Skin sensory alteration and kneeling ability following cruciate retaining total knee arthroplasty are not affected by the incision position: A randomised controlled trial of simultaneous bilateral surgery.

PURPOSE: The purpose of this randomised controlled trial was to assess the impact of skin incision location on the patients' ability to kneel. METHODS: A total of 29 patients undergoing bilateral total knee arthroplasty (58 knees) were randomised to receive a lateral or midline incision, with the contralateral limb receiving the alternative option. Cruciate retaining implants were used in all cases by three experienced arthroplasty surgeons. The primary outcome measures assessed functional ability to kneel using an innovative five-point kneeling scale, preferred knee to kneel on and the area of cutaneous sensory loss around the incision at 6 weeks, 6 months and 12 months. Secondary outcome measures were the OKS, KOOS JR, FJS and EQ5D patient reported outcome measures (PROMS), length of surgical scar, overall knee preference and range of motion (ROM). RESULTS: There were no significant differences between the two groups for any primary or secondary outcome measures. Flexion range however, had a significant positive correlation with kneeling score (r = 0.335, p = 0.010). The kneeling score increased at each time point after surgery and was significantly greater at 12 months than preoperatively (2.7 v 3.5, p = 0.015). The area of sensory loss lateral to the incision was significantly less at 6 and 12 months than at 6 weeks (43.6cm2 and 40.1cm2 v 84.1cm2, p < 0.0001). CONCLUSION: The ability to kneel following cruciate retaining total knee arthroplasty is not affected by the incision position but by time and flexion range. TKA improves the ability to kneel by 12 months post-surgery. Sensory loss lateral to the incision reduces with time. LEVEL OF EVIDENCE: Therapeutic Level 2.

Image-derived instrumentation vs. conventional instrumentation with 3D planning for glenoid component placement in reverse total shoulder replacements: a randomized controlled trial.

Hypothesis: Glenoid baseplate positioning for reverse total shoulder arthroplasty (rTSA) is important for stability and longevity, with techniques such as image-derived instrumentation (IDI) developed for improving implant placement accuracy. We performed a single-blinded randomized controlled trial comparing glenoid baseplate insertion accuracy with 3D preoperative planning and IDI jigs vs. 3D preoperative planning and conventional instrumentation. Methods: All patients had a preoperative 3D computed tomography to create an IDI; then underwent rTSA according to their randomized method. Repeat computed tomography scans performed at six weeks postoperatively were compared to the preoperative plan to assess for accuracy of implantation. Patient-reported outcome measures and plain radiographs were collected with 2-year follow-up. Results: Forty-seven rTSA patients were included (IDI n = 24, conventional instrumentation n = 23). The IDI group was more likely to have a guidewire placement within 2mm of the preoperative plan in the superior/inferior plane (P = .01); and exhibited a smaller degree of error when the native glenoid retroversion was >10° (P = .047). There was no difference in patient-reported outcome measures or other radiographic parameters between the two groups. Conclusion: IDI is an accurate method for glenoid guidewire and component placement in rTSA, particularly in the superior/inferior plane and in glenoids with native retroversion >10°, when compared to conventional instrumentation.

Use of a Commercial 7-T MRI Scanner for Clinical Brain Imaging: Indications, Protocols, Challenges, and Solutions-A Single-Center Experience.

The first commercially available 7-T MRI scanner (Magnetom Terra) was approved by the FDA in 2017 for clinical imaging of the brain and knee. After initial protocol development and sequence optimization efforts in volunteers, the 7-T system, in combination with an FDA-approved 1-channel transmit/32-channel receive array head coil, can now be routinely used for clinical brain MRI examinations. The ultrahigh field strength of 7-T MRI has the advantages of improved spatial resolution, increased SNR, and increased CNR but also introduces an array of new technical challenges. The purpose of this article is to describe an institutional experience with the use of the commercially available 7-T MRI scanner for routine clinical brain imaging. Specific clinical indications for which 7-T MRI may be useful for brain imaging include brain tumor evaluation with possible perfusion imaging and/or spectroscopy, radiotherapy planning; evaluation of multiple sclerosis and other demyelinating diseases, evaluation of Parkinson disease and guidance of deep brain stimulator placement, high-detail intracranial MRA and vessel wall imaging, evaluation of pituitary pathology, and evaluation of epilepsy. Detailed protocols, including sequence parameters, for these various indications are presented, and implementation challenges (including artifacts, safety, and side effects) and potential solutions are explored.

Patient-reported outcome measures for patellofemoral disorders: a systematic review.

INTRODUCTION: Patellofemoral conditions include, but are not limited to, anterior knee pain syndrome and patellar instability. Patients and surgeons may find it difficult to identify the specific source of the symptoms and clinical scenarios, so patient-reported outcome measures (PROMs) may be a useful diagnostic aid. There are a number of available PROMs for patellofemoral conditions, which are often used indistinctly. This systematic review explores the available PROMs for patellofemoral conditions, their use and methodological quality. METHODS: A systematic review was conducted, searching for scientific articles relating to PROMs in patellofemoral conditions, from inception to July 2022. Scoring systems including physician-directed or imagining assessment were not included. All types of conditions in the patellofemoral joint were considered. RESULTS: Twenty-two relevant PROMs were encountered, divided into four categories: eight PROMs for anterior knee pain syndrome, five for patellar instability, four for other patellofemoral conditions and five for non-specific PROMs. CONCLUSIONS: While many PROMs have been found used in patellofemoral research, only few of them have showed sufficient methodological quality. In addition, PROMs employed in PF literature are often inaccurately chosen. This review may help authors to better understand the characteristics of specific patellofemoral PROMs, in order to select the more appropriate and recommended ones. LEVEL OF EVIDENCE: Level II.

The efficacy of topical preparations in reducing the incidence of Cutibacterium acnes at the start and conclusion of total shoulder arthroplasty: a randomized controlled trial.

BACKGROUND: Preoperative skin preparations for total shoulder arthroplasty (TSA) are not standardized for Cutibacterium acnes eradication. Topical benzyl peroxide (BPO) and benzyl peroxide with clindamycin (BPO-C) have been shown to reduce the bacterial load of C acnes on the skin. Our aim was to investigate whether preoperative application of these topical antimicrobials reduced superficial colonization and deep tissue inoculation of C acnes in patients undergoing TSA. METHODS: In a prospective, single-blinded randomized controlled trial, 101 patients undergoing primary TSA were randomized to receive either topical pHisoHex (hexachlorophene [1% triclosan; sodium benzoate, 5 mg/mL; and benzyl alcohol, 5 mg/mL]) (n = 35), 5% BPO (n = 33), or 5% BPO with 1% clindamycin (n = 33). Skin swabs obtained prior to topical application and after topical application before surgery, as well as 3 intraoperative swabs (dermis after incision, on joint capsule entry, and dermis at wound closure), were cultured. The primary outcome was positive culture findings and successful decolonization. RESULTS: All 3 topical preparations were effective in decreasing the rate of C acnes. The application of pHisoHex reduced skin colonization by 50%, BPO reduced skin colonization by 73.7%, and BPO-C reduced skin colonization by 81.5%. The topical preparation of BPO-C was more effective in decreasing the rate of C acnes at the preoperative and intraoperative swab time points compared with pHisoHex and BPO (P = .003). Failure to eradicate C acnes with topical preparations consistently resulted in deep tissue inoculation. There was an increase in the C acnes contamination rate on the skin during closure (33%) compared with skin cultures taken at surgery commencement (22%). CONCLUSION: Topical application of BPO and BPO-C preoperatively is more effective than pHisoHex in reducing colonization and contamination of the surgical field with C acnes in patients undergoing TSA.

Intraosseous Regional Prophylactic Antibiotics Decrease the Risk of Prosthetic Joint Infection in Primary TKA: A Multicenter Study.

BACKGROUND: Recent studies have demonstrated that the administration of regional prophylactic antibiotics by intraosseous (IO) injection achieves tissue concentrations around the knee that are 10- to 15-fold higher than intravenous (IV) delivery of prophylactic antibiotics. It is currently unknown whether the use of regional prophylactic antibiotics for primary TKA would result in a lower risk of prosthetic joint infection (PJI). QUESTIONS/PURPOSES: (1) Is IO injection of prophylactic antibiotics associated with a decreased risk of early (< 12 months) deep PJI compared with traditional IV prophylactic antibiotics? (2) What other patient factors are associated with an increased risk of early PJI after TKA, and do regional prophylactic antibiotics influence these risk factors? (3) Can IO antibiotics be administered to all patients, and what complications occurred from the delivery of IO prophylactic antibiotics? METHODS: A retrospective comparative study of all primary TKAs (1909 TKAs) over a 5-year period (January 2013 to December 2017) was performed to determine the risk of early PJI. Three primary TKAs did not meet the study inclusion criteria and were excluded from the study, leaving a total of 1906 TKAs (725 IO, 1181 IV) for analysis at a minimum of 12 months after index procedure. Both cohorts exhibited similar ages, BMI, and American Society of Anesthesiologists (ASA) grades; however, a greater proportion of patients in the IO cohort were smokers (p = 0.01), while a greater proportion of patients were diabetic in the IV cohort (p = 0.006). The PJI risk between IO and IV delivery techniques was compared while adjusting for patient demographics and medical comorbidities. Complications related to IO delivery-inability to administer via IO technique, compartment syndrome, fat embolism, and red man syndrome with vancomycin use-were recorded. RESULTS: The delivery of regional prophylactic antibiotics by the IO technique resulted in a lower PJI risk than IV prophylactic antibiotics (0.1% [1 of 725] compared with 1.4% [16 of 1181]; relative risk 0.10 [95% CI 0.01 to 0.77]; p = 0.03). BMI (ß = -0.17; standard error = 0.08; p = 0.02), diabetes (ß = -1.80; standard error = 0.75; p = 0.02), and renal failure (ß = -2.37; standard error = 0.84; p = 0.01) were factors associated with of PJI, while smoking, sex, and ASA score were not contributing factors (p > 0.05). Although BMI, diabetes, and renal failure were identified as infection risk factors, the use of IO antibiotics in these patients did not result in a lower PJI risk compared with IV antibiotics (p > 0.05). IO antibiotics were able to be successfully administered to all patients in this cohort, and there were no complications related to the delivery of IO antibiotics. CONCLUSION: Surgeons should consider administering regional prophylactic antibiotics in primary TKA to reduce the risk of early PJI. Future randomized prospective clinical trials are needed to validate the efficacy of regional prophylactic antibiotics in reducing the PJI risk in primary TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Orthopaedic patients underestimate their body weight too: a cross-sectional study.

INTRODUCTION: The relation between a large body mass and comorbidity, certain types of cancers and musculoskeletal disorders has been extensively documented. However, a high proportion of overweight patients appears unaware of the medical risks of their condition and frequently underestimates their body weight. This observation is prevalent across numerous medical specialties and settings. METHODS: This study analysed the misperception of obesity status in a cohort of 1137 patients attending an orthopaedic clinic by means of self-completed questionnaires and objective biometrics. RESULTS: Patients displayed a poor estimation of the self-body mass index (34.6%), especially among larger individuals, with 45.15% of pre-obese and 21.17% of obese patients previously attempting weight-loss. A direct association between low educational achievement and obesity rates was observed in orthopaedic patients. DISCUSSION: Obesity is a well-known contributor to many conditions, including musculoskeletal diseases. Despite this association, many obese patients consider their body mass as normal. Misperception of self-body weight has been documented in many medical specialities, and this study confirms the same scenario in orthopaedic patients. CONCLUSION: The association between self-image distortion and obesity observed in this study may assist in the evaluation and management of obesity cases in orthopaedic clinics.

The Protective Effect of Estrogen Against Radiation Cataractogenesis is Dependent Upon the Type of Radiation.

Astronauts participating in prolonged space missions constitute a population of individuals who are at an increased risk for cataractogenesis due to exposure to densely ionizing charged particles. Using a rat model, we have previously shown that after irradiation of eyes with either low-linear energy transfer (LET) 60Co γ rays or high-LET 56Fe particles, the rate of progression of anterior and posterior subcapsular cataracts was significantly greater in ovariectomized females implanted with 17-ß-estradiol (E2) compared to ovariectomized or intact rats. However, our additional low-LET studies indicated that cataractogenesis may be a modifiable late effect, since we have shown that the modulation of cataractogenesis is dependent upon the timing of administration of E2. Interestingly, we found that E2 protected against cataractogenesis induced by low-LET radiation, but only if administered after the exposure; if administered prior to and after irradiation, for the entire period of observation, then E2 enhanced progression and incidence of cataracts. Since most radioprotectors tested to date are unsuccessful in protecting against the effects of high-LET radiation, we wished to determine whether the protection mediated by E2 against radiation cataractogenesis induced by low-LET radiation would also be observed after high-LET irradiation. Female 56-day-old Sprague-Dawley rats were treated with E2 at various times relative to the time of single-eye irradiation with 2 Gy of 56Fe ions. We found that administration of E2 before irradiation and throughout the lifetime of the rat enhanced cataractogenesis compared to ovariectomized animals. The enhancing effect was slightly reduced when estrogen was removed after irradiation. However, in contrast to what we observed after γ-ray irradiation, there was no inhibition of cataractogenesis if E2 was administered only after 56Fe-ion irradiation. We conclude that protection against cataractogenesis by estrogen is dependent upon the type and ionization density of radiation that the lens was exposed to. The lack of inhibition of radiation cataractogenesis in rats that receive E2 treatment after high-LET irradiation may be attributed to the qualitative differences in the types of DNA damage induced with high-LET radiation compared to low-LET radiation or how damage may be modified at the DNA or tissue level after irradiation.

Computer-Assisted Technologies in Arthroplasty: Navigating Your Way Today.

Computer-assisted technologies that are used in arthroplasty include navigation, image-derived instrumentation (IDI), and robotics. Computer-assisted navigation improves accuracy and allows for real-time assessment of component positioning and soft-tissue tension. It is not clear whether the implementation of these technologies improves the clinical outcome of surgery. High cost and time demands have prevented the global implementation of computer-assisted technologies.

Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus.

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.

Dynamic Evaluation of Patellofemoral Instability: A Clinical Reality or Just a Research Field? A Literature review.

Patellofemoral instability (PFI) is one of the most disabling conditions in the knee, often affecting young individuals. Despite its not uncommon presentation, the underlying biomechanical features leading to this entity are not entirely understood. The suitability of classic physical examination manoeuvres and imaging tests is a matter of discussion among treating surgeons, and so are the findings provided by these means. A potential cause for this lack of consensus is the fact that, classically, the diagnostic approach for PFI has relied on statically obtained data. Many authors advocate for the study of this entity in a dynamic scenario, closer to the actual situation in which the instability episodes occur. In this literature review, we have compiled the available data from the last decades regarding dynamic evaluation methods for PFI and related conditions. Several categories are presented, grouping the related techniques and devices: physical examination, imaging modalities (ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT) and combined methods), arthroscopic evaluation, and others. In conclusion, although a vast number of quality studies are presented, in which comprehensive data about the biomechanics of the patellofemoral joint (PFJ) are described, this evidence has not yet reached clinical practice universally. Most of the data still stays in the research field and is seldom employed to assist a better understanding of the PFI cases and their ideal treatment targets.

Experimental model of peri-prosthetic infection of the knee caused by Staphylococcus aureus using biomaterials representative of modern TKA.

Prosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains the leading cause for revision surgery, with Staphylococcus aureus the bacterium most frequently responsible. We describe a novel rat model of implant-associated S. aureus infection of the knee using orthopaedic materials relevant to modern TKA. Male Sprague-Dawley rats underwent unilateral knee implant surgery, which involved placement of a cementless, porous titanium implant into the femur, and an ultra-highly cross-linked polyethyelene (UHXLPE) implant into the proximal tibia within a mantle of gentamicin-laden bone cement. S. aureus biofilms were established on the surface of titanium implants prior to implantation into the femur of infected animals, whilst control animals received sterile implants. Compared to controls, the time taken to full weight-bear and recover pre-surgical body weight was greater in the infected group. Neutrophils and C-reactive protein levels were significantly higher in infected compared to control animals at day 5 post surgery, returning to baseline levels for the remainder of the 28-day experimental period. Blood cultures remained negative and additional plasma inflammatory markers were comparable for control and infected animals, consistent with the clinical presentation of delayed-onset PJI. S. aureus was recovered from joint tissue and implants at day 28 post surgery from all animals that received pre-seeded titanium implants, despite the use of antibiotic-laden cement. Persistent localised infection was associated with increased inflammatory responses and radiological changes in peri-implant tissue. The availability of a preclinical model that is reproducible based on the use of current TKA materials and consistent with clinical features of delayed-onset PJI will be valuable for evaluation of innovative therapeutic approaches.

Absence of cytotoxic and inflammatory effects following in vitro exposure of chondrogenically-differentiated human mesenchymal stem cells to adenosine, lidocaine and Mg2+ solution.

BACKGROUND: ALM solution, a combination of adenosine, lidocaine and Mg2+, is an emerging small volume therapy that has been shown to prevent and correct coagulopathy and surgery-related inflammation in preclinical models, though its application in orthopaedic surgery is yet to be demonstrated. The effect of ALM solution on chondrocytes is unknown. The aim of this preliminary study was to investigate the effect of ALM solution on viability and inflammatory responses of chondrogenically-differentiated human bone marrow-derived mesenchymal stem cells (chondro-MSC), in vitro. METHODS: Chondro-MSC were exposed to media only, saline (0.9% NaCl or 1.3% NaCl) only, or saline containing ALM (1 mM adenosine, 3 mM lidocaine, 2.5 mM Mg2+) or tranexamic acid (TXA, 100 mg/ml) for 1 or 4 h. Responses to ALM solutions containing higher lidocaine concentrations were also compared. Chondrocyte viability was determined using WST-8 colorimetric assays and inflammatory cytokine (TNF-α, IL-1ß, IL-8) and matrix metalloproteinases (MMP-3, MMP-12, MMP-13) concentrations using multiplex bead arrays. RESULTS: The viability of chondro-MSC was significantly greater after 1 h treatment with ALM compared to saline (96.2 ± 7.9 versus 75.6 ± 7.3%). Extension of exposure times to 4 h had no significant adverse effect on cell viability after treatment with ALM (1 h, 85.4 ± 5.6 v 4 h, 74.0 ± 15.2%). Cytotoxicity was evident following exposure to solutions containing lidocaine concentrations greater than 30 mM. There were no significant differences in viability (80 ± 5.4 v 57.3 ± 16.2%) or secretion of IL-8 (60 ± 20 v 160 ± 50 pg/ml), MMP-3 (0.95 ± 0.6 v 3.4 ± 1.6 ng/ml), and MMP-13 (4.2 ± 2.4 v 9.2 ± 4.3 ng/ml) in chondro-MSC exposed to saline, ALM or TXA. CONCLUSIONS: Short-term, in vitro exposure to clinically-relevant concentrations of ALM solution had no adverse inflammatory or chondrotoxic effects on human chondro-MSC, with responses comparable to saline and TXA. These findings provide support for continued evaluation of ALM solution as a possible therapeutic to improve outcomes following orthopaedic procedures.

Evaluation of Bacteriophage Anti-Biofilm Activity for Potential Control of Orthopedic Implant-Related Infections Caused by Staphylococcus aureus.

BACKGROUND: Despite significant advancements in surgical protocols and biomaterials for orthopedics, peri-prosthetic joint infection (PJI) remains a leading cause of implant failure. Staphylococcus aureus nasal colonization is an established risk factor for PJI, with methicillin-sensitive S. aureus a leading cause of orthopedic implant-related infections. The purpose of these in vitro studies was to investigate the antibacterial activity of a tailored bacteriophage cocktail against planktonic and biofilm-associated S. aureus. METHODS: The S. aureus strains (n = 30) were screened for their susceptibility to a library of S. aureus-specific bacteriophage (n = 31). Five bacteriophage preparations that demonstrated bactericidal activity against >90% of S. aureus strains tested were combined as a StaPhage cocktail and assessed for their antibacterial activity toward planktonic and biofilm-associated S. aureus, with biofilms established on three-dimensional-printed porous titanium scaffolds. RESULTS: StaPhage treatment immediately after bacterial inoculation inhibited growth of S. aureus by >98% in eight hour cultures when multiplicity of infection of phages to bacteria was greater than 1:1 (p < 0.01). Viable bacterial numbers within biofilms on titanium surfaces were significantly reduced (6.8 log10 to 6.2 log10 colony forming units [CFU]; p < 0.01) after exposure to the StaPhage cocktail, in vitro. No significant reduction was observed in biofilms exposed to 100 times the minimal inhibitory concentration of cefazolin (log10 6.81 CFU). CONCLUSIONS: Combined, these data demonstrate the in vitro efficacy of S. aureus-specific bacteriophage cocktails against S. aureus growing on porous titanium and warrant further in vivo studies in a clinically relevant animal model to evaluate the potential application of bacteriophage in the management of PJI caused by S. aureus.

Early results of medial opening wedge high tibial osteotomy using an intraosseous implant with accelerated rehabilitation.

BACKGROUND: Accelerated rehabilitation protocols for medial opening wedge high tibial osteotomy (MOW HTO) using intraosseous implants have not previously been described. The present study provides early clinical and radiological outcomes of MOW HTO using a polyetheretherketone (PEEK) intraosseous system, in combination with an early weight-bearing protocol. METHODS: Twenty consecutive knees (17 patients) underwent navigated MOW HTO using a PEEK implant with accelerated rehabilitation. Time to union and maintenance of correction were assessed radiographically for 12 months post-operative. Patient outcomes were monitored for a mean follow-up of 38 months (range 23-42) using standardised instruments (WOMAC, IKDC and Lysholm scores). RESULTS: All knees were corrected to valgus. The mean time to unassisted weight-bearing was 55 days (SD 24, range 21-106). Bone union occurred in 95% of knees by 6 months, with correction maintained for 15 knees at 12 months post-operative. Knees for which correction was lost within 1 year of surgery had significantly greater preoperative varus alignment. Implant survivorship was 95% and 80% at 12 and 38 months post-operative, respectively. Significant improvements in patient-reported satisfaction, knee function and return to daily activities from preoperative to 38 months post-operative were reported (WOMAC 36 v 0; IKDC 35.6 v 96; Lysholm 44.5 v 100). CONCLUSIONS: Accelerated rehabilitation following MOW HTO with an intraosseous PEEK implant did not delay bone union, with significantly improved functional outcomes within 3 months post-operative. Early findings suggest that this approach may be suitable for a defined patient subset, with consideration for the extent of preoperative genu varum.

Mediating effects of body mass index, physical activity, and emotional distress on the relationship between short sleep and cardiovascular disease.

The current study investigated the mediating effects of body mass index (BMI), physical activity, and emotional distress on the association between short sleep duration (<7 hours per 24-hour period) and cardiovascular disease (CVD) and risk factors.We used data from the National Health Interview Survey, an ongoing nationally representative cross-sectional study of noninstitutionalized US adults (≥18 years) from 2004 to 2013 (N = 206,049). Participants provided information about anthropometric features (height and weight), sociodemographic factors, health behaviors (smoking and physical activity), emotional distress, and physician-diagnosed health conditions, including hypertension, coronary heart disease, diabetes, heart attack, stroke, kidney disease, and cancer. Structural equation modeling was used to assess the mediating effects of physical activity, BMI, and emotional distress on the relationship between short sleep and CVDs and risk factors (coronary heart disease, hypertension, diabetes, chronic kidney disease, heart attack, and stroke).Of the sample, 54.7% were female, 60.1% identified as white, 17.7% as Hispanic, and 15.4% as black. The mean age of the respondents was 46.75 years (SE = 0.12), with a mean BMI of 27.11 kg/m (SE = 0.02) and approximately 32.5% reported short sleep duration. The main relationship between short sleep and CVD and risk factors was significant (ß = 0.08, P < .001), as was the mediated effect via BMI (indirect effect = 0.047, P < .001), emotional distress (indirect effect = 0.022, P < .001), and physical activity (indirect effect = -0.022, P = .035), as well as after adjustment for covariates, including age, race, sex, marital status, and income: short sleep and CVD (B = 0.15; SE = 0.01; P < .001), BMI (B = 0.05; SE = 0.00; P < .001), emotional distress (B = 0.02; SE = 0.00; P < .001), and physical activity (B = 0.01; SE = 0.00; P < .001).Our findings indicate that short sleep is a risk factor for CVD and that the relationship between short sleep and CVD and risk factors may be mediated by emotional distress and obesity, and negatively mediated by physical activity.

Use of regional administration of prophylactic antibiotics in total knee arthroplasty.

Prosthetic joint infection after total knee arthroplasty is an infrequent, yet serious complication. Antimicrobial prophylaxis plays an important role in reducing the rate of surgical site infections. To be effective as an antimicrobial prophylaxis, the serum, tissue and bone concentrations of the antibiotic must be greater than the target organism's minimum inhibitory concentration. As antibiotic resistance increases current intravenous prophylactic dosing has been shown to be subtherapeutic for some patients. Intravenous regional administration and intraosseous regional administration of prophylactic antibiotics are novel methods used to increase the antibiotic tissue concentrations, which may enhance the efficacy of prophylactic antibiotics in total knee arthroplasty. Currently, literature has shown both intravenous regional administration and intraosseous regional administration to be safe and effective techniques. However, there is no clinical evidence to show that it results in a reduction of prosthetic joint infection rates. This study summarizes the current knowledge base on the use of regional administration of prophylactic antibiotics in total knee arthroplasty.

Tranexamic acid is associated with selective increase in inflammatory markers following total knee arthroplasty (TKA): a pilot study.

BACKGROUND: Tranexamic acid (TXA) is commonly used in orthopedic surgery to reduce excessive bleeding and transfusion requirements. Our aim was to examine if TXA was required in all osteoarthritis patients undergoing TKA surgery, and its possible effects on systemic inflammation and coagulation properties. METHODS: Twenty-three patients (Oxford Score 22-29) were recruited consecutively; 12 patients received TXA before (IV, 1.2 g/90 kg) and immediately after surgery (intra-articular, 1.4 g/90 kg). Inflammatory mediators and ROTEM parameters were measured in blood at baseline, after the first bone-cut, immediately after surgery, and postoperative days 1 and 2. RESULTS: After the bone cut and surgery, TXA significantly increased MCP-1, TNF-α, IL-1ß and IL-6 levels compared to non-TXA patients, which was further amplified postoperatively. During surgery, TXA significantly prolonged EXTEM clot times, indicating a thrombin-slowing effect, despite little or no change in clot amplitude or fibrinogen. TXA was associated with three- to fivefold increases in FIBTEM maximum lysis (ML), a finding counter to TXA's antifibrinolytic effect. Maximum lysis for extrinsic and intrinsic pathways was < 8%, indicating little or no hyperfibrinolysis. No significant differences were found in postoperative hemoglobin between the two groups. CONCLUSIONS: TXA was associated with increased systemic inflammation during surgery compared to non-TXA patients, with further amplification on postoperative days 1 and 2. On the basis of little or no change in viscoelastic clot strength, fibrinogen or clot lysis, there appeared to be no clinical justification for TXA in our group of patients. Larger prospective, randomized trials are required to investigate a possible proinflammatory effect in TKA patients.

Determination of the Accuracy of Navigated Kinematic Unicompartmental Knee Arthroplasty: A 2-Year Follow-Up.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) lacks history of patient satisfaction and research addressing technique validity. The aim of this study was to determine minimally invasive navigated kinematic UKA accuracy by comparing postoperative limb alignment with preoperative stress values. METHODS: A single-center retrospective study was conducted on 53 consecutive patients (postoperative alignment: varus n = 51, valgus n = 2) who underwent computer navigation assisted UKA. Two patient groups (A and B) predetermined by joint deformity cut-off points (B included valgus deformity) underwent preoperative magnetic resonance imaging and x-ray evaluation to assess limb alignment and exclude lateral and patellofemoral osteoarthritis. Preoperative and postoperative joint alignment, stress value, and range of movement were recorded with navigation. Outcome measures include comparison of postoperative alignment to the preoperative stress values for varus and valgus postoperative alignment groups and preoperative and/or postoperative Western Ontario and McMaster Universities and Knee Society Score evaluations. RESULTS: Minor systematic bias was found between stress value and postoperative alignment; however, the magnitude of difference was clinically acceptable. Score evaluations, prosthesis size or alignment didn't differ between groups. Furthermore, there was no significant increase in range of movement at 2 years. There was a high degree of agreement between stress value and postoperative alignment values suggesting strong validity for the surgical technique to determine optimal postoperative alignment. CONCLUSION: This study validates our surgical technique. Minimally invasive navigated UKA allows us to predict predisease alignment and recreates it with high accuracy. Our clinical results at 2 years are comparable with other published data.

Tissue Transglutaminase Activates Cancer-Associated Fibroblasts and Contributes to Gemcitabine Resistance in Pancreatic Cancer.

Resistance to chemotherapy is a hallmark of pancreatic ductal adenocarcinoma (PDA) and has been partly attributed to the dense desmoplastic stroma, which forms a protective niche for cancer cells. Tissue transglutaminase (TG2), a Ca2+-dependent enzyme, is secreted by PDA cells and cross-links proteins in the tumor microenvironment (TME) through acyl-transfer between glutamine and lysine residues, promoting PDA growth. The objective of the current study was to determine whether secreted TG2 by PDA cells alters the response of pancreatic tumors to gemcitabine. Orthotopic pancreatic xenografts and co-culture of PDA and stromal cells were employed to determine the mechanisms by which TG2 alters tumor-stroma interactions and response to gemcitabine. Analysis of the pancreatic The Cancer Genome Atlas (TCGA) database demonstrated that increased TG2 expression levels correlate with worse overall survival (hazard ratio=1.37). Stable TG2 knockdown in PDA cells led to decreased size of pancreatic xenografts and increased sensitivity to gemcitabine in vivo. However, TG2 downregulation did not increase cytotoxicity of gemcitabine in vitro. Additionally, multivessel density and gemcitabine uptake in pancreatic tumor tissue, as measured by mass spectrometry (MS-HPLC), were not significantly different in tumors expressing TG2 versus tumors in which TG2 was knocked down. Fibroblasts, stimulated by TG2 secreted by PDA cells, secrete laminin A1, which protects cancer cells from gemcitabine-induced cytotoxicity. In all, our results demonstrate that TG2 secreted in the pancreatic TME orchestrates the cross talk between cancer cells and stroma, impacting tumor growth and response to chemotherapy. Our study supports TG2 inhibition to increase the antitumor effects of gemcitabine in PDA.