Search

Background: The purpose of the study was to use Machine Learning (ML) to construct a risk calculator for patients who undergo Total Joint Arthroplasty (TJA) on the basis of New York State Statewide Planning and Research Cooperative System (SPARCS) data and externally validate the calculator on a single TJA center., Methods: Seven ML algorithms, i.e., logistic regression, adaptive boosting, gradient boosting (Xg Boost), random forest (RF) classifier, support vector machine, and single and a five-layered neural network were trained on the derivation cohort. Models were trained on 68% of data, validated on 15%, tested on 15%, and externally validated on 2% of the data from a single arthroplasty center., Results: Validation of the models showed that the RF classifier performed best in terms of 30-d mortality AUROC (Area Under the Receiver Operating Characteristic) 0.78, 30-d readmission (AUROC 0.61) and 90-d composite complications (AUROC 0.73) amongst the test set. Additionally, Xg Boost was found to be the best predicting model for 90-d readmission and 90-d composite complications (AUC 0.73). External validation demonstrated that models achieved similar AUROCs to the test set although variation occurred in top model performance for 90-d composite complications and readmissions between our test and external validation set., Conclusion: This was the first study to investigate the use of ML to create a predictive risk calculator from state-wide data and then externally validate it with data from a single arthroplasty center. Discrimination between best performing ML models and between the test set and the external validation set are comparable., Level of Evidence: III., (© 2023. The Author(s).)

The SARS CoV-2 (COVID-19) pandemic presented unprecedented challenges as communities attempted to respond to the administration of a novel vaccine that faced cold chain logistical requirements and vaccine hesitancy among many, as well as complicated phased rollout plans that changed frequently as availability of the vaccine waxed and waned. The COVID-19 pandemic also disproportionately affected communities of color and communities with barriers to accessing healthcare. In the setting of these difficulties, a program was created specifically to address inequity in vaccine administration with a focus on communities of color and linguistic diversity as well as those who had technological barriers to online sign-up processes common at mass vaccination sites. This effort, the Mobile Vaccine Equity Enhancement Program (MVeeP), delivered over 12,000 vaccines in 24 months through a reproducible set of practices that can inform equity-driven vaccine efforts in future pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Broach, Brown, McEachern, Forget, Lancette, Soucie, Inzerillo, Klugman, Tosi, Haddad, Manor, Bylund, Dellostritto, Grecchi, Camelo, Shirshac, Eshghi, Vega, Hampson, Follwell, Gonzalez, Hicks, McCandless, VanStratten, Botros, Jalbert, Merwin, Schellhammer, Pelto, Rodriguez, LaPriore, Lowell, Radigan, Gull, Gruszecki, Benoit, Dickson and Muller.)

Purpose: Perilunate fracture dislocation (PLFD) injuries are associated with the development of acute carpal tunnel syndrome (CTS). The purpose of our study was to identify the factors that increase the likelihood of developing CTS in patients with PLFD. Additionally, we attempted to classify patients who did not initially undergo carpal tunnel release (CTR) at the time of injury but eventually underwent CTR within the follow-up period., Methods: Patients presenting to a level-1 trauma center with isolated PLFDs (Mayfield III-IV) were retrospectively identified by using CPT and ICD-10 codes. Polytraumatized patients, those with a history of previous wrist trauma, or those with previous carpal tunnel symptoms or surgery were excluded. Outcomes of interest included the development of acute CTS, pre- and post-reduction changes in CTS symptoms, and associated hand and wrist fractures. Chi-square tests, Kruskal-Wallis tests, and multivariate logistic regression were used to examine the predictors of developing CTS after a PLFD., Results: In total, 43 patients were included in the final cohort, with a mean age of 44 years, of which 77% were men. The most common fracture of the carpus included scaphoid fractures (9/43, 21%). The average time from presentation to reduction was 636 minutes. Acute CTS symptoms before reduction were present in 26% of the patients and increased post-reduction to 28%. No difference exists between the time to sedation and the presence of acute carpal tunnel symptoms ( P >.05). During initial surgical intervention, 79% underwent CTR (27/34). Of the seven patients who did not initially undergo a CTR, 57% (4/7) required a CTR within the follow-up period., Conclusion: Reduction of PLFDs did not significantly improve the number of patients with acute CTS. More than 50% of the patients who did not undergo a CTR at the initial surgery required a CTR within the follow-up period., Type of Study/level of Evidence: Prognostic III., (© 2023 The Authors.)

People with a limb loss at the level of the hip or pelvis have the most difficulty returning to walking compared with those with a lower amputation. This is because their prosthesis must replace the hip, knee, and ankle joints. An adjustable hip-disarticulation/hemipelvectomy prosthesis simulator that allows able-bodied individuals to wear and assess a prosthesis can help researchers and manufacturers when designing new prosthetic components (ie, hip joints). SolidWorks computer-aided design software was used to design and simulate an adapter that can connect prosthetic components to an off-the-shelf hip abduction orthosis. The adapter was made of 1020 stainless steel and aluminium 6061-T3 with a yield strength of 276 MPa. To confirm that this adapter is strong and safe for ambulation, mechanical testing was performed using an INSTRON machine. The maximum loads generated in any activity were chosen according to the International Organization for Standardization 15032:2000 standard for hip disarticulation external prostheses. The designed adapter allowed frontal, lateral, or distal mounting of different prosthetic hip joints. Mechanical testing confirmed that the new adapter can withstand forces and moments experienced during ambulation. The hip disarticulation/hemipelvectomy prosthesis simulator is easy to use and adjustable based on each person's height and pelvic width. Furthermore, this simulator would assist rehabilitation practitioners in experiencing the use of hip-level prostheses and give them a better understanding of people using such technologies. The next step in this project is to evaluate able-bodied participant gait while using this hip simulator prosthesis with different hip joints., (Copyright © 2023 International Society for Prosthetics and Orthotics.)

Pyo-pericardium is a collection of purulent fluid in the pericardial sac. It is a rare finding seen in less than 1% of patients who develop acute pericarditis. The condition, though uncommon, has a mortality risk of 100% in untreated patients and 40% in treated patients. Most of the reported cases in the literature describe the occurrence of pyo-pericardium in IV drug users that's secondary to needle fragment embolization to the pericardium diagnosed through an echocardiogram and CT scan with no evidence of bacteremia. Unlike reported cases, we present a case of pyo-pericardium in a 37-year-old woman with bacteremia from a wound infection on her leg secondary to IV drug use. Needle embolization was ruled out in our case as no foreign object was identified on echocardiography or CT scan. Prompt identification followed by aggressive treatment with pericardial window and systemic antibiotics is crucial for decreasing mortality in such high-risk patients., Competing Interests: Conflicts of interest The authors have no financial conflicts to disclose., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Enhanced ion transport is achieved by chemically induced structural distortion.

Competing Interests: Conflict of interest: D.E.J. is a consultant and has IP/royalty rights under Mayo Clinic Ventures with Zimmer Biomet, Inc. The remaining authors have nothing to disclose.

Women with coronary artery disease tend to have a worse short and long-term prognosis relative to men and the incidence of atherosclerotic cardiovascular disease is increasing. Women are less likely to present with classic anginal symptoms when compared with men and more likely to be misdiagnosed. Several non-invasive imaging modalities are available for diagnosing ischemic heart disease in women and many of these modalities can also assist with prognostication and help to guide management. Selection of the optimal imaging modality to evaluate women with possible ischemic heart disease is a scenario which clinicians often encounter. Earlier modalities such as exercise treadmill testing demonstrate significant performance variation in men and women, while newer modalities such as coronary CT angiography, myocardial perfusion imaging and cardiac magnetic resonance imaging are highly specific and sensitive for the detection of ischemia and coronary artery disease with greater parity between sexes. Individual factors, availability, diagnostic performance, and female-specific considerations such as pregnancy status may influence the decision to select one modality over another. Emerging techniques such as strain rate imaging, CT-myocardial perfusion imaging and cardiac magnetic resonance imaging present additional options for diagnosing ischemia and coronary microvascular dysfunction.

Background: Hemophilia carriers experience abnormal bleeding symptoms; however, a lack of awareness about this topic coupled with additional knowledge gaps and barriers leads to suboptimal care for this population., Objective: The primary objective was to describe the current knowledge gaps and challenges from the perspective of both hemophilia carriers and their health care providers., Methods: We carried out a mixed methods descriptive study with two population groups between September and December 2020. The hemophilia carrier perspective was obtained through both focus groups and questionnaires, whereas the health care providers perspective obtained via questionnaire sent to the Association of Hemophilia Care Directors of Canada and the Canadian Association of Nurses in Hemophilia Care. Focus groups were analyzed using descriptive thematic analysis and quantitative survey data was also analyzed., Results: Eleven hemophilia carriers participated along with 19 health care providers (11 physicians, eight nurses). Hemophilia carrier focus group discussions identified four areas representing major challenges or knowledge gaps: (1) negative psychosocial impacts; (2) difficulty determining symptom significance; (3) need for self-advocacy; (4) testing concerns. Survey results from both groups were aligned with the most important topics for ongoing education identified as information on abnormal bleeding symptoms, where to seek treatment, and considerations for heavy menstrual bleeding/menstruation. The majority of both study groups believe obligate or potential carriers should have factor levels checked regardless of age if symptoms of abnormal bleeding occur or before an invasive procedure. However, hemophilia carriers were significantly more in favor of genetic testing under the age of consent than health care providers in all scenarios evaluated., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: The study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients., Methods: We conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls., Results: Among SOT recipients, VE was 29% (95% confidence interval [CI], -19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses., Conclusions: Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses., Competing Interests: Potential conflicts of interest. All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. J. H. K. reports grant support from National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (1K23 AI137321-01A1). M. G. reports grant support from CDC, CDC-Abt, CDC-Westat, and Janssen and a role as the Co-Chair of the Infectious Diseases and Immunization Committee, Texas Pediatric Society, Texas Chapter of American Academy of Pediatrics (AAP). H. K. T. reports a grant from CDC. A. A. G. reports grant support from CDC, NIH, US Department of Defense (DOD), AbbVie, and Faron Pharmaceuticals. T. M. reports payments as a panelist for the Society of Hospital Medicine Updates in Heart Failure (August 25, 2021) and as a board member of the Scott & White Clinic Physicians Board of Directors. D. J. D. reports grant support from NIH/National Institute of General Medical Sciences (T32GM135169). J. D. C. reports grants from the NIH and DOD. K. W. G. reports grant support as a NECTAR Executive Committee member ACTIV-4HT. D. C. F. reports consultant fees from Cytovale and membership on a Medpace Data Safety Monitoring Board (DSMB). D. N. H. reports a contract from CDC and grant support from National Heart, Lung, and Blood Institute (NHLBI) for participation in the ACTIV4d-Host Tissue Trial. M. C. E. reports talks on nutrition in COVID pneumonia at ASPEN conference sponsored by Abbott Laboratories. M. N. G. reports grant support from the CDC, funding from NHLBI and Agency for Healthcare Research and Quality (AHRQ), and fees from Endpoint for participating on a scientific advisory panel, payment for Medicine Grand Rounds at Westchester Medical Center, travel support for attending the ATS Board of Directors meeting, and participation on a DSMB for Regeneron and REPLINISH trial. N. J. J. reports grants from the NIH, DOD, and Medic One Foundation, payment for expert testimony from the Washington Department of Health, participation on DSMBs for Opticyte Inc., Multi-Center, Randomized Control Trial to Study the Effectiveness of Hyperbaric Oxygen for COVID-19 patients with Moderate to Severe Hypoxemia (NCT04619719), and Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot (NCT04265807), and participation as Chair of the ACEP Critical Care Section. I. D. P. reports grants from the CDC, NIH, Janssen Pharmaceuticals, and Intermountain Research & Medical Foundation, institutional fees from Asahi Kasei Pharma and from Regeneron Pharmaceuticals. S. M. B. reports grants from the CDC, NIH, and DOD, fees from Hamilton ventilators for chairing a DSMB, and personal fees from New York University for service on a DSMB. E. T. M. reports a grant from Merck outside the submitted work. A. K. reports grants from the NIH, Ely Lily, United Therapeutics, Johnson & Johnson, BOA Medical, and 4D Medical. A. D. reports funding as the Center PI for PETAL network through NHLBI grant and for participation on a steering committee for ALung technologies. J. G. W. reports grant support from NIH/NHLBI for ACTIV-3 and ACTIV-4 trials and membership on the American Board of Internal Medicine Critical Care Exam Committee. S. Y. C. reports payment as a speaker for La Jolla Pharmaceuticals and consultant fees for PureTech Health and Kiniska Pharmaceuticals. H. M. B. reports grants from the CDC. A. S. L. reports grants from the CDC, NIH, and Burroughs Wellcome Fund, consultant fees from Sanofi, and fees from Roche for membership on a trial steering committee. N. H. reports grants from the CDC, NIH, Sanofi, and Quidel and honoraria for speaking at Continuing Medical Education event at AAP. J. D. C. reports grant support from the CDC. C. G. G. reports consultant fees from Pfizer, Merck, and Sanofi-Pasteur and grants from Campbell Alliance/Syneos Health, CDC, NIH, US Food and Drug Administration, AHRQ, and Sanofi. T. W. R. reports grants from the NIH, DOD, and AbbVie, personal fees from Cumberland Pharmaceuticals as the Director of Medical Affairs, consultant fees from Cytovale, Inc., personal fees from Sanofi, Inc. for serving as a DSMB board member, a role as the Immediate Past President of the American Society of Parenteral and Enteral Nutrition (ASPEN), and stock from Cumberland Pharmaceuticals for consulting work. C J. L. reports grants/contracts from the CDC, NIH, DOD, bioMerieux, Endpoint LLC, Entegrion, Inc., and AbbVie, a patent issued to Cincinnati Children’s Hospital Medical Center for risk stratification in sepsis and septic shock, participation on DSMBS for Study Principal Investigators, roles on the Executive Committee, Immediate Past President, Member, Board of Directors for the Association of Clinical and Translational Science, and stock options in Bioscape Digita. W. H. S. reports grant funding from the CDC for this work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) is a common complication after lung transplantation (LT) and is associated with higher cost and mortality. We sought to evaluate the incidence of postoperative AKI, defined as AKI within 14 days of transplant, and identify associated perioperative factors., Methods: We conducted a single-center, retrospective review of 153 lung transplant recipients. Postoperative AKI was determined using the RIFLE (Risk, Injury, Failure, Loss, End Stage) criteria. Perioperative covariates and their association with postoperative AKI were analyzed using Cox proportional hazards. Kaplan-Meier survival curves were constructed to evaluate patient survival at 1 year and data finalization. A sub-analysis was performed evaluating factors associated with early AKI (within 48 h of transplant) and late AKI., Results: Postoperative AKI occurred in 36.6% of patients with 51.8% of cases occurring within 48 h of LT. Recipient race, transplant type, cardiopulmonary support, and red blood cell administration were associated with postoperative AKI. Survival was significantly lower in patients with postoperative AKI following LT., Conclusions: Postoperative AKI within 2 weeks of lung transplant is associated with lower short- and long-term survival. Perioperative factors associated with postoperative AKI may be potential points of intervention to minimize AKI development in the future., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Samuel M. Brown reports personal fees from Hamilton ventilators, and grants from the National Institutes of Health (NIH) and the U.S. Department of Defense (DoD). Jonathan D. Casey reports grants from the NIH and DoD. Steven Y. Chang was a speaker for La Jolla Pharmaceuticals in 2018, consulted for PureTech Health in 2020, and consulted for Kiniska Pharmaceuticals in December 2021. David J. Douin reports a grant from NIH/National Institute of General Medical Sciences. Abhijit Duggal reports grants from NIH and participation on a Steering Committee for ALung Technologies. Matthew C. Exline reports support from Abbott Labs for sponsored talks. D. Clark Files reports personal consultant fees from Cytovale and membership on a data and safety monitoring board (DSMB) from Medpace. Anne E. Frosch reports grants from NIH/National Institute of Allergy and Infectious Diseases (NIAID), NIH/National Heart, Lung, and Blood Institute (NHLBI), and NIH/INSIGHT/ICC. Manjusha Gaglani reports grants from Abt Associates, Westat, and Janssen. Adit A. Ginde reports grants from NIH, DoD, AbbVie, and Faron Pharmaceuticals. Michelle N. Gong reports grants from NIH and the Agency for Healthcare Research and Quality (AHRQ), and DSMB membership fees from Regeneron, outside the submitted work. Carlos G. Grijalva reports consultancy fees from Pfizer, Merck, and Sanofi-Pasteur; grants from Campbell Alliance/Syneos Health, NIH, the Food and Drug Administration, AHRQ, and Sanofi. David N. Hager reports grants from NIH/NHLBI. Natasha Halasa reports grants and nonfinancial support from Sanofi, and grants from Quidel and NIH. Nicholas J. Johnson reports grants from NIH, DoD, and Medic One Foundation. Akram Khan reports grants from United Therapeutics, Johnson & Johnson, and Eli Lilly. Jennie H. Kwon reports grants from NIH/NIAID. Adam S. Lauring reports personal fees from Sanofi and Roche, and grants from NIH and Burroughs Wellcome Fund. Christopher J. Lindsell reports grants from NIH, DoD, and the Marcus Foundation; contract fees from bioMerieux, Endpoint Health, Entegrion Inc, and AbbVie; and a patent for risk stratification in sepsis and septic shock. Emily T. Martin reports grants from Merck. Arnold S. Monto reports a grant from NIH. Ithan D. Peltan reports grants from NIH, Janssen Pharmaceuticals, and Intermountain Research and Medical Foundation, and institutional support from Asahi Kasei Pharma and Regeneron. Todd W. Rice reports grants from NIH, DoD, and AbbVie and personal fees from Cumberland Pharmaceuticals, Inc., and Cytovale, Inc. No other potential conflicts of interest were disclosed.

Background: Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies., Methods: We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort., Results: The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%-2.32%, P = 5 × 10 -6 ), AMR (2.50%, IQR: 2.06%-3.79%, P = 2 × 10 -5 ), INFXN (0.74%, IQR: 0.46%-1.38%, P = 0.02), and CLAD/NRAD (1.60%, IQR: 0.57%-2.60%, P = 1.4 × 10 -4 ) versus the stable cohort. Area under the receiver operator characteristic curve for AR versus stable was 0.91 (95% confidence interval [CI]: 0.83-0.98). Using a ≥1% dd-cfDNA fraction threshold, sensitivity for AR was 89.1% (95% CI: 76.2%-100.0%), specificity 82.9% (95% CI: 73.3%-92.4%), positive predictive value, 51.9% (95% CI: 37.5%-66.3%), and negative predictive value, 97.3% (95% CI: 94.3%-100%). For combined allograft injury area under the receiver operator characteristic curve was 0.76 (95% CI: 0.66-0.85), sensitivity 59.9% (95% CI: 46.0%-73.9%), specificity 83.9% (95% CI: 74.1%-93.7%), positive predictive value, 43.6% (95% CI: 27.6%-59.6%), and negative predictive value, 91.0% (95% CI: 87.9%-94.0%)., Conclusions: These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study., Competing Interests: A.B., B.G.Z., D.J.R., E.A., G.F., J.S., N.L., M.O., R.S., Z.P.D., Y.-A.C., and P.R.B. are full-time employees at Natera Inc. with stocks or options to own stocks in the company. B.C.K. serves as a consultant to and on the speaker bureau for CareDx, Inc. and has received research funding from CareDx, Natera, and Zambon. J.P.R. has received research funding from Natera. The other authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Study Design: Retrospective analysis., Objective: This study aimed to identify the prevalence of concomitant thoracic spinal and sternal fractures and factors associated with concomitant fractures., Summary of Background Data: The sternum has been implicated in stability of the upper thoracic spine, and both bony structures are included in the stable upper thoracic cage. High force trauma to the thorax can cause multiple fractures to different upper thoracic cage components., Methods: This is a retrospective analysis of electronic medical record data of patients treated at a Level 1 Trauma Center who underwent surgery for thoracic spinal fracture between 2008-2020. We recorded presence of concomitant sternal fracture, injury characteristics, hospital course data, and demographic information., Results: 107 patients with thoracic spinal fractures had a sternal fracture prevalence of 18.7%. The average age was 53.2 [15-90]. 72 (67.3%) were male and 35 (32.7%) were female, 92 (85.9%) were White, 10 (9.3%) were African American, 3 (2.8%) were Hispanic, and 2 (1.9%) were Asian. The average age of patients with sternal fractures was 48.7 years, compared to those without sternal fractures, 54.3 years (P = 0.251). Patients with T1-T7 fractures [14 of 48 (29.2%)] had a significantly higher rate of sternal fractures compared to patients with T8-T12 fractures [6 of 59 (10.2%)] (P = 0.012). Patients with additional rib (P < 0.001), scapula (P = 0.01), clavicle fractures (P = 0.01), and those with multiple other thoracic fractures (P = 0.01) had significantly higher rates of sternal fractures compared to patients without these. Patients with concomitant sternal fractures [10 of 20 (50.0%)] had a significantly higher rate of respiratory complication during their hospital course than patients without concomitant sternal fracture [40 of 87 (46.0%)] (P < 0.001). Sex, age, mechanism of injury, fracture morphology, estimated blood loss during surgery, intraoperative complications, post-surgical intubation status, and post-surgical intubation duration were not associated with sternal fractures., Conclusions: The prevalence of concomitant thoracic spinal fracture and sternal fracture in our series is 18.7%. T1-T7 fractures and presence of rib, scapula, and clavicle fractures were significantly associated with the presence of sternal fractures. Presence of concomitant sternal fracture was significantly associated with respiratory complication during hospital course., Competing Interests: Declaration of Competing Interest None are relevant to this manuscript, Mitchell Breitenbach BS: NONE, Amy Phan, BS: NONE, Mina Botros, MD: NONE, David Paul, MD: NONE, Robert Molinari, MD: NONE, Emmanuel Menga, MD: Consultation fees from Globus and Evolution Spine, Fellowship support: Globus. NONE relevant to this work. Addisu Mesfin, MD: Consultation fees from Depuy and Medtronic. Fellowship support: AO spine .NONE relevant to this work, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Salvia species have a longstanding traditional culinary use, mostly being consumed in the Mediterranean diet as a common herb added to food. Salvia is commonly consumed as a herbal tea for memory enhancement. Alzheimer's disease (AD) is the most prevalent form of dementia affecting people worldwide Therefore, the current research aimed to investigate potential therapeutic benefits of Salvia officinalis (SOL) cultivated in Jordan and Salvia microphylla (SML) cultivated in Egypt with regard to acetylcholinesterase activity, β-amyloid deposition and oxidative stress associated with scopolamine-induced AD. Metabolite profiling of the ethanol extracts of SOL and SML was performed using UPLC-ESI-MS/MS analysis. Methyl carnosate, carnosic acid, carnosol, rosmanol and salvianolic acids were the major secondary metabolites identified in SOL and SML extracts. In our study, scopolamine (1.14 mg kg -1 , i.p.) was administered for 7 consecutive days to induce memory impairment in rats. SML and SOL (150 and 300 mg kg -1 , p.o.) were tested for their effects to reduce the scopolamine-induced deficits. Donepezil (0.5 mg kg -1 , i.p.) was used as a positive control. Scopolamine induced histopathological changes in rats' prefrontal cortex and hippocampus in addition to β-amyloid plaque deposition. Furthermore, scopolamine treatment promoted oxidative stress and acetylcholinesterase activity. On the other hand, treatment with Salvia extracts corrected the histological changes induced by scopolamine and significantly reduced β-amyloid deposition. Moreover, both oxidative stress markers and acetylcholinesterase activity were ameliorated by Salvia treatment. Using virtual docking to the active sites of the human acetylcholinesterase crystal structure, salvianolic acid K, rosmarinic acid and salvianolic acid C showed the best fitting binding modes to active sites of acetylcholinesterase. Accordingly, the present study demonstrates the beneficial effects of Salvia species from Egypt and Jordan against scopolamine-induced AD-like disorder.

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) provide protection against infection with SARS-CoV-2, the virus that causes COVID-19, and are highly effective against COVID-19-associated hospitalization among eligible persons who receive 2 doses (1,2). However, vaccine effectiveness (VE) among persons with immunocompromising conditions* is lower than that among immunocompetent persons (2), and VE declines after several months among all persons (3). On August 12, 2021, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for a third mRNA vaccine dose as part of a primary series ≥28 days after dose 2 for persons aged ≥12 years with immunocompromising conditions, and, on November 19, 2021, as a booster dose for all adults aged ≥18 years at least 6 months after dose 2, changed to ≥5 months after dose 2 on January 3, 2022 (4,5,6). Among 2,952 adults (including 1,385 COVID-19 case-patients and 1,567 COVID-19-negative controls) hospitalized at 21 U.S. hospitals during August 19-December 15, 2021, effectiveness of mRNA vaccines against COVID-19-associated hospitalization was compared between adults eligible for but who had not received a third vaccine dose (1,251) and vaccine-eligible adults who received a third dose ≥7 days before illness onset (312). Among 1,875 adults without immunocompromising conditions (including 1,065 [57%] unvaccinated, 679 [36%] 2-dose recipients, and 131 [7%] 3-dose [booster] recipients), VE against COVID-19 hospitalization was higher among those who received a booster dose (97%; 95% CI = 95%-99%) compared with that among 2-dose recipients (82%; 95% CI = 77%-86%) (p <0.001). Among 1,077 adults with immunocompromising conditions (including 324 [30%] unvaccinated, 572 [53%] 2-dose recipients, and 181 [17%] 3-dose recipients), VE was higher among those who received a third dose to complete a primary series (88%; 95% CI = 81%-93%) compared with 2-dose recipients (69%; 95% CI = 57%-78%) (p <0.001). Administration of a third COVID-19 mRNA vaccine dose as part of a primary series among immunocompromised adults, or as a booster dose among immunocompetent adults, provides improved protection against COVID-19-associated hospitalization., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Samuel M. Brown reports personal fees from Hamilton, institutional fees from Faron Pharmaceuticals and Sedana, grants from Janssen, the National Institutes of Health (NIH), the Department of Defense (DoD), book royalties from Oxford University and Brigham Young University, outside the submitted work. Steven Y. Chang was a speaker for La Jolla Pharmaceuticals in 2018 and consulted for PureTech Health in 2020. James D. Chappell reports grants from NIH during the conduct of the study. Abhijit Duggal reports grants from NIH and participation on a steering committee for ALung Technologies, Inc., outside the submitted work. Matthew C. Exline reports support from Abbott Labs for sponsored talks, outside the submitted work. D. Clark Files reports personal consultant fees from Cytovale and is a data and safety monitoring board (DSMB) member from Medpace, outside the submitted work. Manjusha Gaglani reports grants from CDC-Vanderbilt University Medical Center for the submitted work, CDC-Abt Associates, CDC-Westat, Janssen and Pfizer, outside the submitted work. Adit A. Ginde reports grants from NIH, DoD, AbbVie, and Faron Pharmaceuticals, outside the submitted work. Michelle N. Gong reports grants from NIH and the Agency for Healthcare Research and Quality (AHRQ), DSMB membership fees from Regeneron, outside the submitted work. Carlos G. Grijalva reports consultancy fees from Pfizer, Merck, and Sanofi-Pasteur; grants from Campbell Alliance/Syneos Health, NIH, the Food and Drug Administration, AHRQ, and Sanofi, outside the submitted work. David N. Hager reports salary support from Incyte Corporation and EMPACT Precision Medicine via Vanderbilt University Medical Center and grants from NHLBI, outside the submitted work. Natasha Halasa reports grants and nonfinancial support from Sanofi, and grants from Quidel outside the submitted work. Akram Khan reports grants from United Therapeutics, Johnson & Johnson, Ely Lilly, and GlaxoSmithKline, outside the submitted work. Adam S. Lauring reports personal fees from Sanofi and Roche, outside the submitted work. Christopher J. Lindsell reports grants from NIH, DoD, and the Marcus Foundation; contract fees from bioMerieux, Endpoint LLC, and Entegrion Inc, outside the submitted work; in addition, Dr. Lindsell has a patent for risk stratification in sepsis and septic shock issued. Emily T. Martin reports personal fees from Pfizer and grants from Merck, outside the submitted work. Ithan D. Peltan reports grants from NIH, Janssen Pharmaceuticals and institutional support from Asahi Kasei Pharma and Regeneron, outside the submitted work. Todd W. Rice reports personal fees from Cumberland Pharmaceuticals, Inc, Cytovale, Inc., and Sanofi, Inc., outside the submitted work. Wesley H. Self reports consulting fees from Aeprio Pharmaceuticals and Merck, outside the submitted work. No other potential conflicts of interest were disclosed.

With the increased incidence and survival of lung transplant (LTx) recipients, the risk for chronic sequelae such as chronic kidney disease (CKD) is on the rise. Data on the long-term renal outcome are scarce. We performed a retrospective chart review of 171 adults with LTx from January 1, 2014, to January 1, 2019. Primary outcomes were prevalence of CKD/end-stage renal disease, acute kidney injury (AKI) as a risk factor for future CKD, and all-cause mortality in recipients with CKD compared with the non-CKD group. Secondary outcomes were frequency of utilization of modalities for CKD (urinalysis, imaging, biopsy, nephrology consultations). Baseline median creatinine and estimated glomerular filtration rate (eGFR) were 0.8 mg/dL and 90 mL/min/1.73 m 2 , respectively. Of the participants, 60% (96 of 161), 67% (102 of 153), 79% (37 of 47), 86% (10 of 12) had CKD at the end of 6, 12, 36, and 60 months, respectively, and 16% were on dialysis at the end of the study period; 3% received a subsequent renal transplant, and 27% mortality was noted over a 5-year follow-up period. The odds of CKD development in patients with an AKI during index hospitalization vs no AKI was 6.22 (2.87 to 13.06, P < .0001). The odds ratio of all-cause mortality in patients with CKD compared with non-CKD was 3.36 (95% confidence interval, 1.44-8.64, P = .005). Measurement of hematuria/proteinuria, imaging, and renal biopsy were infrequently used. Given the high prevalence of AKI and CKD in this population, a multidisciplinary team approach with an early nephrology consultation will be key to improve the overall and renal outcomes in LTx recipients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although the global population of people with a hip disarticulation (HD) or hemipelvectomy (HP) amputation is small, the degree of disability is high, affecting function and independence. A comprehensive literature review is needed to examine the evidence for prostheses in these amputation levels., Method: A scoping literature review was conducted to examine related research documents from 1950 to September 2020, found using Scopus, Web of Science, PubMed, and Google Scholar databases. Studies evaluated (retrospectively or prospectively) HD or HP prostheses and were written in English. Study design and protocol, research instrument, sample size, and outcome measures were reviewed., Results: In the past 70 years, 53 articles that evaluated HD or HP prostheses were published. Most research was conducted in the United States (24 articles) and Japan (nine articles). In 42 articles, authors prospectively evaluated the effects of prostheses in these amputation levels. On average, prospective studies had four (SD = 5) participants. Since 1950, only five prospective studies evaluated HD or HP prostheses with 10 or more participants. Moreover, sufficient information was often unavailable for research replication., Conclusion: More evidence is needed regarding the effects of HD or HP prosthetic components (i.e. hip, knee, ankle, socket type, and suspension system) on gait, patient satisfaction, prosthetic use, interface pressure, and energy expenditure. Articles mostly have small sample sizes that reduce confidence in the reliability of their findings and limit generalizability. Future investigations are needed with vigorous methodology and larger sample sizes to provide strong statistical conclusions., (Copyright © 2021 International Society for Prosthetics and Orthotics.)

Background: Outpatient antibiotic prescriptions drive antibiotic overuse in humans, and the Centers for Disease Control and Prevention has identified community pharmacies as potential partners in outpatient stewardship efforts. Clinical decision support (CDS) tools can potentially be used at community pharmacies to aid in outpatient stewardship efforts., Objectives: We sought to determine community pharmacist attitudes toward using a computerized CDS tool to evaluate and manage common complaints and thus promote appropriate antibiotic prescribing., Methods: We conducted in-depth semistructured interviews of community pharmacists to determine attitudes toward using CDS tools in their practice and identify potential barriers in implementation. Thematic analysis was used to identify common themes and subthemes in the pharmacist responses., Results: We interviewed 21 pharmacists and identified 5 themes and 14 subthemes in our interviews. The pharmacists reported that patients frequently presented with complaints of acute infections and that they (the pharmacists) were universally supportive of a CDS intervention that would allow them to assess such patients and, in turn, guide appropriate antibiotic prescribing. They noted that communication difficulties with prescribing physicians and lack of information sharing currently made it difficult to implement stewardship interventions, and they stated that they were interested in any intervention that could help overcome these barriers., Conclusion: Community pharmacies represent an important point of contact for patients and are a potentially valuable setting for outpatient stewardship interventions. Pharmacists were overwhelmingly supportive of using CDS tools to evaluate patients and promote antimicrobial stewardship. These results suggest that it would be feasible to pilot such an intervention in the community pharmacy setting., (Copyright © 2021 American Pharmacists Association®. All rights reserved.)

Study Design: Retrospective cohort study., Objective: To evaluate the diagnostic yield of computed tomography (CT) imaging of the axial skeleton in pediatric patients evaluated a level I trauma center., Summary of Background Data: CT imaging has become ubiquitous in the assessment of axial skeletal injuries in trauma patients., Methods: This is a retrospective study from one Level I trauma center of patients undergoing CT imaging during pediatric trauma assessment. Medical records of pediatric trauma patients 18-year old and younger who underwent axial skeletal CT imaging from 2013 to 2015 were evaluated. The following were assessed: mechanism of injury, age, sex, race/ethnicity, presence of fracture, management of fracture., Results: A total of 831 patients were assessed, there were 355 (42.7%) females and 476 males (57.3%) with an average age of 15.4 (2 mo-18 yrs). 588 (70.8%) were White, 164 (19.7%) were African-American, 12 (1.4%) were Asians, 67 (8.1%) other, and 46 (5.5%) identified as Hispanic. There were 45 patients (5.4%) who sustained 52 fractures. Common mechanisms were motor vehicle accidents (MVA) 28%, sports injuries (18%), and fall from height (15%). 35.9% of fractures were identified on plain radiographs. Nine injuries were treated surgically (one cervical, two thoracic, two lumbar, and four pelvic); three of these were identified on radiographs. From the 14 patients with cervical spine fractures none were detected on radiographs., Conclusion: In this large series of 831 pediatric patients undergoing axial CT imaging, the rate of axial fractures was 5.4%. The majority of these fractures were managed non-surgically. Only 35.9% of fractures were identified on radiographs.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Plant responses to flooding, submergence and waterlogging are important for adaptation to climate change environments. Therefore, the characterization of the molecular mechanisms activated under hypoxic and anoxic conditions might lead to low oxygen resilient crops. Although in mammalian systems prolyl 4 hydroxylases (P4Hs) are involved in the oxygen sensing pathway, their role in plants under low oxygen has not been extensively investigated. In this report, an Arabidopsis AtP4H3 T-DNA knock out mutant line showed higher sensitivity to anoxic treatment possibly due to lower induction of the fermentation pathway genes, ADH and PDC1 , and of sucrose synthases, SUS1 and SUS4 . This sensitivity to anoxia was accompanied by lower protein levels of AGPs-bound epitopes such as LM14 in the mutant line and induction of extensins-bound epitopes, while the expression levels of the majority of the AGPs genes were stable throughout a low oxygen time course. The lower AGPs content might be related to altered frequency of proline hydroxylation occurrence in the p4h3 line. These results indicate active involvement of proline hydroxylation, a post-translational modification, to low oxygen response in Arabidopsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Konkina, Klepadlo, Lakehal, Zein, Krokida, Botros, Iakovidis, Chernobavskiy, Elfatih Zerroumda, Tsanakas, Petrakis, Dourou and Kalaitzis.)

Biliary strictures constitute a major source of morbidity and mortality following liver transplantation (LT). However, studies on the impact of nonanastomotic biliary strictures (NABS) on grafts after LT are limited. 649 patients who underwent LT between January 2013 and June 2017 at our center were retrospectively analyzed and 2.6% (n = 17) of the recipients developed NABS following LT. There were no differences between recipients with and without NABS in indication of LT, graft ischemia time, and type of biliary anastomosis. The incidence of post-LT hepatic artery thrombosis (HAT) (odds ratio [OR]: 15.75, P < .001) and the use of livers from donation after cardiac death (DCD) donors (OR: 8.292, P = .004) were identified as independent significant predictors of NABS by multivariate analysis. Graft survival in those with NABS was significantly worse than in patients without NABS (1-, 3-, and 5-years survival: 64.7%, 57.5%, 0%, vs. 89.8%, 84.0%, 76.4%, P < .001). In conclusion, while the incidence of NABS in our study was relatively low compared to previous reports, NABS was still found to be associated with poor graft survival. Special attention should be paid to NABS occurrence in grafts that develop HAT as well as those from DCD donors.

Surgery involving the use of cardiopulmonary bypass (CPB) has long been associated with cerebral changes and may also contribute to adverse neurocognitive outcomes. However, there is a debate as to whether bypass itself is responsible for these changes. We conducted a systematic literature review on PubMed, supplementing our work with recent articles from other sources to examine the current evidence on neurocognitive decline associated with CPB. While surgeries involving CPB appear to be associated with cerebral changes and potentially with neurocognitive decline, it is unclear as to whether decline is related to the procedure itself. It is possible that the impacts of CPB can be more readily observed among individuals with preoperative cognitive impairment. It is thus important to screen for subtle and more apparent preoperative cognitive impairment as a risk factor for adverse outcomes. Further research, comparing on-pump and off-pump cohorts and involving intensive screening of preoperative cognitive decline, is indicated to elucidate the true neurocognitive consequences of the heart-lung machine., (© 2020 Wiley Periodicals, Inc.)

Introduction: Shoulder arthroplasty (SA) procedures are increasingly performed in the United States. However, there is a lack of data evaluating how patient sex may affect perioperative complications. The purpose of this study was to evaluate sex-based differences in 30-day postoperative complication and readmission rates after SA., Methods: Total SA and reverse SA cases between 2012-2016 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. The 30-day complication rate, readmission rate, operation time, length of stay, and mortality were compared between women and men. Multivariable logistic regression analysis was performed to identify independent perioperative complications associated with patient sex., Results: Of 12,530 SA cases, 6949 (55.4%) were female and 5499 (44.5%) were male. Compared with women, on average men were significantly younger, had lower body mass index, and were less likely to be functionally dependent, and less likely to have an American Society of Anesthesiologists score of 3+ ( P  < .001). Although overall complications and readmission rates between women and men were similar (3.4% vs. 3.7%, P  = .489; 3.0% vs. 2.8%, P  = .497), men were significantly less likely to develop urinary tract infections (UTIs; odds ratio [OR] 0.58, P  = .032) and require transfusions (OR 0.49, P < .001) and had shorter lengths of stay ( P < .001). However, men were significantly more likely to have a superficial surgical site infection (OR 2.63, P  = .035) and 6.8 minute longer operating time ( P < .001) compared with women., Conclusion: Though the overall complication risk is similar between the sexes, their risk profiles are distinct. Men had decreased risk of UTI, blood transfusions, and shorter length of stay but increased risk of surgical site and longer operating time compared with women. This disparity should be discussed when counseling and risk-stratifying patients for SA., (© 2019 The Author(s).)

Background: This study summarizes all literature investigating platelet-rich plasma (PRP) in the treatment of osteoarthritis of the hands and feet., Materials & Methods: This is a PRISMA compliant systematic review of 7 databases and includes a meta-analysis of randomized controlled trial (RCT) data on pain and function., Results: Nine articles were included in the review. Meta-analysis of 4 RCTs shows PRP significantly improves pain and function versus control. More results are significant at longer duration follow-up., Conclusions: PRP improves pain and function of osteoarthritis. Heterogeneity and risk-of-bias limit current data, requiring more RCTs to determine any regenerative potential of PRP., Prospero Systematic Review Registration Number: 136582., Competing Interests: None., (© 2020 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Garnet type solid electrolytes are promising candidates for replacing the flammable liquid electrolytes conventionally used in Li-ion batteries. Al-doped Li 7 La 3 Zr 2 O 12 (LLZO) is synthesized using nebulized spray pyrolysis and field assisted sintering technology (FAST), a novel synthesis route ensuring the preparation of samples with a homogeneous elemental distribution and dense ceramic electrolytes. Ceramic preparation utilizing field assisted sintering, in particular the applied pressure, has significant influence on the material structure, i.e. microstrain, and thereby its electrochemical performance. The phenomenon of microstrain enhancement of electrochemical performance might open a new route towards improved garnet solid electrolytes. A detailed mechanism is proposed for the lattice distortion and resulting microstrain during sintering. The charge transfer resistance of Li-ions at the interface between LLZO and Li is characterized using AC impedance spectroscopy and is amongst the best reported values to date. Additionally, the solid electrolyte is integrated in a full hybrid cell, a practical approach combining all the advantages of the solid electrolyte, while maintaining good contact with the cathode material., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Indications for reverse total shoulder arthroplasty (RTSA) have expanded. The purpose of this retrospective cohort study was to evaluate national trends in shoulder arthroplasty utilization and to compare national perioperative complication rates for hemiarthroplasty (HA), total shoulder arthroplasty (TSA), and RTSA in a matched cohort., Methods: The National Inpatient Sample was queried from 2011-2013 to identify patients who underwent HA, TSA, or RTSA. Age, sex, race, insurance type, Elixhauser comorbidity index, and perioperative complications were identified. A coarsened exact matching algorithm was used to match RTSA patients with TSA and HA patients to compare medical and implant-related perioperative in-hospital complications. Multivariable logistic regression analysis was performed on unmatched data to identify risk factors for development of perioperative complications., Results: Overall, 42,832 shoulder arthroplasties were identified (44% TSAs, 34% RTSAs, 19% HAs). After matching, RTSAs had 6.2 times the odds of a perioperative implant-related complication ( P < .001) and 2 times the odds of a red blood cell transfusion compared with TSAs ( P < .001). The logistic regression model showed that prior shoulder arthroplasty (odds ratio [OR], 15.1; P < .001), younger age (OR, 0.98; P  = .006), earlier year of index surgery (OR, 0.83; P  = .002), history of illicit drug use (OR, 6.2; P  = .008), and depression (OR, 2.3; P  = .003) were risk factors for development of in-hospital implant-related complications after RTSA., Conclusion: The perioperative implant-related complication rate and postoperative transfusion rate of RTSAs were significantly higher than those of TSAs. In addition, prior shoulder surgery, younger age, earlier year of index surgery, history of illicit drug use, and depression were risk factors for implant-related complications after RTSA. However, the perioperative RTSA implant-related complications did decline each year, suggesting a growing national proficiency with performing RTSA.

Background: Pressure injuries (PIs) represent a significant burden on the healthcare system and have a negative impact on the quality of life of those affected by these wounds. Despite best practice guidelines and other protocols to help healthcare facilities prevent PIs, the prevalence of PIs in Canada across all healthcare settings is concerning., Objective: To describe the pattern of PI prevention and identify national priorities and opportunities to address PIs., Methods: A descriptive, cross-sectional, online survey was created between August and December 2017 to explore Canadian healthcare professionals' knowledge, attitudes, and practices related to PIs., Results: In total, 590 surveys were completed. Eighty-five percent of respondents confirmed that PIs occur in their work environments, and 29% claimed PIs are a frequent occurrence. Most of the respondents (91%) confirmed that they were part of a team that treats PIs. Of the 590 participants, 90% confirmed that they are aware of PI prevention devices and technologies. Between 80% and 90% attest to using offloading devices including prophylactic dressings to prevent PIs, but only 20% instituted measures to address moisture-associated skin damage., Conclusions: The findings from this survey have highlighted a disconnect between Canadian healthcare professionals' awareness of PIs and the implementation of best practices for PI prevention. It is evident that, although the majority of respondents were aware of PIs and related treatment protocols, barriers still exist that impede optimized care and treatment.

The treatment planning in radiation therapy (RT) can be arranged to combine benefits of computed tomography (CT) and magnetic resonance imaging (MRI) together to maintain dose calculation accuracy and improved target delineation. Our aim is study the dosimetric impact of uniform relative electron density assignment on IMRT treatment planning with additional consideration given to the effect of a 1.5 T transverse magnetic field (TMF) in MR-Linac. A series of intensity modulated RT (IMRT) plans were generated for two representative tumor sites, pancreas and prostate, using CT and MRI datasets. Representative CT-based IMRT plans were generated to assess the impact of different electron density (ED) assignment on plan quality using CT without the presence of a 1.5 T TMF. The relative ED (rED) values used were taken from the ICRU report 46. Four types of rED assignment in the organs at risk (OARs), the planning target volumes (PTV) and in the non-specified tissue (NST) were considered. Dose was recalculated (no optimization) using a Monaco 5.09.07a research planning system employing Monte Carlo calculations with an option to include TMF. To investigate the dosimetric effect of different rED assignment, the dose-volume parameters (DVPs) obtained from these specific rED plans were compared to those obtained from the original plans based on CT. Overall, we found that uniform rED assignment results in differences in DVPs within 3% for the PTV and 5% for OAR. The presence of 1.5 T TMF on IMRT DVPs resulted in differences that were generally within 3% of the Gold St for both the pancreas and prostate. The combination of uniform rED assignment and TMF produced differences in DVPs that were within 4-5% of the Gold St. Larger differences in DVPs were observed for OARs on T2-based plans. The effects of using different rED assignments and the presence of 1.5 T TMF for pancreas and prostate IMRT plans are generally within 3% and 5% of PTV and OAR Gold St values. There are noticeable dosimetric differences between the CT- and MRI-based IMRT plans caused by a combination of anatomical changes between the two image acquisition times, uniform rED assignment and 1.5 T TMF.

We report the pharmacophore of the peroxisome proliferator-activated receptor δ (PPARδ) agonist natural product phosphoiodyn A is the phosphonate core. Synthesis of simplified phosphonate esters 13 and 15 provide structurally novel, highly selective and potent PPARδ agonists (EC50=78 and 112 nM, respectively). Further, both compounds demonstrate significant neuroprotective activity in an in vitro cellular model indicating that phosphonates may be an effective novel scaffold for the design of therapeutics for the treatment of neurodegenerative disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Onychomycosis is a difficult-to-treat infection whose current treatment paradigm relies primarily on oral antifungals. The emergence of new topical drugs broadens the therapeutic options and prompts a re-evaluation of the current Canadian treatment strategy., Objective: To define a patient-centred Canadian treatment strategy for onychomycosis., Methods: An expert panel of doctors who treat onychomycosis was convened. A systematic review of the literature on treatments for onychomycosis was conducted. Based on the results, a survey was designed to determine a consensus treatment system., Results: First-line therapy should be selected based on nail plate involvement, with terbinafine for severe onychomycosis (>60% involvement), terbinafine or efinaconazole for moderate onychomycosis (20%-60% involvement), and efinaconazole for mild onychomycosis (<20% involvement). Comorbidities, patient preference and adherence, or nail thickness may result in the use of alternative oral or topical antifungals., Conclusion: These guidelines allow healthcare providers and patients to make informed choices about preventing and treating onychomycosis., (© The Author(s) 2015.)

Background: Left atrial appendage (LAA) closure devices have been introduced recently as an alternative for oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF). Because of potential overlap of ablation target areas and the previously implanted LAA closure device, as well as potential complications such as mechanical damage to the device, left atrial (LA) ablation remains a subject of debate in these patients., Objective: We report on the feasibility and clinical efficacy of LA ablation after implantation of LAA closure devices., Methods: Eight patients (6 men; age 69 ± 8 years) with symptomatic paroxysmal AF (n = 5) or persistent AF (mean CHA2DS2-VASc score 3.6 ± 0.7, mean HAS-BLED score 3.6 ± 1.5) and previously implanted WATCHMAN (7 patients) or AMPLATZER Cardiac Plug (1 patient) LAA closure devices received radiofrequency-based LA ablation (4 via circumferential pulmonary vein isolation [CPVI], 4 via CPVI and additional LA linear lesions or complex fractionated atrial electrograms) after a mean of 201 days (range 41-756 days) after LAA closure., Results: Successful LA ablation was achieved without device interference or periprocedural complications. After a mean of 503 days (range 113-1006 days), transesophageal echocardiography (TEE) was performed in all patients to assess for device-related complications. No device dislocation or leakage was observed. In 1 patient (12.5%), a device-related thrombus was found despite therapeutic OAC with dabigatran. Five patients (63%) remained in stable sinus rhythm, and no bleeding events or stroke occurred during a follow-up of 554 days (range 218-1006 days)., Conclusion: LA ablation after LAA closure appears to be feasible. Device-related thrombus formation in 1 patient suggests the need for further TEE examinations after LA ablation after LAA closure device implantation., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Migration of the methylene imidazole side chain in the first reported selective drug-like AT2 receptor agonist C21/M024 (1) delivered the AT2 receptor antagonist C38/M132 (2). We now report that the AT2 receptor antagonist compound 4, a biphenyl derivative that is structurally related to 2, is transformed to the agonist 6 by migration of the isobutyl group. The importance of the relative position of the methylene imidazole and the isobutyl substituent is highlighted herein.

Diabetes mellitus is a serious, life-long condition that is the sixth leading cause of death in North America. Dermatologists frequently encounter patients with diabetes mellitus. Up to 25% of patients with diabetes mellitus will develop diabetic foot ulcers. Foot ulcer patients have an increased risk of amputation and increased mortality rate. The high-risk diabetic foot can be identified with a simplified screening, and subsequent foot ulcers can be prevented. Early recognition of the high-risk foot and timely treatment will save legs and improve patients' quality of life. Peripheral arterial disease, neuropathy, deformity, previous amputation, and infection are the main factors contributing to the development of diabetic foot ulcers. Early recognition of the high-risk foot is imperative to decrease the rates of mortality and morbidity. An interprofessional approach (ie, physicians, nurses, and foot care specialists) is often needed to support patients' needs., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

The management of diabetic foot ulcers can be optimized by using an interdisciplinary team approach addressing the correctable risk factors (ie, poor vascular supply, infection control and treatment, and plantar pressure redistribution) along with optimizing local wound care. Dermatologists can initiate diabetic foot care. The first step is recognizing that a loss of skin integrity (ie, a callus, blister, or ulcer) considerably increases the risk of preventable amputations. A holistic approach to wound assessment is required. Early detection and effective management of these ulcers can reduce complications, including preventable amputations and possible mortality., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

PEP (Peer Education Programme) Talk: Diabetes, Healthy Feet and You is a peer-led self-management programme developed to address the problems of growing prevalence of diabetes and its complications, and limited health care dollars. An evaluation of the programme, how it might be situated within a public health perspective and potential bridges for its implementation in communities throughout Canada and worldwide, are presented. The programme consisted of workshops that were conducted by volunteer peer leaders and health care professionals in 12 communities in 10 Canadian provinces; the volunteers were supported through monthly mentoring teleconferences, on-line tips and discussion board conversations. A web portal was developed to be used by the team, volunteers and community participants. Workshop curriculum was developed based on diabetes footcare and self-management best practise guidelines. Community participants answered pre-and post-workshop statements that indicated that learning occurred, as indicated by an increase in the number of statements answered correctly. Participants' feedback about the workshops was positive. In telephone follow-up interviews, 97% of respondents reported having changed their foot self-management behaviours. The portal was commonly used according to website visits, but not as much as expected for registration of community participants. It is recommended that this programme be made widely available and tailored to the specific needs of the communities and that further evaluation be conducted., (© 2013 The Authors. International Wound Journal © 2013 John Wiley & Sons Ltd and Medicalhelplines.com Inc.)

Care of people with diabetic foot ulcers requires a systematic approach following the wound bed preparation paradigm and the existing best practice recommendations. The purpose of this article is to summarize key evidence and recommendations regarding prevention and management of diabetic foot ulcers that can be translated into practice.

De Ritis described the ratio between the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) almost 50 years ago. While initially described as a characteristic of acute viral hepatitis where ALT was usually higher than AST, other authors have subsequently found it useful in alcoholic hepatitis, where AST is usually higher than ALT. These interpretations are far too simplistic however as acute viral hepatitis can have AST greater than ALT, and this can be a sign of fulminant disease, while alcoholic hepatitis can have ALT greater than AST when several days have elapsed since alcohol exposure. The ratio therefore represents the time course and aggressiveness of disease that would be predicted from the relatively short half-life of AST (18 h) compared to ALT (36 h). In chronic viral illnesses such as chronic viral hepatitis and chronic alcoholism as well as non-alcoholic fatty liver disease, an elevated AST/ALT ratio is predictive of long terms complications including fibrosis and cirrhosis. There are methodological issues, particularly whether or not pyridoxal phosphate is used in the transaminase assays, and although this can have specific effects when patient samples are deficient in this vitamin, these method differences generally have mild effects on the usefulness of the assays or the ratio. Ideally laboratories should be using pyridoxal phosphate supplemented assays in alcoholic, elderly and cancer patients who may be pyridoxine deplete. Ideally all laboratories reporting abnormal ALT should also report AST and calculate the De Ritis ratio because it provides useful diagnostic and prognostic information.

Background and Objectives. Atypical lipomas are uncommon, slow-growing benign tumors. While surgery has been the primary treatment modality, we have managed some patients with radiation (RT) as a component of the treatment and have reported their outcomes in this study. Methods. A retrospective review of all cases of extremity and trunk atypical lipomas in The Sarcoma Database at the study institution was conducted. Results. Thirteen patients were identified. All patients underwent surgical resection at initial presentation and received pre- or postoperative radiation for subtotal resection (n = 2), local recurrence (n = 8), or progressive disease (n = 3). The median total radiation dose was 50 Gy. Median followup was 65.1 months. All patients treated with RT remained free of disease at the last followup. No grade 3 or higher late toxicity from radiation was observed. No cases of tumor dedifferentiation occurred. Conclusion. For recurrent or residual atypical lipomas, a combination of reexcision and RT can provide long-term local control with acceptable morbidity. For recurrent tumors, pre-op RT of 50 Gy appears to be an effective and well-tolerated management approach.

People with diabetes mellitus will develop lower-limb complications, such as neuropathy, peripheral vascular disease, foot ulcers, and lower-leg amputations. Resources to control elevated hemoglobin A1c and blood pressure, along with the standardized approach using the 60-second tool (2012), can detect the high-risk diabetic foot and help prevent complications.

Nonhealing wounds (stalled, healable) challenge affected individuals, wound clinicians, and society. Nonhealing may result despite local factors being corrected. The interplay between tissue degradation, increased inflammatory response, and abundant protease activity is a challenging quandary. A modified Delphi process was utilized to investigate a protease activity test and practice implications.