Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme, PRPS2, to drive cancer.

Cancer cells must integrate multiple biosynthetic demands to drive indefinite proliferation. How these key cellular processes, such as metabolism and protein synthesis, crosstalk to fuel cancer cell growth is unknown. Here, we uncover the mechanism by which the Myc oncogene coordinates the production of the two most abundant classes of cellular macromolecules, proteins, and nucleic acids in cancer cells. We find that a single rate-limiting enzyme, phosphoribosyl-pyrophosphate synthetase 2 (PRPS2), promotes increased nucleotide biosynthesis in Myc-transformed cells. Remarkably, Prps2 couples protein and nucleotide biosynthesis through a specialized cis-regulatory element within the Prps2 5' UTR, which is controlled by the oncogene and translation initiation factor eIF4E downstream Myc activation. We demonstrate with a Prps2 knockout mouse that the nexus between protein and nucleotide biosynthesis controlled by PRPS2 is crucial for Myc-driven tumorigenesis. Together, these studies identify a translationally anchored anabolic circuit critical for cancer cell survival and an unexpected vulnerability for "undruggable" oncogenes, such as Myc. PAPERFLICK:

Lightning Pose: improved animal pose estimation via semi-supervised learning, Bayesian ensembling and cloud-native open-source tools.

Contemporary pose estimation methods enable precise measurements of behavior via supervised deep learning with hand-labeled video frames. Although effective in many cases, the supervised approach requires extensive labeling and often produces outputs that are unreliable for downstream analyses. Here, we introduce 'Lightning Pose', an efficient pose estimation package with three algorithmic contributions. First, in addition to training on a few labeled video frames, we use many unlabeled videos and penalize the network whenever its predictions violate motion continuity, multiple-view geometry and posture plausibility (semi-supervised learning). Second, we introduce a network architecture that resolves occlusions by predicting pose on any given frame using surrounding unlabeled frames. Third, we refine the pose predictions post hoc by combining ensembling and Kalman smoothing. Together, these components render pose trajectories more accurate and scientifically usable. We released a cloud application that allows users to label data, train networks and process new videos directly from the browser.

Real-time millimeter wave holography with an arrayed detector.

Millimeter and terahertz wave imaging has emerged as a powerful tool for applications such as security screening, biomedical imaging, and material analysis. However, intensity images alone are often insufficient for detecting variations in the dielectric constant of a sample, and extraction of material properties without additional phase information requires extensive prior knowledge of the sample. Digital holography provides a means for intensity-only detectors to reconstruct both amplitude and phase images. Here we utilize a commercially available source and detector array, both operating at room temperature, to perform digital holography in real-time for the first time in the mm-wave band (at 290 GHz). We compare the off-axis and phase-shifting approaches to digital holography and discuss their trade-offs and practical challenges in this regime. Owing to the low pixel count, we find phase-shifting holography to be the most practical and high fidelity approach for such commercial mm-wave cameras even under real-time operational requirements.

Investigating Alexithymia as a Moderator of Outcomes in a Randomized Controlled Trial of an Online Intervention for Co-Occurring Depression and Hazardous Alcohol Use: Enquête sur l'alexithymie en tant que modérateur des résultats dans un essai randomisé contrôlé d'une intervention en ligne pour la dépression concomitante et la consommation dangereuse d'alcool.

OBJECTIVE: Alexithymia is characterized by difficulty identifying and/or describing emotions, reduced imaginal processes, and externally oriented thinking. High levels of alexithymia may increase the challenge of supporting individuals with co-occurring depression and hazardous alcohol use. This secondary analysis sought to investigate whether or not alexithymia moderated the outcomes of an online intervention for depression and alcohol use. METHOD: As part of a randomized controlled trial, 988 participants were randomly assigned to receive an intervention dually focused on depression and alcohol use, or an intervention only focused on depression. The pre-specified mediation hypothesis was that changes in drinking at 3 months follow-up would effect the association between the intervention and change in depression at 6 months. This secondary analysis extends the investigation by adding alexithymia as a moderator. RESULTS: The current analysis demonstrated that including alexithymia as a moderator resulted in a conditional direct effect. Specifically, there was an intervention effect where participants who received the combined depression and alcohol intervention had larger improvements in their depression scores at 6 months, but this was only when their alexithymia score at baseline was also high (60.5 or higher). CONCLUSION: These results suggest that treatment planning and intervention effectiveness could be informed and optimized by taking alexithymia severity into consideration. This is especially merited as alexithymia can contribute to the weaker therapeutic alliance, more distress and dysphoria, shorter periods of abstinence, and more severe depression, compounding the complexity of supporting individuals with comorbid conditions. More research is needed to systematically investigate these possible modifying effects. PLAIN LANGUAGE TITLE: Does difficulty identifying/describing emotions or externally-oriented thinking influence the effectiveness of an intervention among people with both depression and hazardous alcohol use?

In a recent study we recruited participants who were concerned with both their alcohol use and low mood. We provided two different online interventions. Half of the participants received an intervention designed for both concerns and half received an intervention that addressed only depression. We hypothesized that receiving the combined intervention for both concerns would result in greater benefits, however, our results indicated no apparent difference. This analysis uses the same data, but investigated the influences of alexithymia on the effectiveness of the interventions. Alexithymia is defined as having difficulty identifying/describing emotions and/or thinking more about external events than internal feelings. It commonly co-occurs with depression and with hazardous alcohol use and can increase the challenge of supporting individuals with these co-occurring concerns. The results of this analysis showed support for our original hypothesis that participants who received the intervention that addressed both their mood and alcohol concerns had lower depression scores 6-months later, but only among individuals who also had alexithymia scores above 60.5. Taking alexithymia severity into consideration during treatment planning may help optimize the effectiveness of interventions. These results show merit for future research to consider alexithymia as a variable that could potentially impact outcomes among individuals with co-occurring depression and hazardous alcohol use.

Computer-Based Training for Cognitive Behavioural Therapy for Substance Use Disorder: A Randomized Controlled Trial Including Quantitative and Qualitative Health and Economic Outcomes: Formation informatisée pour la thérapie cognitivo-comportementale pour les troubles liés à l'usage de substances : un essai randomisé contrôlé y compris les résultats quantitatifs et qualitatifs en matière de santé et d'économie.

OBJECTIVES: Heavy alcohol and drug use is reported by a substantial number of Canadians; yet, only a minority of those experiencing substance use difficulties access specialized services. Computer-Based Training for Cognitive Behavioural Therapy (CBT4CBT) offers a low-cost method to deliver accessible and high-quality CBT for substance use difficulties. To date, CBT4CBT has primarily been evaluated in terms of quantitative outcomes within substance use disorder (SUD) samples in the United States. A comparison between CBT4CBT versus standard care for SUDs in a Canadian sample is critical to evaluate its potential for health services in Canada. We conducted a randomized controlled trial of CBT4CBT versus standard care for SUD. METHODS: Adults seeking outpatient treatment for SUD (N = 50) were randomly assigned to receive either CBT4CBT or treatment-as-usual (TAU) for 8 weeks. Measures of substance use and associated harms and quality of life were completed before and after treatment and at 6-month follow-up. Qualitative interviews were administered after treatment and at follow-up, and healthcare utilization and costs were extracted for the entire study period. RESULTS: Participants exhibited improvements on the primary outcome as well as several secondary outcomes; however, there were no differences between groups. A cost-effectiveness analysis found lower healthcare costs in CBT4CBT versus TAU in a subsample analysis, but more days of substance use in CBT4CBT. Qualitative analyses highlighted the benefits and challenges of CBT4CBT. DISCUSSION: Findings supported an overall improvement in clinical outcomes. Further investigation is warranted to identify opportunities for implementation of CBT4CBT in tertiary care settings.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03767907.

Evaluating a digital intervention targeting substance use difficultiesPlain Language SummaryWhy was the study done?Heavy alcohol and drug use is frequent in the Canadian population, although very few people have access to treatment. The digital intervention, Computer-Based Training for Cognitive Behavioural Therapy (CBT4CBT), may provide a low-cost, high-quality, and easily accessible method of treatment for substance use difficulties. Limited research on this digital intervention has been conducted in Canadian populations, and few studies thus far have evaluated participants' subjective experience using the intervention, along with the cost on the Canadian healthcare system.What did the researchers do?The research team recruited participants and provided access to either CBT4CBT or to standard care at a mental health hospital for 8 weeks. Participants were asked questions about their substance use and related consequences, quality of life, and thoughts on the treatment they received. Information regarding healthcare use and the cost to the healthcare system was also gathered.What did the researchers find?Participants in both groups improved with regards to their substance use, some related consequences, and psychological quality of life. Participants provided insight on the benefits and challenges of both types of treatment. It was also found that the CBT4CBT intervention was less costly.What do these findings mean?These findings support that adults receiving CBT4CBT and standard care both improved to a similar degree in this sample. Participant feedback may inform future studies of how best to implement this intervention in clinical studies. Future studies with larger samples are needed to further examine whether CBT4CBT can increase access to supports and be beneficial in the Canadian healthcare system.

Detecting critical transition signals from single-cell transcriptomes to infer lineage-determining transcription factors.

Analyzing single-cell transcriptomes promises to decipher the plasticity, heterogeneity, and rapid switches in developmental cellular state transitions. Such analyses require the identification of gene markers for semi-stable transition states. However, there are nontrivial challenges such as unexplainable stochasticity, variable population sizes, and alternative trajectory constructions. By advancing current tipping-point theory-based models with feature selection, network decomposition, accurate estimation of correlations, and optimization, we developed BioTIP to overcome these challenges. BioTIP identifies a small group of genes, called critical transition signal (CTS), to characterize regulated stochasticity during semi-stable transitions. Although methods rooted in different theories converged at the same transition events in two benchmark datasets, BioTIP is unique in inferring lineage-determining transcription factors governing critical transition. Applying BioTIP to mouse gastrulation data, we identify multiple CTSs from one dataset and validated their significance in another independent dataset. We detect the established regulator Etv2 whose expression change drives the haemato-endothelial bifurcation, and its targets together in CTS across three datasets. After comparing to three current methods using six datasets, we show that BioTIP is accurate, user-friendly, independent of pseudo-temporal trajectory, and captures significantly interconnected and reproducible CTSs. We expect BioTIP to provide great insight into dynamic regulations of lineage-determining factors.

Return to sports following discectomy: does a consensus exist?

INTRODUCTION: In the USA, lumbar discectomy is one of the most commonly performed spinal procedures. As certain sports are considered to be major risk factors for disc herniation, the question remains as to when highly active patients should return to their previous level of activity. This study aimed to analyze spine surgeons' opinions on when patients may return to activities following discectomy as well as their underlying rationale for their decision. METHODS: A questionnaire was designed by five different fellowship-trained spine surgeons for the 168 members of the Spine Society of Australia. Questions on the surgeons experience, decision making, preferred surgical technique, the postoperative rehabilitation and the response to patient expectations were included. RESULTS: In total, 83.9% of surgeons discuss the postoperative level of activity with their patients. Sport is considered as an important contributor for good functional outcome by 71.0% of surgeons. Surgeons recommend avoiding, often permanently, weightlifting (35.7%) of the time, rugby (21.4%), horseback riding (17.9%) as well as martial arts (14.3%) postoperatively even with previous training. The return to high levels of activity is considered as a major risk factor for disc herniation recurrence by 25.8% of surgeons. Return to high level of activity is typically recommended after 3 months by 48.4% of surgeons. CONCLUSION: So far no consensus on the rehabilitation protocol and return to level of activity exists. Recommendations depend on personal experience as well as the individuals' training, and typically, a period of avoidance of sport for up to 3 months is recommended. LEVEL OF EVIDENCE: Level III, therapeutic and prognostic study.

Atypical Wenckebach without grouped beating due to dual AV nodal conduction.

A 31-year-old woman reported dizziness in the early postpartum period after receiving dexmedetomidine. The ECG was misinterpreted as complete heart block; however, more careful analysis revealed an atypical Wenckebach pattern with dual AV nodal conduction and termination of nonconducted P waves with junctional escape beats. The patient's rhythm returned to sinus after stopping dexmedetomidine. Atypical Wenckebach patterns account for greater than 50% of patients with Mobitz Type I AV block and can be misinterpreted as high-grade AV block. This case highlights the causes of atypical Wenckebach patterns and how careful analysis of intervals can help clinicians avoid misdiagnosis.

Assessing the Prevalence of Cannabis Use Through a Survey About Criminal Activity Versus One About Alcohol, Tobacco, and Other Drugs.

Background: The prevalence of cannabis use in the United Kingdom might be underestimated using the Crime Survey of England and Wales. The current study examined whether responding to questions about their cannabis use as part of a crime survey would be less likely to report that they use cannabis compared to those responding to the same questions that are part of a survey about health. Methods: Participants were randomized to be told that the items about cannabis use came from a crime survey versus from a health survey. In addition, the sample was recruited using a representative online sampling method and compared to published rates of self-reported cannabis use collected as part of the Crime Survey for England and Wales. Results: There was no significant difference (p > 0.05) in the proportion endorsing cannabis use between those told the items came from a crime survey versus a health survey. However, self-reported rates of cannabis use collected as part of the online panel (51.3% ever use; 11.9% past year; age range 18-64 years) appeared higher than those reported based on results from the Crime Survey for England and Wales (37.2% ever and 5.8% past year; age range 18-59 years). Conclusion: The current study did not find evidence that manipulating whether participants were told that the items asking about cannabis use came from a survey asking about criminal activity versus one about health had an impact on self-reported cannabis use. However, as prevalence estimates generated by the Crime Survey of England and Wales do appear to be an underestimate of actual levels of cannabis use in the United Kingdom, further research is merited on this topic.

Perceptions of the Seriousness of Different Addictive Behaviors in the United Kingdom.

Background: Societal beliefs about the seriousness of different addictions were assessed in the United Kingdom (UK). Methods: An online panel, conducted in 2021 and sampled to be representative of the UK general population 18 years and over (N = 1499), was conducted and asked participants their views regarding the seriousness of different societal problems, including various addictive behaviors. Results: Cannabis was ranked as the least serious of the addictive behaviors. Other illicit drug use (cocaine, amphetamine, heroin) was rated as the most serious of addictive behaviors. None of the addictive behaviors were rated as being as serious a problem to society as environmental damage, violent crime, poverty, and the COVID-19 pandemic. Conclusions: Ratings of cannabis use were not as expected and stand in contrast to the current UK policy on cannabis use. In addition, the UK policy on alcohol consumption contrasts with societal concerns about alcohol use.

Examining Changes in Quality of Life as an Outcome Measure in Three Randomized Controlled Trials of Online Interventions That Included an Intervention for Hazardous Alcohol Use.

BACKGROUND: Quality of life (QOL) summarizes an individual's perceived satisfaction across multiple life domains. Many factors can impact this measure, but research has demonstrated that individuals with addictions, physical, and mental health concerns tend to score lower than general population samples. While QOL is often important to individuals, it is rarely used by researchers as an outcome measure when evaluating treatment efficacy. METHODS: This secondary analysis used data collected during three separate randomized controlled trials testing the efficacy of different online interventions to explore change in QOL over time between treatment conditions. The first project was concerned with only alcohol interventions. The other two combined either a gambling or mental health intervention with a brief alcohol intervention. Males and females were analyzed separately. RESULTS: This analysis found treatment effects among female participants in two projects. In the project only concerning alcohol, female quality of life improved more among those who received an extensive intervention for hazardous alcohol use compared to a brief intervention (p = .029). QOL among females who received only the mental health intervention improved more than those who also received a brief alcohol intervention (p = .049). CONCLUSION: Poor QOL is often cited as a reason individuals decide to make behavior changes, yet treatment evaluations do not typically consider this patient-important outcome. This analysis found some support for different treatment effects on QOL scores in studies involving at least one intervention for hazardous alcohol use.

Applying the Canadian Low-Risk Gambling Guidelines to Gambling Harm Reduction in England.

There is a need for evidence-based guidelines for gamblers who wish to reduce their risk of harm by setting self-directed limits on their gambling. Recognizing this, the Canadian Low-Risk Gambling Guidelines were developed using data from 8 countries to establish the relationship between gambling behaviour and harm. The guidelines include recommended limits on gambling spending as a percentage of income, gambling frequency, and number of types of games played. However, the developers of the LRGG's did not include UK data in their analysis. This study analyzes data from Health Survey England to assess the applicability of the Canadian Low-Risk Gambling Guidelines to gamblers in England. Using HSE data from 2016 to 2018, we generated risk curves for the relationship between 2 dimensions of gambling behaviour-frequency of gambling sessions and number of types of games played-and gambling harm. We defined harm as a score of 1 or above on the Problem Gambling Severity Index. HSE does not include questions on gambling spending, therefore this was not assessed. The relationship observed between frequency and types of gambling and harm among HSE respondents was similar to the risk curves generated for the development of the Canadian LRGG's. Gamblers in England who gambled twice weekly or more, or who played 3 or more types of games, were significantly more likely to experience harm from gambling than those who gambled below these limits. The Canadian LRGG's may potentially be applied to gambling harm reduction efforts in England. More research is needed to determine the acceptability of these guidelines to people who gamble in England.

The clinical and radiographic degenerative spondylolisthesis classification and its predictive value.

INTRODUCTION: The clinical and radiographic degenerative spondylolisthesis (CARDS) classification is a new classification that has been introduced for degenerative spondylolisthesis (DS). It has four categories. Our study aimed to analyse the functional and radiographic outcome following DS surgery based on the preoperative CARDS classification. METHODS: A retrospective study of the prospectively collected Australian Spine Registry database was performed. Data on demographics, patient reported outcome measures including the Oswestry Disability Index (ODI) and EQ-5D-3 L scores, and changes in radiographic measurements were analysed. Based on the preoperative findings all x-rays were classified applying the CARDS classification. RESULTS: Between 2018 and 2021 a total of 54-patients were identified as having had surgery for DS at L4/5. The mean age was 65.3 ± 11.3years and females were predominantly affected (61%). Most cases were of CARDS type C (46%), followed by type B (29%). CARDS type A and D were observed in 18% and 6% respectively. Preoperatively, the L4/5 lordosis was 19.8 ± 6.3° and lumbar lordosis 43.9 ± 12.8°. Postoperatively the L4/5 lordosis alignment changed significantly to 23.5 ± 8.8° (p < 0.05). Preoperatively, the CARDS classification was 34.8 ± 17.4 (type A), 40.5 ± 11.0 (type B), 43.8 ± 12.9 and 50.0 ± 14.4 for type D (Pearson-coefficient 0.284, p = 0.041). Postoperatively this changed to 22.7 ± 16.1, 28.7 ± 21.2, 12.5 ± 13.1, and 6.5 ± 2.1 respectively. Similar improvements were observed for the EQ-5D-3 L. CONCLUSION: This study shows that the CARDS classification correlates with preoperative functional scores as well as helping to predict response to surgery. CARDS will likely assist in operative planning and prognostication. LEVEL OF EVIDENCE: III, therapeutic and prognostic study.

Efficient free-space to on-chip coupling of THz-bandwidth pulses for biomolecule fingerprint sensing.

Wide bandwidth THz pulses can be used to record the distinctive spectral fingerprints related to the vibrational or rotational modes of polycrystalline biomolecules, and can be used to resolve the time-dependent dynamics of such systems. Waveguides, owing to their tight spatial confinement of the electromagnetic fields and the longer interaction distance, are promising platforms with which to study small volumes of such systems. The efficient input of sub-ps THz pulses into waveguides is challenging owing to the wide bandwidth of the THz signal. Here, we propose a sensing chip comprised of a pair of back-to-back Vivaldi antennas feeding into, and out from, a 90° bent slotline waveguide to overcome this problem. The effective operating bandwidth of the sensing chip ranges from 0.2 to 1.15 THz, and the free-space to on-chip coupling efficiency is as high as 51% at 0.44 THz. Over the entire band, the THz signal is ∼42 dB above the noise level at room temperature, with a peak of ∼73 dB above the noise. In order to demonstrate the use of the chip, we have measured the characteristic fingerprint of α-lactose monohydrate, and its sharp absorption peak at ∼0.53 THz was successfully observed, demonstrating the promise of our technique. The chip has the merits of efficient in-plane coupling, ultra-wide bandwidth, ease-of-integration, and simple fabrication. It has the potential for large-scale manufacture, and can be a strong candidate for integration into other THz light-matter interaction platforms.

Disentangling Medicinal and Recreational cannabis Use Among People Living with HIV: An Ecological Momentary Assessment Study.

This study examined the feasibility of using ecological momentary assessment (EMA) to disentangle medicinal cannabis use (MCU) from recreational cannabis use (RCU) among people living HIV (PLWH). Over a 14-day period, PLWH (N = 29) who engaged in both MCU and RCU completed a smartphone-based survey before and after every cannabis use event assessing general motivation for cannabis use (MCU-only, RCU-only, or mixed MCU/RCU), cannabis use behavior, and several antecedents and outcomes of cannabis use. A total of 739 pre-cannabis surveys were completed; 590 (80%) of the prompted post-cannabis surveys were completed. Motives for cannabis use were reported as MCU-only on 24%, RCU-only on 30%, and mixed MCU/RCU on 46% of pre-cannabis surveys. Mixed effects models examined within-person differences across MCU-only, RCU-only, and mixed MCU/RCU events. Results showed that relative to RCU-only events, MCU-only events were more likely to involve symptom management and drug substitution motives, physical and sleep-related symptoms, solitary cannabis use, and use of cannabis oils and sprays; MCU-only events were less likely to involve relaxation, happiness, and wellness motives, cannabis flower use, and positive cannabis consequences. Differences between mixed MCU/RCU and RCU-only events were similar, except that mixed MCU/RCU events were additionally associated with stress reduction motives and symptoms of anxiety and depression. Findings support the feasibility of partially disentangling MCU and RCU behavior among PLWH who engage in concurrent MCU and RCU. This study highlights the need for more EMA studies isolating MCU from RCU to inform ongoing changes to cannabis policies.

Knowledge of Cannabinoid Content Among People Living with HIV Who Use Cannabis: a Daily Diary Study.

BACKGROUND: Many people living with HIV (PLWH) use cannabis for medicinal reasons. Patients' knowledge of the tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations of the cannabis products they use may be important in helping patients achieve symptom relief while guarding against potential risks of cannabis use. However, no studies have examined cannabinoid concentration knowledge among PLWH. METHOD: PLWH (N = 29; 76% men, mean age 47 years) reporting cannabis use for both medicinal and nonmedicinal reasons completed daily surveys over 14 days assessing cannabis products used, knowledge of cannabinoid concentrations of cannabis products used, cannabis use motives (medicinal, nonmedicinal, both), and positive and negative cannabis-related consequences. Across the 361 cannabis use days captured on the daily surveys, at least some knowledge of cannabinoid concentrations was reported on an average of 43.1% (for THC) and 26.6% (for CBD) of the days. RESULTS: Generalized linear mixed models revealed that participants were more likely to report knowing THC and CBD concentrations on days when they used non-flower forms of cannabis relative to days when they used cannabis flower only. Participants who used cannabis for medicinal reasons on a greater proportion of days had greater knowledge of cannabinoid concentration overall across days. Further, greater overall knowledge of cannabinoid concentrations was associated with fewer reported negative cannabis-related consequences. CONCLUSIONS: Findings suggest that among PLWH, knowledge of cannabinoid concentrations may be higher when using non-flower cannabis products and among those reporting primarily medicinal cannabis use. Moreover, knowledge of cannabinoid concentration may protect against negative cannabis-related consequences in this population.

Exertional Rhabdomyolysis in Athletes: Systematic Review and Current Perspectives.

OBJECTIVE: Exertional rhabdomyolysis results from a breakdown of skeletal muscle cells after intense exercise in otherwise healthy patients, causing increased levels of creatine kinase (CK) or myoglobin, as well as urine dipstick positive for blood, and may result in kidney insufficiency. The aim of this study was to outline the current perspectives of exertional rhabdomyolysis in athletes and subsequent treatment based on the current literature. DATA SOURCES: We searched the MEDLINE/PubMed and Google databases for ([exercise] OR [exertional]) AND rhabdomyolysis following the PRISMA guidelines. All abstracts were reviewed by 2 independent examiners. Inclusion criteria consisted of original articles presenting studies on exertional rhabdomyolysis or exercise-induced rhabdomyolysis with 7 or more cases. All case reports, case series, or editorials were excluded. MAIN RESULTS: A total of 1541-abstracts were screened, leaving 25 studies for final inclusion and analysing 772patients. Especially, young male patients were affected at a mean age of 28.7 years (range 15.8-46.6 years). Most of the athletes performed running, including marathons in 54.3% of cases (n = 419/772), followed by weightlifting in 14.8% (n = 114/772). At the time of presentation, the mean creatine kinase was 31 481 IU/L (range 164-106,488 IU/L). Seventeen studies reported the highest level of CK, which was 38 552 IU/L (range 450-88,496 IU/L). For treatment, hydration was the most common method of choice reported by 8 studies. CONCLUSIONS: Exertional rhabdomyolysis seems to be underestimated, and it is essential to screen patients who present with muscle soreness/cramps and/or dark urine after heavy endurance events to avoid any further complications. LEVEL OF EVIDENCE: II; systematic review.

Evaluating a Blended Learning Model for Medical Student ECG Teaching.

OBJECTIVES: The ability to interpret a 12-lead electrocardiogram (ECG) is an essential skill in inpatient and outpatient settings. In medical school, this skill is generally taught during the Internal Medicine clerkship. Blended learning is a pedagogical tool that combines different modes of information delivery, models of teaching, and learning styles combining face-to-face learning sessions with online learning. The objectives of this study were to develop a curriculum using a blended educational model including lecture, focused educational videos, flipped classroom, and team-based learning to teach a systematic approach to ECG interpretation and enhance the ability of students to identify common and life-threatening electrocardiographic abnormalities. METHODS: Between 2016 and 2019, 349 medical students from the University of Colorado School of Medicine received the blended learning curriculum, which included an introductory lecture followed by five 30-minute sessions. These sessions encompassed preclass videos and team-based learning in a flipped-classroom design covering critical concepts in electrocardiography. A sample of 64 students completed a survey evaluating confidence in ECG interpretation skills before and after the curriculum. All of the students completed a 17-item pretest and posttest. RESULTS: The new curriculum improved learner confidence in ECG interpretation (Wilcoxon signed rank-sum test, P < 0.001). Postcurriculum test scores showed statistically significant improvement in all of the diagnoses tested (paired Student t test, P < 0.01), the most significant gains occurring in the life-threatening tracings of ventricular fibrillation and in ventricular tachycardia. CONCLUSIONS: Using a blended learning model with multiple educational modalities resulted in significant improvement in learners' performance and confidence in ECG interpretation.

Spinal fractures in fused spines: nonoperative treatment is a reliable alternative.

INTRODUCTION: Spinal fractures in fused spines such as in ankylosing spondylitis or DISH are typically of type B or C fractures where operative treatment is recommended. The mortality rate in non-operatively treated patients is reported to be 51%. The purpose of this study was to investigate the mortality rate, complication rate and demographics of patients following non-operatively treatment in fused spine injuries. METHODS: Between 2019 and 2021, a retrospective study was conducted including all patients who presented to our trauma center with a spinal fracture of a fused spine. Radiology and patient charts were analyzed for fracture pattern, complications, neurological deficit, comorbidities, and mortality rate. RESULTS: A total of 49 patients were found at a mean age was 79.8 ± 10.9 years and primarily males were affected in 65.3%. All fractures were of type B and the thoracic spine was involved in 85.7%. The mean follow-up was 6.3 ± 8.2 months and fusion was obtained in all patients. No neurological deficit was observed in any. A total of 13 patients died at a mean age of 86.5 ± 10.0 years after 157.1 ± 158.1 days. 6 patients (10.2%) deceased within the first 6 weeks at a mean age of 91.8 ± 3.8 years. One patient each suffered from heart failure, an acute delirium, end stage colon cancer and subdural hemorrhage. CONCLUSION: This study shows that the mortality rate in the first 6 weeks following a fracture in a fused spine is 10.2% for patients above the age of 90 years. Therefore, non-operative treatment should be taken into consideration as the mortality rate in other studies may be overestimated. LEVEL OF EVIDENCE: III, retrospective study.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).