A systematic review on the biochemical threshold of mitochondrial genetic variants.

Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, P = 0.01, n = 13); however, no correlation was observed in fibroblasts (P = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.

Dynamic analysis of geomaterials using microwave sensing.

Precise characterization of geomaterials improves subsurface energy extraction and storage. Understanding geomaterial property, and the complexities between petrophysics and geomechanics, plays a key role in maintaining energy security and the transition to a net zero global carbon economy. Multiple sectors demand accurate and rapid characterization of geomaterial conditions, requiring the extraction of core plugs in the field for full-field characterization and analysis in the laboratory. We present a novel technique for the non-invasive characterization of geomaterials by using Frequency Modulated Continuous Wave (FMCW) radar in the K-band, representing a new application of microwave radar. We collect data through the delivery of FMCW wave interactions with geomaterials under static and dynamic conditions and show that FMCW can detect fluid presence, differentiate fluid type, indicate the presence of metallic inclusions and detect imminent failure in loaded sandstones by up to 15 s, allowing for greater control in loading up to a failure event. Such precursors have the potential to significantly enhance our understanding of, and ability to model, geomaterial dynamics. This low-cost sensing method is easily deployable, provides quicker and more accessible data than many state-of-the-art systems, and new insights into geomaterial behavior under dynamic conditions.

Catheter-associated meatal pressure injuries (CAMPI) in patients with long-term urethral catheters-a cross-sectional study of 200 patients.

Background: Indwelling urethral catheters (IDC) are ubiquitous to healthcare settings, and are associated with many familiar risks like haematuria, infections, bladder spasms and stones. However, a less known complication is catheter-associated meatal pressure injury (CAMPI), especially in those with long-term IDCs. The objective of this study was to explore the prevalence, associated features and management of CAMPI in adults with a long-term IDC. Methods: A cross-sectional multi-centre study was undertaken of 200 adults with a long-term IDC across regional south-west Queensland, Australia between June 2019 to June 2021. The prevalence of CAMPI was determined by clinical examination, voluntary surveys completed by participants and documentation in medical records. Key IDC statistics included total duration of IDC, location of IDC changes, IDC size, type and fixation. Results: Out of 200 adults with a long-term IDC, 9% (18/200) had a CAMPI. There was a higher prevalence of male CAMPI (17/169, 10%) compared to female CAMPI (1/31, 3%). The median time to identification of a CAMPI after initial IDC insertion was 12 weeks (2-136 weeks), but occurred as soon as 2 weeks. CAMPI formation was associated with IDC changes in the community, impaired mobility and congestive cardiac failure (CCF). CAMPI were mostly treated by conservative means given the frailty of the population. Conclusions: Poor mobility, community-managed IDCs, and CCF were all found to have statistically significant associations with the development of CAMPI. CAMPI represents an important and underserved iatrogenic complication within urology practice, and greater awareness is needed to prevent it in vulnerable patients with long-term IDCs.

Anomaly Detection Methods in Autonomous Robotic Missions.

Since 2015, there has been an increase in articles on anomaly detection in robotic systems, reflecting its growing importance in improving the robustness and reliability of the increasingly utilized autonomous robots. This review paper investigates the literature on the detection of anomalies in Autonomous Robotic Missions (ARMs). It reveals different perspectives on anomaly and juxtaposition to fault detection. To reach a consensus, we infer a unified understanding of anomalies that encapsulate their various characteristics observed in ARMs and propose a classification of anomalies in terms of spatial, temporal, and spatiotemporal elements based on their fundamental features. Further, the paper discusses the implications of the proposed unified understanding and classification in ARMs and provides future directions. We envisage a study surrounding the specific use of the term anomaly, and methods for their detection could contribute to and accelerate the research and development of a universal anomaly detection system for ARMs.

National Institutes of Health Funding for Tuberculosis Comorbidities Is Disproportionate to Their Epidemiologic Impact.

Tuberculosis (TB) is a leading infectious killer worldwide. We systematically searched the National Institutes of Health Research, Portfolio Online Reporting Tools Expenditures and Results (RePORTER) website to compare research funding for key TB comorbidities-undernutrition, alcohol use, human immunodeficiency virus, tobacco use, and diabetes-and found a large mismatch between the population attributable fraction of these risk factors and the funding allocated to them.

Translation in action: Influence, collaboration, and evolution of COVID-19 research with Clinical and Translational Science Awards consortium support.

The National Institutes of Health (NIH)'s Clinical and Translational Science Awards (CTSA) consortium aims to accelerate translational processes that move discoveries from bench to bedside. The coronavirus disease 2019 (COVID-19) pandemic presented unmatched challenges and applications for CTSA hubs nationwide. Our study used bibliometrics to assess features of COVID-19 publications supported by the national CTSA program to characterize the consortium's response to the pandemic. Our goal was to understand relative scientific influence, collaboration across hubs, and trends in research emphasis over time. We identified publications from NIH's curated iSearch COVID-19 Publication Portfolio from February 2020 to February 2023; 3234 peer-reviewed articles relevant to COVID-19 cited a CTSA grant. All 66 CTSA hubs were represented, with large-size and longstanding hubs contributing more publications. Most publications cited UL1 grants, 457 cited KL2/TL1 training grants, and 164 cited multiple hub grants. Compared to a random sample of non-CTSA-supported COVID-19 publications, the CTSA portfolio exhibited greater clinical relevance, more human research, and higher altmetric and citation influence. Results were similar for multi-hub publications involving networked initiatives like multi-site clinical trials or the National COVID-19 Cohort Collaborative. Shifts from molecular/cellular-oriented research toward human-oriented research over time were evident, demonstrating translation in action. Results illuminate how the CTSA consortium confronted the pandemic through high-quality projects oriented toward human research, working across hubs on high-value collaborations, advancing along the translational spectrum over time. Findings validate CTSA hubs as critical support structures during health emergencies.

Comparing preoperative fasting and ultrasound-measured intravascular volume status in elective surgery, enhanced recovery patients versus inpatient, urgent surgery patients and the ability of IVC collapsibility to predict post-induction hypotension.

Hypotension following induction of general anaesthesia has been shown to result in increased complications and mortality postoperatively. Patients admitted to the hospital undergoing urgent surgery are often fasted from fluids for significant periods compared to elective patients subject to Enhanced Recovery After Surgery protocols despite guidelines stating that a two-hour fast is sufficient. The aim of this prospective, observational study was to compare fasting times and intravascular volume status between elective surgery patients subject to enhanced recovery protocols and inpatient, urgent surgery patients and to assess differences in the incidence of post-induction hypotension. Fasting data was obtained by questionnaire in the preoperative area in addition to inferior vena cava collapsibility index, a non-invasive measure of intravascular volume. Blood pressure readings and drug administration for the ten minutes following induction were obtained from patients' charts. Inpatients undergoing urgent surgery were fasted significantly longer than enhanced recovery patients and had lower intravascular volume. However, no difference was found in the incidence of post-induction hypotension.

Venous Excess Ultrasound (VExUS Grading to Assess Perioperative Fluid Status for Noncardiac Surgeries: a Prospective Observational Pilot Study.

Objectives: Perioperative fluid administration impacts the rate of complications following surgery. VExUS grading system is a standardized point of care ultrasound (POCUS)-based, comprehensive method to assess volume status. VExUS could serve as a tool to guide fluid management, if validated perioperatively. The primary aim was to assess the success rate of obtaining required windows for VExUS grading , as well as the feasibility within a perioperative setting among noncardiac surgery. Further, this study describes the incidence of perioperative venous congestion and associations with 30-day postoperative complications. Methods: This observational study was conducted in non-critically ill adults undergoing noncardiac surgery. Patients were scanned preoperatively, in the post anesthesia care unit (PACU), and 24 hours postoperatively for venous congestion. Researchers retrospectively captured 30-day complications for multivariate analyses. Results: The cohort included 69 participants. Ninety-one percent of scans over all timepoints were successfully completed. Pre-operatively, 57 (83%) scans were Grade 0, and 11 (16%) were Grade 1. Venous congestion was observed in 29 (44%) patients in the PACU (n=66). 22 (33%) patients were Grade 1, while 7 (11%) were Grade 2. At 24 hours (n=63), 31 patients (49%) had venous congestion: 20 (32%) Grade 1 and 11 (17%) Grade 2. Of the pre-operative Grade 0, 28 (50%) had at least one postoperative scan with venous congestion. No patients were Grade 3 at any timepoint. The 30-day complication rate was 32% (n=22). Eleven (16%) patients developed acute kidney injury (AKI). There was no statistically significant association between VExUS grading and all-cause complications or AKI. Conclusion: This study demonstrates that perioperative VExUS scoring is a feasible tool among a variety of noncardiac surgeries. We highlight that venous congestion is common and increases postoperatively within non-ICU populations. Larger studies are needed to assess the relationship between VExUS grading and postoperative complications.

Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review.

OBJECTIVES: As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation. DESIGN: Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa. DATA SOURCES: PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences. ELIGIBILITY CRITERIA: Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure. DATA EXTRACTION AND SYNTHESIS: We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature. RESULTS: Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret. CONCLUSIONS: The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%-50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure. PROSPERO REGISTRATION NUMBER: CRD42022324136.

The effect of postpartum lifestyle interventions on blood pressure: a systematic literature review.

Postpartum lifestyle modification is recommended to hypertension risk. We conducted a systematic literature review to assess the evidence for postpartum lifestyle interventions to reduce blood pressure. We searched for relevant publications from 2010 through November 2022. Two authors independently conducted article screening and data extraction; a third resolved discrepancies. Ultimately, nine studies met inclusion criteria. Most were randomized controlled trials and had sample sizes <100. In all but one of the eight studies reporting race data, nearly all participants identified as White. None of the studies reported a significant intervention effect on blood pressure. However, most interventions were associated with improvements in other outcomes, such as physical activity. Overall, the evidence for postpartum lifestyle interventions to reduce blood pressure is limited to a handful of studies characterized by small sample sizes and a lack of racial diversity. Additional research with larger samples, more diverse populations, and intermediate outcomes is warranted.

Perioperative Blood Transfusions and Anastomotic Leak After Colorectal Surgery for Cancer in an Australian Hospital.

PURPOSE: Peri-operative blood transfusion has been identified as a risk factor for anastomotic leak in recent studies, but little is known about which patients are at risk for blood transfusion. This study aims to assess the relationship between blood transfusion and anastomotic leak and factors predisposing to leak in patients undergoing colorectal cancer surgery. METHODS: This retrospective cohort study was conducted in a tertiary hospital in Brisbane, Australia, between 2010 and 2019. A total of 522 patients underwent resection of colorectal cancer with primary anastomosis with no covering stoma and the prevalence of anastomotic leak was compared between those who had had perioperative blood transfusion(s) and those who had not. RESULTS: A total of 19 of 522 patients undergoing surgery for colorectal cancer had developed an anastomotic leak (3.64%). 11.3% of patients who had had a perioperative blood transfusion developed an anastomotic leak whereas 2.2% of patients who had not had a blood transfusion developed an anastomotic leak (p = 0.0002). Patients undergoing procedure on their right colon had proportionally more blood transfusions and this approached statistical significance (p = 0.06). Patients who received a greater quantity of units of blood transfusion prior to their diagnosis of anastomotic leak were more likely to develop an anastomotic leak (p = 0.001). CONCLUSION: Perioperative blood transfusions are associated with a significantly increased risk of an anastomotic leak following bowel resection with primary anastomosis for colorectal cancer.

A scoping review of how early-stage knee osteoarthritis has been defined.

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. METHODS: We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. RESULTS: Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren-Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. CONCLUSION: Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

FedBranched: Leveraging Federated Learning for Anomaly-Aware Load Forecasting in Energy Networks.

Increased demand for fast edge computation and privacy concerns have shifted researchers' focus towards a type of distributed learning known as federated learning (FL). Recently, much research has been carried out on FL; however, a major challenge is the need to tackle the high diversity in different clients. Our research shows that using highly diverse data sets in FL can lead to low accuracy of some local models, which can be categorised as anomalous behaviour. In this paper, we present FedBranched, a clustering-based framework that uses probabilistic methods to create branches of clients and assigns their respective global models. Branching is performed using hidden Markov model clustering (HMM), and a round of branching depends on the diversity of the data. Clustering is performed on Euclidean distances of mean absolute percentage errors (MAPE) obtained from each client at the end of pre-defined communication rounds. The proposed framework was implemented on substation-level energy data with nine clients for short-term load forecasting using an artificial neural network (ANN). FedBranched took two clustering rounds and resulted in two different branches having individual global models. The results show a substantial increase in the average MAPE of all clients; the biggest improvement of 11.36% was observed in one client.

Perioperative Management of Vitamin K Antagonists and Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. RESEARCH QUESTION: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures? STUDY DESIGN AND METHODS: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate. RESULTS: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE. INTERPRETATION: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.

Evaluation of machine learning models as decision aids for anesthesiologists.

Machine Learning (ML) models have been developed to predict perioperative clinical parameters. The objective of this study was to determine if ML models can serve as decision aids to improve anesthesiologists' prediction of peak intraoperative glucose values and postoperative opioid requirements. A web-based tool was used to present actual surgical case and patient information to 10 practicing anesthesiologists. They were asked to predict peak glucose levels and post-operative opioid requirements for 100 surgical patients with and without presenting ML model estimations of peak glucose and opioid requirements. The accuracies of the anesthesiologists' estimates with and without ML estimates as reference were compared. A questionnaire was also sent to the participating anesthesiologists to obtain their feedback on ML decision support. The accuracy of peak glucose level estimates by the anesthesiologists increased from 79.0 ± 13.7% without ML assistance to 84.7 ± 11.5% (< 0.001) when ML estimates were provided as reference. The accuracy of opioid requirement estimates increased from 18% without ML assistance to 42% (p < 0.001) when ML estimates were provided as reference. When ML estimates were provided, predictions of peak glucose improved for 8 out of the 10 anesthesiologists, while predictions of opioid requirements improved for 7 of the 10 anesthesiologists. Feedback questionnaire responses revealed that the anesthesiologist primarily used the ML estimates as reference to modify their clinical judgement. ML models can improve anesthesiologists' estimation of clinical parameters. ML predictions primarily served as reference information that modified an anesthesiologist's clinical estimate.

Quality of Recovery After Rotator Cuff Repair With Interscalene Liposomal Bupivacaine Versus Interscalene Nerve Catheter.

Background: Interscalene nerve catheters have been proven to be effective in managing pain after rotator cuff repair (RCR) surgery. Liposomal bupivacaine is a newer approved therapy for use around the interscalene brachial plexus, but its analgesic efficacy has limited supporting data in various patient populations. Purpose/Hypothesis: The purpose of this study was to investigate the quality of recovery after arthroscopic RCR in patients who received either single-injection interscalene liposomal bupivacaine or an interscalene peripheral nerve catheter. It was hypothesized that interscalene peripheral nerve catheters would provide more reliable analgesia and improved patient satisfaction 48 hours after surgery. Study Design: Cohort study; Level of evidence, 2. Methods: Enrolled were 93 consecutive patients who underwent arthroscopic rotator cuff surgery at a single ambulatory surgery center between October 2020 and June 2021. Of these patients, 13 were lost to follow-up; thus, 80 patients were included in statistical analysis. One group of patients (n = 48) received a preoperative interscalene nerve block placed with 10 mL 0.5% bupivacaine and 10 mL 1.3% liposomal bupivacaine. The second group (n = 32) received a preoperative interscalene catheter with an initial bolus of 20 mL 0.25% bupivacaine and a 0.2% ropivacaine infusion by an elastomeric pump set at 10 mL/hr for 48 hours. The primary outcome was the difference between preoperative and 48-hour postoperative quality of recovery-15 (QoR-15) scores. Secondary outcomes included visual analog pain scores, opioid use, and patient satisfaction. Complications and adverse effects were also noted. The Kruskal-Wallis test was used to analyze means and standard deviations for continuous endpoints; Fisher exact test was used to analyze counts and proportions for categorical endpoints. Results: The liposomal bupivacaine group had a mean reduction of 3.9 in their postoperative QoR-15 scores, and the catheter group had a mean reduction of 25.1 in their postoperative QoR-15 scores, indicating a significantly worse functional recovery period compared with liposomal bupivacaine within the first 48 hours (P < .001). Patients who received liposomal bupivacaine also had significantly lower pain scores on the second postoperative day, improved quality of sleep, and improved satisfaction with analgesia (P < .05 for all). Conclusion: The use of interscalene liposomal bupivacaine demonstrated significantly improved quality of recovery when compared with interscalene nerve catheter after RCR.

Perioperative Management of Antiplatelet Therapy: A Systematic Review and Meta-analysis.

Objective: To summarize the available evidence about the perioperative management of patients who are receiving long-term antiplatelet therapy and require elective surgery/procedures. Methods: This systematic review supports the development of the American College of Chest Physicians guideline on the perioperative management of antiplatelet therapy. A literature search of MEDLINE, EMBASE, Scopus and Cochrane databases was conducted from each database's inception to July 16, 2020. Meta-analyses were conducted when possible. Results: In patients receiving long-term antiplatelet therapy and undergoing elective noncardiac surgery, the available evidence did not show a significant difference in major bleeding between a shorter vs longer antiplatelet interruption, with low certainty of evidence (COE). Compared with patients who received placebo perioperatively, aspirin continuation was associated with increased risk of major bleeding (relative risk [RR], 1.31; 95% CI, 1.15-1.50; high COE) and lower risk of major thromboembolism (RR, 0.74; 95% CI, 0.58-0.94; moderate COE). During antiplatelet interruption, bridging with low-molecular-weight heparin was associated with increased risk of major bleeding compared with no bridging (RR, 1.86; 95% CI, 1.24-2.79; very low COE). Continuation of antiplatelets during minor dental and ophthalmologic procedures was not associated with a statistically significant difference in the risk of major bleeding (very low COE). Conclusion: This systematic review summarizes the current evidence about the perioperative management of antiplatelet therapy and highlights the urgent need for further research, particularly with the increasing prevalence of patients taking 1 or more antiplatelet agents.

Electrocardiographic Interference on Bispectral Index Monitor: A Case of Crossed Wires.

The Bispectral Index (BIS) has been widely utilized to monitor patients' levels of consciousness during anesthesia. Despite its practicality and prevalence, BIS monitors have been reported to show erroneous readings due to various factors that interfere with the proper reading of the brain's electrical activity. We present a case where the BIS monitor misinterpreted the patient's cardiac activity as her neural activity and resulted in a falsely elevated BIS number despite proper placement and lack of underlying patient medical condition, including neurological injury. It is crucial to remain vigilant about monitoring and understanding BIS readings to assess patients' awareness and effectiveness of anesthesia properly.