revision of hypoallergenic implants. Histology was evaluated using the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) score. RESULTS: No correlation was found between LTT and any ALVAL score component. The mean total ALVAL score was 3.8 ± 1.5 for LTT-negative patients and 3.3 ± 1.2 for LTT-positive patients (P = .44). The mean total ALVAL score at revision of CoCrNi implants was 3.0 ± 1.8 compared with 5.8 ± 0.5 at rerevision of hypoallergenic implants (P = .053). CONCLUSION: Periprosthetic TKA tissue reactions were indistinguishable between LTT-positive and -negative patients. LTT does not predict the periprosthetic tissue response. ALVAL scores of hypoallergenic revision implant tissue trended higher than primary CoCrNi implant tissue. A positive LTT may not indicate that a periprosthetic immune reaction is the cause of pain and stiffness after TKA. LEVEL OF EVIDENCE: 3, retrospective cohort study.