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The oceans have absorbed nearly half of the fossil-fuel carbon dioxide (C[O.sub.2]) emitted into the atmosphere since pre-industrial times (1), causing a measurable reduction in seawater pH and carbonate saturation [...]

The oceans have absorbed nearly half of the fossil-fuel carbon dioxide (CO2) emitted into the atmosphere since pre-industrial times, causing a measurable reduction in seawater pH and carbonate saturation. If CO2 emissions continue to rise at current rates, upper-ocean pH will decrease to levels lower than have existed for tens of millions of years and, critically, at a rate of change 100 times greater than at any time over this period. Recent studies have shown effects of ocean acidification on a variety of marine life forms, in particular calcifying organisms. Consequences at the community to ecosystem level, in contrast, are largely unknown. Here we show that dissolved inorganic carbon consumption of a natural plankton community maintained in mesocosm enclosures at initial CO2 partial pressures of 350, 700 and 1,050 μatm increases with rising CO2. The community consumed up to 39% more dissolved inorganic carbon at increased CO2 partial pressures compared to present levels, whereas nutrient uptake remained the same. The stoichiometry of carbon to nitrogen drawdown increased from 6.0 at low CO2 to 8.0 at high CO2, thus exceeding the Redfield carbon:nitrogen ratio of 6.6 in today’s ocean. This excess carbon consumption was associated with higher loss of organic carbon from the upper layer of the stratified mesocosms. If applicable to the natural environment, the observed responses have implications for a variety of marine biological and biogeochemical processes, and underscore the importance of biologically driven feedbacks in the ocean to global change. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study., Objectives: Atypical hangman's fractures are associated with increased risk for neurologic injury due to involvement of the posterior cortex of the axis body. We present the largest single-center cohort of atypical hangman's fractures with the goal of guiding treatment decisions and outcomes based on fracture classification., Methods: We performed a retrospective analysis of all patients with atypical hangman's fractures treated at a single Level I trauma center between January 2010 and September 2023. 51 patients met inclusion criteria and demographic, treatment, and radiographic data were recorded and compared across the Type I and II fracture groups., Results: Final treatment modalities varied significantly between the groups ( P < 0.01), with hard cervical collar and invasive halo immobilization being the most prevalent treatments for fracture Types I and II respectively. One Type I fracture patient and four Type II fracture patients failed non-operative treatment, requiring surgery. Across both groups, posterior cervical fusion (73%) was the most common surgical approach. Median length of stay varied significantly between the two fracture groups (2.0 (1.0-7.0) vs 5.0 (3.0-8.0) days; P = 0.01). Irrespective of fracture type, longer hospital length of stay was associated with increased patient age (IRR = 1.02; P < 0.01), non-white race (IRR = 2.47; P = 0.01), injury caused by MVC (IRR = 1.93; P < 0.01), and the presence of non-spine orthopedic injuries (IRR = 1.72; P = 0.03)., Conclusions: While atypical Type I hangman's fractures may be managed effectively non-operatively with a hard cervical collar, atypical Type II fractures managed with a hard cervical collar are at greater risk of requiring subsequent surgical intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background Surgical site infection (SSI) following spine tumor surgery results in delays in radiation therapy and the initiation of systemic treatment. The study aims to assess risk factors for SSI in malignancy-related spinal infections and rates of infection observed in a single center with the use of betadine irrigation (BI) and intrawound vancomycin powder (IVP).  Methods Spine tumor patients managed from 11/2012 to 11/2023 were identified using a surgical database (JotLogs, Efficient Surgical Apps, Portland, Maine). Inclusion criteria were patients receiving BI and IVP and alive at 30 days post-op. Exclusion criteria were patients not receiving a combination of BI and IVP due to allergies and mortality within 30 days of surgery. Patient demographics, histology, history of pre-operative and post-operative radiation treatment history, tumor location, procedure type, number of procedures per patient, SSI, wound culture results, and mortality were collected. Results One hundred two patients undergoing 130 procedures had an SSI rate of 3.85% (5/130). There were 18.6% primary and 81.4% metastatic tumors. Demographics were average age 59.5 years old (range 7-92), 60.8% male, 39.2% female, White 88.2%, Black 9.8%, and others 2%. Pre-operative radiation therapy was significantly associated with the risk of SSI (p=0.005). Percutaneous instrumentation did not lead to a significant difference in infection rates (p=0.139). There was no significant difference in infection rates between primary and metastatic tumors (p=0.58). Multivariable regression analysis revealed pre-operative radiation (OR: 18.1; 95%CI: 1.9-172.7; p=0.009) as the statistically significant independent risk factor. Conclusions Pre-operative radiation therapy remains a risk factor for SSI. However, percutaneous instrumentation did not lead to SSI, and there was no significant difference in infection rates between primary and metastatic tumors. SSI rate was 3.85% in patients who had a combination of BI and IVP in spine tumor surgery., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. University of Rochester Medical Center and MedStar Washington Hospital Center issued approval STUDY00000497 and STUDY00008070. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mesfin et al.)

Aim: To assess the feasibility of Diabetic Foot Care Group (DFCG), a social media-based self-management education and support intervention, for people with diabetes (PWD) empowerment in diabetes-related foot ulceration prevention., Methods: A partially randomized preference trial was conducted among 32 PWD. DFCG was implemented through Facebook. Participants in the intervention group joined the DFCG in addition to their usual care, while the control group received usual care. Data were collected online using questionnaires on participants' DFCG acceptance, engagement and preliminary efficacy on nine diabetes foot care-related outcomes at baseline, one, and three months post-intervention., Results: The participants' study intervention acceptability and engagement rates were 84.2% and 55.2%, respectively. DFCG efficacy rate compared to usual care was 88.9% to 22.2%. Three diabetes foot care-related outcomes increased significantly in the intervention group three-month post-intervention: foot self-care adherence ( p  = 0.001, η p 2  = 0.35), preventive foot self-care practice ( p  = 0.002, η p 2  = 0.33), and physical health status ( p  < 0.02, η p 2  = 0.23)., Conclusion: DFCG is feasible and could effectively improve diabetes foot care-related outcomes., Innovation: Social media is an innovative approach healthcare professionals could utilize to virtually support PWD in ongoing learning and engagement in optimal foot self-care activities., Trial Registration: ClinicalTrials.gov, Identifier: NCT04395521., Competing Interests: The authors declare that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter discussed in this manuscript., (© 2024 The Authors. Published by Elsevier B.V.)

Introduction: Division chiefs play crucial leadership, administrative, and instructive roles within orthopedic subspecialties. The purpose of this study is to investigate the demographic and academic characteristics of division chiefs of adult reconstruction at fellowship institutions in the United States., Methods: Adult reconstruction fellowship programs were identified using the American Association of Hip and Knee Surgeons database. Characteristic information about sex, race, academic rank, additional degrees, fellowship institution, and year of completion were collected. Hirsch indices (h-indices) of the division chiefs were collected from the Scopus database., Results: Of the 120 adult reconstruction fellowship programs identified, 39 had a designated division chief of adult reconstruction. All of the division chiefs were male (n=39). Race breakdown was as follows: 74.4% were White (n=29), 12.8% were Asian (n=5), 7.7% were of mixed ethnicity (n=3), 2.6% were Latinx (n=1), and 2.6% were African American (n=1). The majority (53.8%; n=21) of division chiefs also held the academic rank of professor. The mean time since completion of fellowship was 21.7 ± 8.2 years and the mean h-index of the division chiefs was 24.9 ± 16.2. The fellowship programs that trained the most division chiefs were Massachusetts General Hospital (n=9) and the Hospital for Special Surgery (n=6)., Discussion: Division chiefs of adult reconstruction are integral leaders within their orthopedic subspecialty. An analysis of demographic and educational characteristics revealed a lack of diversity among adult reconstruction division chiefs in the United States. Deliberate efforts to increase the diversity of adult reconstruction leadership must be made to address these disparities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Punreddy et al.)

Introduction: A tibial fracture is an uncommon, yet severe injury that occurs in professional athletes within all major sports leagues. These injuries are often debilitating for professional athletes and can require extensive rehabilitation prior to returning to play. The purpose of this study is to investigate the impact of a tibial fracture on athletic performance in all four major United States sports leagues., Methods: A publicly available professional sports database, Pro Sports Transactions, was queried for tibial injuries from January 01, 2015, to May 31, 2023. The search included all four major U.S. sports leagues. To quantify and compare athletic ability before and after injury, performance-based statistics were collected from standardized player ratings in periods surrounding the date of injury. The percent change in player performance was measured and stratified. The Pearson correlation test was used to analyze player demographics., Results: There were a total of 24 professional athletes who suffered 28 confirmed tibial fractures across all leagues. Upon return, there was a 14.7% decrease in overall player performance across all leagues. National Basketball Association, National Football League, and National Hockey League athletes had a decrease of 34.5%, 29.1%, and 14.2%, respectively, following their return to play. Major League Baseball players demonstrated an 8.1% increase in player performance following their recovery from tibial fracture., Conclusion: Players who suffer tibial fractures often undergo immediate surgery and, in unfortunate cases, may require multiple subsequent procedures. Additionally, athletes spend several months recovering prior to their return. Upon return, athletes' performance may be decreased; however, further study is required to strengthen the association between player performance and tibial fracture recovery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Punreddy et al.)

Hepatic encephalopathy is uncommon in the absence of cirrhosis. We report a 71-year-old woman who presented with altered mental status in the setting of hyperammonemia for the second time in 6 months. Magnetic resonance imaging of the abdomen revealed an uncommon portosystemic shunt involving an enlarged posterior branch of the right portal vein and an accessory right hepatic vein, with no features of cirrhosis. Appropriate management of these patients with ammonia-lowering therapy can reduce repeat episodes and improve quality of life. This case demonstrates the importance of diagnosing non-cirrhotic hepatic encephalopathy in patients with altered mental status., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

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).)

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.)

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.

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.)

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.

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.

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.)

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.

Background: For years, the treatment for invasive lobular carcinoma (ILC) has been mastectomy secondary to the lack of studies investigating the efficacy of breast conservation therapy on patients afflicted with ILC and due to the lack of long-term follow up investigating locoregional recurrence in this patient population. In this article we report the clinical course of a patient diagnosed with ILC., Case Report: We describe the case of a 50-year-old woman with stage IIB (T2N1M0) ER/PR positive right breast ILC who underwent a right modified radical mastectomy, postoperative chemotherapy, a prophylactic left simple mastectomy with bilateral breast reconstruction and tamoxifen. Approximately 12 years later, she presented with a deflated breast implant and recurrent breast cancer with metastatic spread. She received palliative radiotherapy then palliative chemotherapy. Unfortunately, she succumbed to the cancer less than a year after being diagnosed with metastatic disease., Conclusions: This may be the first case report of a ruptured breast implant presenting at the same time as the diagnosis of recurrent breast cancer.

The role of radiotherapy for local control of marginally resected, unresectable, and recurrent giant cell tumors of bone (GCToB) has not been well defined. The number of patients affected by this rare disease is low. We present a series of 58 patients with biopsy proven GCToB who were treated with radiation therapy. A retrospective review of the role of radiotherapy in the treatment of GCToB was conducted in participating institutions of the Rare Cancer Network. Eligibility criteria consisted of the use of radiotherapy for marginally resected, unresectable, and recurrent GCToB. Fifty-eight patients with biopsy proven GCToB were analyzed from 9 participating North American and European institutions. Forty-five patients had a primary tumor and 13 patients had a recurrent tumor. Median radiation dose was 50 Gy in a median of 25 fractions. Indication for radiation therapy was marginal resection in 33 patients, unresectable tumor in 13 patients, recurrence in 9 patients and palliation in 2 patients. Median tumor size was 7.0 cm. A significant proportion of the tumors involved critical structures. Median follow-up was 8.0 years. Five year local control was 85% . Of the 7 local failures, 3 were treated successfully with salvage surgery. All patients who received palliation achieved symptom relief. Five year overall survival was 94%. None of the patients experienced grade 3 or higher acute toxicity. This study reports a large published experience in the treatment of GCToB with radiotherapy. Radiotherapy can provide excellent local control for incompletely resected, unresectable or recurrent GCToB with acceptable morbidity.