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This retrospective analysis evaluated the impact of exercise, sex, and diet on ACE2 and TMPRSS2 mRNA levels in preclinical swine heart failure models. Unlike normal exercise intensities, exercise training of an intensity tolerable to a patient with heart failure had no influence on ACE2 or TMPRSS2 mRNA. In a tissue-specific manner, ACE2 mRNA levels were altered due to sex and Western diet, whereas TMPRSS2 mRNA levels were sensitive to sex, Western diet, and pig species.

Background: Meniscal allograft transplantation (MAT) has been developed as a treatment for meniscal deficiency. Despite promising outcomes, there are no real-time methods to evaluate graft survivorship and predict functional outcomes. Hypothesis: Assessment of serum and urine biomarkers could be used to develop biomarker panels—prognostic (1- and 3-month postsurgical time points) and diagnostic (6-month time point)—based on strong associations with clinically relevant outcome metrics obtained 6 months after surgery. Study Design: Descriptive laboratory study. Methods: Twelve adult purpose-bred research hounds were included and underwent medial meniscal release to induce meniscal deficiency. Three months after meniscal release surgery, medial menisci were replaced with fresh-frozen meniscus (n = 4), fresh meniscus (n = 4), or fresh meniscotibial osteochondral allograft (n = 4) such that a spectrum of pain and functional outcomes could be anticipated. Serum and urine from all dogs were collected preoperatively and at 1, 3, and 6 months after MAT surgery. Dogs were assessed for pain-related and functional outcomes at the same time points. To develop a prognostic panel of biomarkers, biomarker data from the 1- and 3-month post-MAT surgery time points were used to model 6-month clinical outcomes. A diagnostic panel of biomarkers was developed using data from the 6-month post-MAT surgery to model 6-month clinical outcomes. Primary outcomes for pain and function were visual analog scale (VAS) and operated limb percentage total pressure index (%TPI), respectively. Using random subject effects, linear mixed models were used to develop prognostic biomarker panels, and linear fixed-effect models were used to develop diagnostic biomarker panels, with variance explained for each panel reported ( R2) along with individual biomarker relationships. Results: Across prognostic biomarker panels, a panel including serum IL-6, IL-8, IL-10, and IL-18 was fit for the primary functional outcome, operated limb %TPI ( R2 = 0.450), whereas a panel including serum CTX-II and OPG was fit for the primary pain-related outcome, VAS ( R2 = 0.516). Across diagnostic biomarker panels, a panel including serum MMP-1 and MMP-3 and urine PINP and TIMP-1 was fit for %TPI ( R2 = 0.863). Separately, a panel including urine CTX-I, CTX-II, IL-8, MMP-2, and TIMP-1 was fit as diagnostic biomarkers for the VAS for pain ( R2 = 0.438). Conclusion: Biomarker panels of selected serum and/or urine proteins can model clinically relevant metrics for function and pain in a preclinical model of MAT. Clinical Relevance: Biomarker panels could be used to provide real-time diagnostic and prognostic data regarding outcomes after MAT.

Limited reports exist regarding adeno-associated virus (AAV) biodistribution in swine. This study assessed biodistribution following antegrade intracoronary and intravenous delivery of two self-complementary serotype 9 AAV (AAV9sc) biologics designed to target signaling in the cardiomyocyte considered important for the development of heart failure. Under the control of a cardiomyocyte-specific promoter, AAV9sc.shmAKAP and AAV9sc.RBD express a small hairpin RNA for the perinuclear scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) and an anchoring disruptor peptide for p90 ribosomal S6 kinase type 3 (RSK3), respectively. Quantitative PCR was used to assess viral genome (vg) delivery and transcript expression in Ossabaw and Yorkshire swine tissues. Myocardial viral delivery was 2–5 × 105 vg/µg genomic DNA (gDNA) for both infusion techniques at a dose ∼1013 vg/kg body wt, demonstrating delivery of ∼1–3 viral particles per cardiac diploid genome. Myocardial RNA levels for each expressed transgene were generally proportional to dose and genomic delivery, and comparable with levels for moderately expressed endogenous genes. Despite significant AAV9sc delivery to other tissues, including the liver, neither biologic induced toxic effects as assessed using functional, structural, and circulating cardiac and systemic markers. These results indicate successful targeted delivery of cardiomyocyte-selective viral vectors in swine without negative side effects, an important step in establishing efficacy in a preclinical experimental setting.

Background: Surgical site infections (SSIs) significantly influence outcomes and health care costs after orthopaedic surgery, but they have not been well characterized for osteochondral allograft (OCA) transplantation with or without meniscal allograft transplantation (MAT). Purpose: To characterize the incidence, cost, and risk factors associated with potential or confirmed SSIs after large single-surface, multisurface, or bipolar allograft transplantation in the knee. Study Design: Case-control study; Level of evidence, 3. Methods: Prospectively collected registry data were analyzed for patients who underwent primary or revision OCA transplantation with or without MAT in the knee. The Centers for Disease Control and Prevention (CDC) guidelines were used to define SSIs and calculate the SSI incidence. Both potential and confirmed SSIs were analyzed to determine related treatment methods, calculate associated health care costs, and characterize risk factors based on the OCA surgery type (single-surface, multisurface, bipolar, ±MAT), American Society of Anesthesiologists physical status classification system, surgery duration, length of stay, age, sex, body mass index (BMI), and current tobacco use. Results: A total of 224 patients were included in the analysis. There were 2 SSIs in 1 patient that met CDC criteria, such that the incidence for this patient population was 0.9%. An additional 7 patients (3.1%) were examined for potential infections not classified as SSIs. Patients with potential or confirmed SSIs had a significantly higher mean BMI compared to patients with no evidence of an SSI ( P 35 (odds ratio, 9.1) and tobacco use (odds ratio, 6.6) were associated with greater odds for a potential or confirmed SSI. The mean health care costs were $6101 for patients who required additional emergency room visits and/or irrigation and debridement within 90 days postoperatively for potential or confirmed SSIs, $19 for patients with potential superficial incisional SSIs, and $12,100 for patients who experienced a potential or confirmed deep incisional or organ/space SSI >90 days from surgery. Conclusion: Large OCA transplantation with and without MAT were associated with a low incidence of confirmed SSIs (0.9%), and patients with BMI >35 and current tobacco use had greater odds of an SSI. Potential and confirmed SSIs were associated with unscheduled appointments, additional surgical procedures, and higher costs.

Peripherally inserted central catheter (PICC) placement is necessary for delivery of intravenous (IV) antibiotics to treat bone and soft tissue infections. Upper extremity deep venous thrombosis (DVT) after PICC placement is a complication with unknown incidence in the orthopaedic literature. The major objectives of this study are Identifying the rate of upper extremity PICC-associated DVTs after orthopaedic procedures;Which orthopaedic subspecialties are most likely to encounter an upper extremity PICC-associated DVT?What surgeries or medical comorbidities are risk factors for upper extremity PICC-associated DVTs?Does type of DVT chemoprophylaxis decrease the risk of an upper extremity PICC-associated DVT?A retrospective review of electronic medical records (EMR) was performed to include all patients undergoing irrigation and debridement (ID) for treatment of orthopaedic surgery-related infections over a 10-year period. All patients with PICC placement were included for analyses. Age, sex, and medical comorbidities were extracted from the EMR. Mann-Whitney non-parametric tests, Fisher's exact tests, Chi-square tests, and Cochran-Mantel-Haenszel (CMH) tests were used to determine associations with DVT events for those with PICCs based on medical comorbidities, PICC lumen size, team placing the PICC, impact of implant removal, and protective effect of DVT chemoprophylaxis. Significance was set at p0.05.Twenty-one of 660 patients (3.18% rate) were found to have an upper extremity PICC-associated DVT. A history of DVT (OR=8.99 [95% CI: 3.39, 49.42]) was significantly associated with an upper extremity PICC-associated DVT. The greatest risk for an upper extremity PICC-associated DVT was intramedullary implant removal (OR=12.43 [95% CI: 3.13, 49.52]). The type of DVT chemoprophylaxis did not significantly affect the likelihood of an upper extremity PICC-associated DVT.Intramedullary implant removal and a history of DVT are risk factors for an upper extremity PICC-associated DVT. The results of this study should be of particular interest to surgeons who do not typically give DVT prophylaxis and plan to perform surgery on patients with CHF, a history of a DVT, or plan to manipulate the intramedullary canal.

Downstream effects of bariatric weight-loss surgery have been associated with bone resorption, potentially jeopardizing total knee arthroplasty (TKA) implant fixation/ingrowth.This case-control study sought to determine if TKA patients with history of bariatric surgery exhibit altered microanatomy of subchondral bone quality in the tibial plateau compared to controls.With IRB approval, 41 bone samples were evaluated from 12 former bariatric surgery patients and 10 sex-, age-, weight-, height-, and BMI-matched controls. Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were completed prior to TKA. Tibial plateau osteochondral tissues were recovered during the TKA procedure, and samples from the medial and lateral plateaus were dissected into 1 × 2 cm sections, scanned using microcomputed tomography (µCT), and plastic-embedded for histologic sectioning/staining of undecalcified bone. Paired t tests with Bonferroni correction were performed to assess group differences.Female bariatric surgery patients had reduced osteoid/total area and greater osteoclast number asymmetry than female controls (p 0.03). No differences were noted in µCT or histologic bone parameters between bariatric and control patients when the sexes were combined. Bariatric patients self-reported worse preoperative PROMIS pain interference and physical function scores than controls (p 0.04).Similarities of subchondral bone between former bariatric surgery patients and matched controls indicate OA disease progression dominates the bone landscape in both patient groups.

Symptomatic disc degeneration is a common cause of low back pain. Recently, the prevalence of low back pain has swiftly risen leading to increased patient disability and loss of work. The increase in back pain also coincides with a rapid rise in patient medical comorbidities. However, a comprehensive study evaluating a link between patient's medical comorbidities and their influence on lumbar intervertebral disc morphology is lacking in the literature.Electronic medical records (EMR) were retrospectively reviewed to determine patient-specific medical characteristics. Magnetic resonance imaging (MRI) was evaluated for lumbar spine intervertebral disc desiccation and height loss according to the Griffith-modified Pfirrmann grading system. Bivariate and multivariable linear regression analyses assessed strength of associations between patient characteristics and lumbar spine Pfirrmann grade severity (Pfirrmann grade of the most affected lumbar spine intervertebral disc) and cumulative grades (summed Pfirrmann grades for all lumbar spine intervertebral discs).In total, 605 patients (304 diabetics and 301 non-diabetics) met inclusion criteria. Bivariate analysis identified older age, diabetes, American Society of Anesthesiologists (ASA) class, hypertension, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, and hypothyroidism as being strongly associated with an increasing cumulative Pfirrmann grades. Multivariable models similarly found an association linking increased cumulative Pfirrmann grades with diabetes, hypothyroidism, and hypertension, while additionally identifying non-white race, heart disease, and previous lumbar surgery. Chronic pain, depression, and obstructive sleep apnea (OSA) were associated with increased Pfirrmann grades at the most affected level without an increase in cumulative Pfirrmann scores. Glucose control was not associated with increasing severity or cumulative Pfirrmann scores.These findings provide specific targets for future studies to elucidate key mechanisms by which patient-specific medical characteristics contribute to the development and progression of lumbar spine disc desiccation and height loss.III (retrospective cohort).

Since the 1970s imaging devices have been rapidly advancing to provide researchers, clinicians, radiologists, and practitioners greater capabilities to image bone. Today, dual-energy X-ray absorptiometry (DXA) has emerged as the gold standard for the assessment of bone and body composition. Despite recent improvements in DXA image quality and reduced radiation dosages and scan times, the data extraction process has yet to be streamlined. The objective of this study was to design an application to allow DXA users to quickly and accurately transfer DXA report data directly into a user-friendly format.Initial development of the DXA Data Xtraction Assistant (DXAManual transcription, by an experienced researcher, took over 10 h with an error rate of 0.6% and average error magnitude of 51%. Data extraction from DXAThe DXA

This study was designed to characterize metabolic responses of meniscal tissue explants to injury and inflammation. We hypothesized that impact injury and interleukin (IL-1β) stimulation of meniscal explants would result in significant increases in matrix metalloproteinase (MMP) activity and relevant cytokine production compared to controls. Mature canine meniscal explants (n = 9/group) were randomly assigned to: (i) IL-1β (0.1 ng/ml) treated (IL); (ii) 25% strain (25); (iii) 75% strain (75); (iv) 25% + IL-1β (25IL); (v) 75% + IL-1β (75IL); or (vi) 0% + no IL-1β control (NC). Explants were impacted at 100 mm/s to 0%, 25%, or 75% strain and then cultured for 12 days with or without 0.1 ng/ml rcIL-1β. Media were refreshed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, GAG, NO, PGE