Managing the Physiologically Difficult Airway in Critically Ill Adults.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

Extreme material parameters accessible by active acoustic metamaterials with Willis coupling.

Active acoustic metamaterials incorporate electric circuit elements that input energy into an otherwise passive medium to aptly modulate the effective material properties. Here, we propose an active acoustic metamaterial with Willis coupling to drastically extend the tunability of the effective density and bulk modulus with the accessible parameter range enlarged by at least two orders of magnitude compared to that of a non-Willis metamaterial. Traditional active metamaterial designs are based on local resonances without considering the Willis coupling that limit their accessible effective material parameter range. Our design adopts a unit cell structure with two sensor-transducer pairs coupling the acoustic response on both sides of the metamaterial by detecting incident waves and driving active signals asymmetrically superimposed onto the passive response of the material. The Willis coupling results from feedback control circuits with unequal gains. These asymmetric feedback control circuits use Willis coupling to expand the accessible range of the effective density and bulk modulus of the metamaterial. The extreme effective material parameters realizable by the metamaterials will remarkably broaden their applications in biomedical imaging, noise control, and transformation acoustics-based cloaking.

Effects of a health worker-led 3-month yoga intervention on blood pressure of hypertensive patients: a randomised controlled multicentre trial in the primary care setting.

BACKGROUND: Hypertension control remains a major challenge globally. A recent systematic review suggested that yoga has beneficial effects on reducing blood pressure. However, the role of yoga in hypertension management in primary health care has received little attention, and no studies have evaluated the impact of a yoga program fully delivered by health care staff on hypertension. This study, therefore, assessed the effects of a health worker-led yoga intervention on blood pressure reduction among hypertensives patients in the primary care setting. METHODS: This was a multicentric, two-arm, randomised trial conducted among hypertensive patients in seven Ayurveda Health Centres in Nepal between March 2017 and June 2018. One hundred and twenty-one participants who were on or without medications were randomised to intervention (n = 61) and wait-list control (n = 60) groups using stratified block randomisation. Participants in the intervention arm received an intervention consisting of an initial five-day structured yoga training at the centres and then a further home-based practice of yoga for five days a week for the following 90 days. Both intervention and control groups also participated in a 2-h health education session. The primary outcome of this trial was systolic blood pressure at 90-day follow-up. Data were analysed on an intention-to-treat basis using linear mixed-effects regression models. RESULTS: We included all 121 study participants (intervention/control = 61/60) in the primary analysis (52.1% males; mean ± SD age = 47.8 ± 10.8 years). The difference in systolic blood pressure between the intervention group and the control group was - 7.66 mmHg (95% CI: - 10.4, - 4.93). For diastolic blood pressure, the difference was - 3.86 mmHg (95% CI: - 6.65, - 1.06). No adverse events were reported by the participants. CONCLUSIONS: A yoga program for hypertensive patients consisting of a five-day training in health centres and 90 days of practice at home is effective for reducing blood pressure. Significant benefits for hypertensive patients could be expected if such programmes would become a part of the standard treatment practice. TRIAL REGISTRATION: This trial was prospectively registered with the Clinical Trial Registry of India [ CTRI/2017/02/007822 ] on 10/02/2017.

Prevalence and associated factors of hypertension among veterans of the Indian Gorkha regiments living in Pokhara Metropolitan City, Nepal.

BACKGROUND: Hypertension is a major preventable risk factor for cardiovascular disease. Occupational factors such as having served or serving in armed forces may be associated with hypertension. This study aimed to assess the prevalence and factors associated with hypertension among veterans of the Indian Gorkha army living in western Nepal. METHODS: A community-based cross-sectional study was conducted among the veterans living in the Pokhara metropolitan city. Data on blood pressure (BP), anthropometric measurements, and behavioral factors were collected by face-to-face interviews using the World Health Organization's non-communicable disease risk factor surveillance (STEPS) tool. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mm Hg and/or diastolic BP of ≥ 90 mm Hg or currently on antihypertensive medication. RESULTS: The age-adjusted prevalence of hypertension was 66.2 % among the study participants (317). Mean systolic and diastolic blood pressure was 144.5 mmHg (± 18.3) and 89.3mmHg (± 16.0), respectively. Among the hypertensive participants, 67 % were aware of their disease, 90 % of them were under treatment, and 14 % of the individuals who received treatment had their hypertension under control. The proportion of smokers was 12.9 % and alcohol drinker was 86.1 %. One-fourth (25.9 %) of the participants had a family history of hypertension. Veterans aged 55-64 years had higher odds (AOR: 5.3; 95 % CI: 1.8-15.9; p = 0.003) of being associated with hypertension as compared to 35-44 years. Being a current alcohol drinker (AOR: 2.5; 95 % CI: 1.4-4.5; p = 0.003), overweight (AOR: 1.9; 95 % CI: 1.0-3.5; p = 0.04), obese (AOR: 3.1; 95 % CI: 1.1-8.3; p = 0.03) and family history of hypertension (AOR: 2.9; 95 % CI: 1.5-5.8; p = 0.002) were independently associated with hypertension. CONCLUSIONS: Hypertension was prevalent in retired Nepal veterans. Hypertension was associated with a number of modifiable lifestyle and behavioral factors. Our findings suggest the need for screening, education and management of Nepal veterans for hypertension.

Crystal Structures of Wild-Type and F448A Mutant Citrobacter freundii Tyrosine Phenol-Lyase Complexed with a Substrate and Inhibitors: Implications for the Reaction Mechanism.

Tyrosine phenol-lyase (TPL; EC 4.1.99.2) is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the reversible hydrolytic cleavage of l-tyrosine to phenol and ammonium pyruvate. We have shown previously that F448A TPL has kcat and kcat/ Km values for l-tyrosine reduced by ∼104-fold [Phillips, R. S., Vita, A., Spivey, J. B., Rudloff, A. P., Driscoll, M. D., and Hay, S. (2016) ACS Catal. 6, 6770-6779]. We have now obtained crystal structures of F448A TPL and complexes with l-alanine, l-methionine, l-phenylalanine, and 3-F-l-tyrosine at 2.05-2.27 Å and the complex of wild-type TPL with l-phenylalanine at 1.8 Å. The small domain of F448A TPL, where Phe-448 is located, is more disordered in chain A than in wild-type TPL. The complexes of F448A TPL with l-alanine and l-phenylalanine are in an open conformation in both chains, while the complex with l-methionine is a 52:48 open:closed equilibrium mixture in chain A. Wild-type TPL with l-alanine is closed in chain A and open in chain B, and the complex with l-phenylalanine is a 56:44 open:closed mixture in chain A. Thus, the Phe-448 to alanine mutation affects the conformational equilibrium of open and closed active sites. The structure of the 3-F-l-tyrosine quinonoid complex of F448A TPL is unstrained and in an open conformation, with a hydrogen bond from the phenolic OH to Thr-124. These results support our previous conclusion that ground-state strain plays a critical role in the mechanism of TPL.

Leveraging Social Networking Sites for an Autoimmune Hepatitis Genetic Repository: Pilot Study to Evaluate Feasibility.

BACKGROUND: Conventional approaches to participant recruitment are often inadequate in rare disease investigation. Social networking sites such as Facebook may provide a vehicle to circumvent common research limitations and pitfalls. We report our preliminary experience with Facebook-based methodology for participant recruitment and participation into an ongoing study of autoimmune hepatitis (AIH). OBJECTIVE: The goal of our research was to conduct a pilot study to assess whether a Facebook-based methodology is capable of recruiting geographically widespread participants into AIH patient-oriented research and obtaining quality phenotypic data. METHODS: We established a Facebook community, the Autoimmune Hepatitis Research Network (AHRN), in 2014 to provide a secure and reputable distillation of current literature and AIH research opportunities. Quarterly advertisements for our ongoing observational AIH study were posted on the AHRN over 2 years. Interested and self-reported AIH participants were subsequently enrolled after review of study materials and completion of an informed consent by our study coordinator. Participants returned completed study materials, including epidemiologic questionnaires and genetic material, to our facility via mail. Outside medical records were obtained and reviewed by a study physician. RESULTS: We successfully obtained all study materials from 29 participants with self-reported AIH within 2 years from 20 different states. Liver biopsy results were available for 90% (26/29) of participants, of which 81% (21/29) had findings consistent with AIH, 15% (4/29) were suggestive of AIH with features of primary biliary cholangitis (PBC), and 4% (1/29) had PBC alone. A total of 83% (24/29) had at least 2 of 3 proposed criteria: positive autoimmune markers, consistent histologic findings of AIH on liver biopsy, and reported treatment with immunosuppressant medications. Self-reported and physician records were discrepant for immunosuppressant medications or for AIH/PBC diagnoses in 4 patients. CONCLUSIONS: Facebook can be an effective ancillary tool for facilitating patient-oriented research in rare diseases. A social media-based approach transcends established limitations in rare disease research and can further develop research communities.

Impact of a structured yoga program on blood pressure reduction among hypertensive patients: study protocol for a pragmatic randomized multicenter trial in primary health care settings in Nepal.

BACKGROUND: Hypertension control remains a major global challenge. The behavioral approaches recommended for blood pressure reduction are stress reduction, increased exercise and healthy dietary habits. Some study findings suggest that yoga has a beneficial effect in reducing blood pressure. However, the role of yoga on blood pressure has received little attention in existing health care practices in developing countries. This study will be conducted in primary health care facilities in Nepal to assess the effectiveness of a pragmatic yoga intervention to complement standard practice in further reducing blood pressure. METHODS: This will be multicentric, two arms, randomized, nonblinded, pragmatic trial. It will be conducted in seven District Ayurveda Health Centers (DAHCs) in Nepal between July 2017 and June 2018. The study participants will consist of hypertensive patients with or without antihypertensive medication attending to the outpatient department (OPD). One hundred and forty participants will be randomized to treatment or control groups by using a stratified block randomization. At the study site, the treatment arm participants will receive an intervention consisting of five days of structured yoga training and practice of the same package at home with a recommendation of five days a week for the following 90 days. Both the intervention and control groups will receive two hours of health education on lifestyle modifications. The primary outcome of this trial will be the change in systolic blood pressure and it will be assessed after 90 days of the intervention. DISCUSSION: This study will establish the extent to which a yoga intervention package can help reduce blood pressure in hypertensive patients. If proven effective, study findings may be used to recommend the governing bodies and other stakeholders for the integration of yoga in the national healthcare system for the treatment and control of hypertension. TRIAL REGISTRATION: Clinical Trial Registry- India (CTRI); CTRI Reg. No- CTRI/2017/02/007822 . Registered on 10/02/2017.

Design and Implementation of a Novel Web-Based E-Learning Tool for Education of Health Professionals on the Antibiotic Vancomycin.

BACKGROUND: Traditional approaches to health professional education are being challenged by increased clinical demands and decreased available time. Web-based e-learning tools offer a convenient and effective method of delivering education, particularly across multiple health care facilities. The effectiveness of this model for health professional education needs to be explored in context. OBJECTIVES: The study aimed to (1) determine health professionals' experience and knowledge of clinical use of vancomycin, an antibiotic used for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and (2) describe the design and implementation of a Web-based e-learning tool created to improve knowledge in this area. METHODS: We conducted a study on the design and implementation of a video-enhanced, Web-based e-learning tool between April 2014 and January 2016. A Web-based survey was developed to determine prior experience and knowledge of vancomycin use among nurses, doctors, and pharmacists. The Vancomycin Interactive (VI) involved a series of video clips interspersed with question and answer scenarios, where a correct response allowed for progression. Dramatic tension and humor were used as tools to engage users. Health professionals' knowledge of clinical vancomycin use was obtained from website data; qualitative participant feedback was also collected. RESULTS: From the 577 knowledge survey responses, pharmacists (n=70) answered the greatest number of questions correctly (median score 4/5), followed by doctors (n=271; 3/5) and nurses (n=236; 2/5; P<.001). Survey questions on target trough concentration (75.0%, 433/577) and rate of administration (64.9%, 375/577) were answered most correctly, followed by timing of first level (49%, 283/577), maintenance dose (41.9%, 242/577), and loading dose (38.0%, 219/577). Self-reported "very" and "reasonably" experienced health professionals were also more likely to achieve correct responses. The VI was completed by 163 participants during the study period. The rate of correctly answered VI questions on first attempt was 65% for nurses (n=63), 68% for doctors (n=86), and 82% for pharmacists (n=14; P<.001), reflecting a similar pattern to the knowledge survey. Knowledge gaps were identified for loading dose (39.2% correct on first attempt; 64/163), timing of first trough level (50.3%, 82/163), and subsequent trough levels (47.9%, 78/163). Of the 163 participants, we received qualitative user feedback from 51 participants following completion of the VI. Feedback was predominantly positive with themes of "entertaining," "engaging," and "fun" identified; however, there were some technical issues identified relating to accessibility from different operating systems and browsers. CONCLUSIONS: A novel Web-based e-learning tool was successfully developed combining game design principles and humor to improve user engagement. Knowledge gaps were identified that allowed for targeting of future education strategies. The VI provides an innovative model for delivering Web-based education to busy health professionals in different locations.

Improving Resident Physician Participation in Reporting Patient Safety and Quality Concerns.

Background: Reporting medical errors, near misses, and adverse events is an important component of improving patient safety and resident learning. Studies have revealed that event reporting rates can be low for physicians, resident physicians, and fellows. The objective of this quality improvement project was to improve resident reporting of patient safety and quality events and engage residents in the analysis of events at a community-based teaching hospital in the United States. Methods: We developed a program to engage 122 residents from 6 Accreditation Council for Graduate Medical Education-accredited residency programs using a multifaceted approach that included instructing residents how to use the hospital's adverse event reporting system; requiring first-year residents to submit at least 1 report; reviewing all resident reports during a monthly multidisciplinary meeting; and ensuring that each resident who submitted a report received feedback on how the concern was being addressed. Results: The program resulted in a 41.8% (95% CI 31%-53%) absolute increase in the number of residents reporting a concern, and resident submissions led to several documented improvements in patient care. A survey was administered to the residents who submitted reports, and the majority (76.0% response rate) expressed satisfaction with both the reporting system and the feedback about how their submission was being addressed. The responding residents agreed that they were more likely to submit reports because of their experience with the program and that they felt the program would improve safety and the quality of care at the institution. Conclusion: This quality improvement project successfully increased resident event reporting and engaged residents in the review of submitted events. The program can serve as a model for other teaching hospitals.

Using an under-utilised rural hospital to reduce surgical waiting lists.

Objectives This study aimed to evaluate patient outcomes from a 12-month pilot program establishing specialist surgical services in a small rural (Modified Monash Model, MM4) hospital on the south coast of NSW. Methods Suitable patients for ambulatory surgery were selected based on strict anaesthetic, surgical and social criteria. Skills shortfalls among nursing staff, usually with emergency or inpatient experience, were addressed by appropriate re-training and in-service training in scrub, scout and anaesthetic duties. An anonymous post-operative patient survey was administered during the pilot program, which assessed patient experiences and outcomes. Of 162 patients undergoing surgery during the pilot, 50 consecutive participants completed the survey. Results Of the 161 procedures during the pilot program, 100 were performed under sedation and locoregional anaesthesia and 62 under general anaesthesia. Half (n = 86, 53.4%) were complex excisions of malignant skin lesions, and of these 63% also required either a skin graft or local flap repair. Survey respondents reported adequate information and pain relief upon discharge (n = 45, 96%) and 100% were satisfied with the care received. No respondents needed to see a doctor following discharge. There were no mortality events or major issues of morbidity during the study period or subsequently, no further overnight admissions or return to theatre and no re-presentations within 48 h of operating. Two superficial surgical site infections were reported. Conclusions There is merit in drawing on underutilised resources in small rural hospitals in support of initiatives to reduce surgical waitlists. Appropriate outpatient surgeries can be safely performed with high levels of patient satisfaction.

Assessment of Registered Clinical Trial Designs: Comparison of L-Arginine and/or L-Citrulline Interventions for Hypertension.

BACKGROUND: L-Arginine (Arg) is an essential amino acid and a precursor for the synthesis of vascular nitric oxide, while L-Citrulline is a non-essential amino acid substrate for increasing L-arginine. Both L-arginine and L-Citrulline in translational studies may acutely lower the blood pressure. Current meta-analysis for L-arginine or L-Citrulline interventions in blood pressure have identified significant heterogeneity. Clinical trial evidence for L-arginine or L-Citrulline in chronic blood pressure reduction in the general population requires an examination of trial designs, as not all translational studies may have influenced vascular reactivity. Our aims are to explore whether L-arginine and L-citrulline intervention trials in chronic blood pressure consider standardized end points relevant to the general adult populations. METHODS: A step-wise search on clinicaltrials.gov, the U.S. Library of Medicine registry for clinical trials, was performed including the following keyword search parameters: "completed" "L-Citrulline" "L-arginine" trial", and "adults", involving "blood pressure" reduction as a primary end point in adult humans. RESULTS: Of the forty-four completed trials, only five were included for analysis. Following the careful evaluation of trial design, we observed heterogeneity across participant inclusion criteria (population sample size, age range, sex), interventional design (dosages, duration), and primary outcomes, measured with respect to changes in diastolic or systolic blood pressure. CONCLUSION: In conclusion, there is a lack of robust trial design evidence to suggest that L-arginine or L-Citrulline, based on current RCTs in the general population, have an overall positive effect on vascular endothelial reactivity and a beneficial chronic blood pressure-lowering effect. Indeed, conclusions drawn from human meta-analysis studies have been heterogenous between studies, which may be attributed to study design heterogeneity, including differences in sample population, age, and blood pressure at the time of entry. Inconsistencies in the study design poses a challenge for systematic reviews and meta-analysis to accurately assess the effect size and impact of L-arginine or L-citrulline on both systolic and diastolic blood pressure.

Discovery of genomic loci for liver health and steatosis reveals overlap with glutathione redox genetics.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States, encompassing a wide spectrum of liver pathologies including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite its high prevalence, there are no medications currently approved by the Food and Drug Administration for the treatment of NAFLD. Recent work has suggested that NAFLD has a strong genetic component and identifying causative genes will improve our understanding of the molecular mechanisms contributing to NAFLD and yield targets for future therapeutic investigations. Oxidative stress is known to play an important role in NAFLD pathogenesis, yet the underlying mechanisms accounting for disturbances in redox status are not entirely understood. To better understand the relationship between the glutathione redox system and signs of NAFLD in a genetically-diverse population, we measured liver weight, serum biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and graded liver pathology in a large cohort of Diversity Outbred mice. We compared hepatic endpoints to those of the glutathione redox system previously measured in the livers and kidneys of the same mice, and we screened for statistical and genetic associations using the R/qtl2 software. We discovered several novel genetic loci associated with markers of liver health, including loci that were associated with both liver steatosis and glutathione redox status. Candidate genes within each locus point to possible new mechanisms underlying the complex relationship between NAFLD and the glutathione redox system, which could have translational implications for future studies targeting NAFLD pathology.

Global google trends for construction demonstrate low search volume index for stress, mental and suicide.

The comparison of Google internet searches for English words in construction for "construction stress", "construction mental" and "construction suicide" with reference to "construction worker" has not previously been undertaken. It is important to understand internet interest across these 3 terms as all are relevant to mental health and stress in construction. Suicide risk is significantly complex and multifactorial. Our aim is to investigate internet search interest across construction with a focus on mental, stress and suicide, and determine whether there is consistent interest across these search terms. METHODS: Using Google Trends, data on global search queries we compared "construction mental" or "construction stress" and "construction suicide". Two time periods were compared, the last 5 years and the last 24 months, both till December 8th, 2022. The relationship between web search interest, reflected by search volume index (SVI) for society and community versus the business and industrial category and health category were evaluated. RESULTS: Open category searches on Google trends for the key words "construction mental" or "construction stress" demonstrated moderate SVI peaks over a 5-year period. Sub-group analyses for the industrial and business category demonstrated consistent low interest in suicide compared to search terms related to stress or mental health. CONCLUSION: There is limited online interest in construction mental and stress and even less interest in suicide.

Change in Methicillin-Resistant Staphylococcus aureus Testing in the Intensive Care Unit as an Antimicrobial Stewardship Initiative.

Background: Methicillin-resistant Staphylococcus aureus (MRSA)-associated infections are a cause of morbidity and mortality in the intensive care unit (ICU). Vancomycin is a treatment option but is not without risks. Methods: A MRSA testing change-the switch from culture to polymerase chain reaction-was implemented at 2 adult (tertiary and community) ICUs located in a Midwestern US health system. Data from 2016 to 2020 were included in the study, and the median change in time to test results was examined. Results: During the study period, 71% of 19,975 patients seen at the 2 ICUs received MRSA testing. In the preintervention period, 91% and 99% of patients at the tertiary and community hospitals received testing via culture, respectively. Culture testing was used 1% and ∼0% of the time at the tertiary and community hospitals, respectively, in the postintervention period. A counterfactual estimate showed 36 (95% credible interval [CrI], 35, 37) and 32 (95% CrI, 31, 33) fewer hours until results were available at the tertiary and community hospitals, respectively. Conclusion: After the testing change, MRSA results were available in less time. Obtaining results sooner can assist with antimicrobial stewardship through the potential delay in initiating therapies such as vancomycin and/or quicker de-escalation of such therapies.

A clinically useful and biologically informative genomic classifier for papillary thyroid cancer.

Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm (HighLifeR) to 502 cases annotated by The Cancer Genome Atlas Project to derive an accurate molecular prognostic classifier. Unsupervised analysis of the 82 genes that were most closely associated with recurrence after surgery enabled the identification of three unique molecular subtypes. One subtype had a high recurrence rate, an immunosuppressed microenvironment, and enrichment of the EZH2-HOTAIR pathway. Two other unique molecular subtypes with a lower rate of recurrence were identified, including one subtype with a paucity of BRAFV600E mutations and a high rate of RAS mutations. The genomic risk classifier, in addition to tumor size and lymph node status, enabled effective prognostication that outperformed the American Thyroid Association clinical risk stratification. The genomic classifier we derived can potentially be applied preoperatively to direct clinical decision-making. Distinct biological features of molecular subtypes also have implications regarding sensitivity to radioactive iodine, EZH2 inhibitors, and immune checkpoint inhibitors.

Analysis and comparison of web searches in Google Trends in the business and industrial category for the word's "resilience" and "wellbeing" during COVID-19.

OBJECTIVE: The comparison of Google internet searches for worker wellbeing and resilience during COVID has not previously been undertaken. It is important to understand interest in wellbeing and resilience as both constructs influence health and burnout. Our objective to investigate internet interest in both wellbeing and resilience during COVID. Using Google Trends, data on global search English word queries we compared "worker wellbeing" or "wellbeing" versus "resilience" or "psychological resilience". Two time periods were compared, the last 5 years and the last 12 months, both up until the end of April 2022. The relationship between web search interest, reflected by search volume index (SVI) for all categories versus the business and industrial category evaluated. RESULTS: Open category searches on Google trends for the key words "worker wellbeing" or "wellbeing" demonstrated increased SVI peaks for COVID periods. Sub-group analyses demonstrated the category business and industrial had less web search interest in wellbeing and an increase in search terms related to resilience but not psychological resilience. Online interest in wellbeing and resilience represents a complex search metric. There are differing search interests depending on whether the category business and industrial is chosen versus the general Google Trends category.

Characteristics and retention of emergency department patients who left without being seen (LWBS).

A retrospective observational study was conducted for patients 18 years or older presenting to a Midwestern emergency department (ED) in the United States during February 2019-January 2020 to characterize associated subsequent care utilization in patients who left the ED without being seen. Patients were classified as left without being seen (LWBS) based on documented ED disposition. The healthcare system's records were reviewed for any associated utilizations within 3 weeks following the initial ED encounter. During the study period, 45,456 patients presented to the ED, with 2269 (5.0%) classified as LWBS. The median documented time until patients left the ED was 112 min. Of these patients, 1257 (55.4%) had a subsequent encounter within the health system within 3 weeks and 920 (73.2%) of these visits were determined to be related to the LWBS chief complaint. These visits included 67.5% of patients returning to ED or hospital, 27.5% to primary care or an urgent care clinic, and 5.0% to a specialty or other provider appointment. Of patients returning to ED, 78.1% did so within 72 h. Patients without a subsequent health system associated encounter tended to be younger, female, non-White, and present with possible lower-acuity chief complaints. At least one-half of LWBS patients sought care related to the concerns by a health system provider within 3 weeks of the initial encounter within the same system. The high prevalence of ED returns within a narrow turnaround window highlights a missed opportunity to provide services to these patients during their initial encounter.

Quantitative trait mapping in Diversity Outbred mice identifies novel genomic regions associated with the hepatic glutathione redox system.

The tripeptide glutathione (GSH) is instrumental to antioxidant protection and xenobiotic metabolism, and the ratio of its reduced and oxidized forms (GSH/GSSG) indicates the cellular redox environment and maintains key aspects of cellular signaling. Disruptions in GSH levels and GSH/GSSG have long been tied to various chronic diseases, and many studies have examined whether variant alleles in genes responsible for GSH synthesis and metabolism are associated with increased disease risk. However, past studies have been limited to established, canonical GSH genes, though emerging evidence suggests that novel loci and genes influence the GSH redox system in specific tissues. The present study marks the most comprehensive effort to date to directly identify genetic loci associated with the GSH redox system. We employed the Diversity Outbred (DO) mouse population, a model of human genetics, and measured GSH and the essential redox cofactor NADPH in liver, the organ with the highest levels of GSH in the body. Under normal physiological conditions, we observed substantial variation in hepatic GSH and NADPH levels and their redox balances, and discovered a novel, significant quantitative trait locus (QTL) on murine chromosome 16 underlying GSH/GSSG; bioinformatics analyses revealed Socs1 to be the most likely candidate gene. We also discovered novel QTL associated with hepatic NADP+ levels and NADP+/NADPH, as well as unique candidate genes behind each trait. Overall, these findings transform our understanding of the GSH redox system, revealing genetic loci that govern it and proposing new candidate genes to investigate in future mechanistic endeavors.

Genetic mapping of renal glutathione suggests a novel regulatory locus on the murine X chromosome and overlap with hepatic glutathione regulation.

Glutathione (GSH) is a critical cellular antioxidant that protects against byproducts of aerobic metabolism and other reactive electrophiles to prevent oxidative stress and cell death. Proper maintenance of its reduced form, GSH, in excess of its oxidized form, GSSG, prevents oxidative stress in the kidney and protects against the development of chronic kidney disease. Evidence has indicated that renal concentrations of GSH and GSSG, as well as their ratio GSH/GSSG, are moderately heritable, and past research has identified polymorphisms and candidate genes associated with these phenotypes in mice. Yet those discoveries were made with in silico mapping methods that are prone to false positives and power limitations, so the true loci and candidate genes that control renal glutathione remain unknown. The present study utilized high-resolution gene mapping with the Diversity Outbred mouse stock to identify causal loci underlying variation in renal GSH levels and redox status. Mapping output identified a suggestive locus associated with renal GSH on murine chromosome X at 51.602 Mbp, and bioinformatic analyses identified apoptosis-inducing factor mitochondria-associated 1 (Aifm1) as the most plausible candidate. Then, mapping outputs were compiled and compared against the genetic architecture of the hepatic GSH system, and we discovered a locus on murine chromosome 14 that overlaps between hepatic GSH concentrations and renal GSH redox potential. Overall, the results support our previously proposed model that the GSH redox system is regulated by both global and tissue-specific loci, vastly improving our understanding of GSH and its regulation and proposing new candidate genes for future mechanistic studies.

Increasing use of intraoperative cholangiogram in Australia: is it evidence-based?

BACKGROUND: The role of routine intraoperative cholangiograms (IOCs) for prevention of bile duct injury (BDI) is contentious. There are recent reports of limited utility of IOC in preventing BDI. In Australia, IOCs are used more frequently than internationally. This study aimed to evaluate the rate of IOC use in Australia and explore potential changes in practice in light of evolving evidence for the utility of IOC. METHODS: Data were collated using service item numbers in Medicare Benefits Scheme records on the Australian Government Medicare website, for services claimed between 1 January 2001 and 31 December 2019. These data were used to analyse trends in rates of IOC, cholecystectomy and BDI repair. Data were age-standardized to account for changes in the population over time. RESULTS: The number of IOCs claimed increased by 31.8% and cholecystectomies by 7.0% over the study period. Age-standardized service rates per 100 000 persons increased by 5.5 and 32.6, respectively. Rates of IOC per 100 000 cholecystectomies steadily increased across the study period, while BDI repair rates remained low and erratic. CONCLUSION: Increasing use of IOC over the last 20 years reflects a trend towards routine rather than selective IOC; however, there is little discernible change in the number of BDIs requiring repair procedures. This suggests that routine IOC use to prevent or minimize BDI is unwarranted. Further investigation is required into the selective IOC use in high-risk patients rather than mandatory use in all patients.