Test Characteristics of Emergency Medicine-Performed Point-of-Care Ultrasound for the Diagnosis of Acute Cholecystitis: A Systematic Review and Meta-analysis.

Acute cholecystitis accounts for up to 9% of hospital admissions for acute abdominal pain, and best practice entails early surgical management. Ultrasound is the standard modality used to confirm diagnosis. Our objective was to perform a systematic review and meta-analysis to determine the diagnostic accuracy of emergency physician-performed point-of-care ultrasound for the diagnosis of acute cholecystitis when compared with a reference standard of final diagnosis (informed by available surgical pathology, discharge diagnosis, and radiology-performed ultrasound). We completed a systematic review and meta-analysis, registered in PROSPERO, in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched 7 databases as well as gray literature in the form of select conference abstracts from inception to February 8, 2023. Two independent reviewers completed study selection, data extraction, and risk of bias (QUADAS-2) assessment. Disagreements were resolved by consensus with a third reviewer. Data were extracted from eligible studies to create 2 × 2 tables for diagnostic accuracy meta-analysis. Hierarchical Summary Receiver Operating Characteristic models were constructed. Of 1855 titles/abstracts, 40 were selected for full-text review. Ten studies (n=2356) were included. Emergency physician-performed point-of-care ultrasound with final diagnosis as the reference standard (7 studies, n=1,772) had a pooled sensitivity of 70.9% (95% confidence interval [CI] 62.3 to 78.2), specificity of 94.4% (95% CI 88.2 to 97.5), positive likelihood ratio of 12.7 (5.8 to 27.5), and negative likelihood ratio of 0.31 (0.23 to 0.41) for the diagnosis of acute cholecystitis. Emergency physician-performed point-of-care ultrasound has high specificity and moderate sensitivity for the diagnosis of acute cholecystitis in patients with clinical suspicion. This review supports the use of emergency physician-performed point-of-care ultrasound to rule in a diagnosis of acute cholecystitis in the emergency department, which may help expedite definitive management.

Use of point-of-care ultrasound in rural British Columbia: Scale, training, and barriers.

OBJECTIVE: To determine the scale and scope of use of point-of-care ultrasound (POCUS) in rural British Columbia (BC). DESIGN: Online survey. SETTING: Rural BC. PARTICIPANTS: Physicians practising in rural BC communities. MAIN OUTCOME MEASURES: Practitioner demographic and practice characteristics, locations and frequency of POCUS use, POCUS education and training, and practitioner attitudes about and barriers to POCUS use. RESULTS: Two hundred twenty-seven surveys were completed in fall 2021, corresponding to a response rate of 11.9% of all rural practitioners in BC. A total of 52.1% of respondents worked in communities with less than 10,000 people, while 24.9% had practices with relatively large proportions of Indigenous patients (more than 20% of the practice population). Respondents reported ease of access to local POCUS devices, with use highest in emergency departments (87.2%) followed by ambulatory care clinic (54.7%) and inpatient (50.3%) settings. Use of POCUS influenced clinical decision making in half the occasions in which it was employed, including a range of diagnostic and procedural applications. Barriers to use included lack of training, limited time to perform POCUS scans, and absence of image review or consultative support. Needed support for POCUS identified by respondents included real-time image acquisition advice and funding for both device acquisition and training. Recommendations for including POCUS training in undergraduate and residency education were strongly supported. CONCLUSION: Use of POCUS in BC is expanding in frequency, scope, and scale in practices serving rural areas and in rural communities with large Indigenous populations, with practitioners reporting important improvements in clinical care as a result. Future research could help improve systemic support for POCUS use, guide needed curriculum changes in medical school and postgraduate training, and be used to inform continuing professional development needs.

Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor.

Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.

EFSUMB Clinical Practice Guidelines for Point-of-Care Ultrasound: Part One (Common Heart and Pulmonary Applications) SHORT VERSION.

OBJECTIVE: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS). METHODS: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. FINDINGS AND RECOMMENDATIONS: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). CONCLUSION: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.

EFSUMB Clinical Practice Guidelines for Point-of-Care Ultrasound: Part One (Common Heart and Pulmonary Applications) LONG VERSION.

AIMS: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS). METHODS: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. FINDINGS AND RECOMMENDATIONS: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). CONCLUSION: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.

RUNX Binding Sites Are Enriched in Herpesvirus Genomes, and RUNX1 Overexpression Leads to Herpes Simplex Virus 1 Suppression.

Herpes simplex virus 1 (HSV-1) and HSV-2 can efficiently establish lifelong, transcriptionally silent latency states in sensory neurons to escape host detection. While host factors have previously been associated with long-range insulators in the viral genome, it is still unknown whether host transcription factors can repress viral genes more proximately to promote latency in dorsal root ganglion (DRG) neurons. Here, we assessed whether RUNX (runt-related transcription factor) transcription factors, which are critical in the development of sensory neurons, could be binding HSV-1 genome directly to suppress viral gene expression and lytic infection. Using previously published transcriptome sequencing data, we confirmed that mouse DRG neurons highly express Runx1 mRNA. Through computational analysis of HSV-1 and HSV-2 genomes, we observed that putative RUNX consensus binding sites (CBSs) were more enriched and more closely located to viral gene transcription start sites than would be expected by chance. We further found that RUNX CBSs were significantly more enriched among genomes of herpesviruses compared to those of nonherpesviruses. Utilizing an in vitro model of HSV-1 infection, we found that overexpressed RUNX1 could bind putative binding sites in the HSV-1 genome, repress numerous viral genes spanning all three kinetic classes, and suppress productive infection. In contrast, knockdown of RUNX1 in neuroblastoma cells induced viral gene expression and increased HSV-1 infection in vitro In sum, these data support a novel role for RUNX1 in directly binding herpesvirus genome, silencing the transcription of numerous viral genes, and ultimately limiting overall infection.IMPORTANCE Infecting 90% of the global population, HSV-1 and HSV-2 represent some of the most prevalent viruses in the world. Much of their success can be attributed to their ability to establish lifelong latent infections in the dorsal root ganglia (DRG). It is still largely unknown, however, how host transcription factors are involved in establishing this latency. Here, we report that RUNX1, expressed highly in DRG, binds HSV-1 genome, represses transcription of numerous viral genes, and suppresses productive in vitro infection. Our computational work further suggests this strategy may be used by other herpesviruses to reinforce latency in a cell-specific manner.

The physical examination is unreliable in determining the location of the distal fibular physis.

OBJECTIVES: Salter-Harris type 1 (SH1) fractures of the distal fibula are acute orthopedic injuries with tenderness over the physis without radiographic evidence of fracture. Our primary objective was to establish the accuracy of the physical examination performed by pediatric emergency medicine (PEM) physicians in determining the location of the distal fibular physis compared to a criterion standard of ultrasound. METHODS: This was a prospective, observational study at an urban academic pediatric emergency department of a convenience sample of children aged 4 to 10 years old between March 2019 and March 2020. A PEM physician or fellow examined the patient's distal fibula and marked the location of the physis with a marker. A study investigator scanned the distal fibula to establish the location of the physis on ultrasound and measured the distance between the clinician's estimated position and the actual sonographic position. We a priori defined a clinically accurate position as a distance of ≤5 mm. We compared the accuracy rate of physical examination to ultrasound landmarking using proportions with 95% confidence intervals (CI). RESULTS: We enrolled 71 patients, of whom 52 (73%) were male. The mean age was 6.7 years and the mean weight was 25.5 kg. Participating PEM physicians included 18 attending physicians and 2 fellows. The distal fibular physis was correctly identified in 24 patients, yielding an accuracy rate of 34% (95% CI 23%-46%). The mean distance between the physician's estimated position and the sonographic position was 7.4 mm (95% CI 6.4-8.4 mm). CONCLUSIONS: PEM physicians were unable to accurately identify the distal fibular physis on physical examination.

The effect of patient positioning on ultrasound landmarking for cricothyrotomy.

PURPOSE: Our primary objective was to assess the difference in position of the ultrasound-guided landmark of the cricothyroid membrane (CTM) when performed with the supine patient positioned at different head of bed (HOB) elevations. METHODS: In this prospective observational study of patients presenting to the emergency department with non-life-threatening complaints, subjects underwent ultrasound-guided landmarking of the CTM with HOB elevation at 0°, 30°, and 90°. A linear mixed effects regression model was used to assess the change in the CTM landmark associated with head position. We used a second adjusted linear mixed effects model to assess possible confounding patient factors associated with these changes. RESULTS: One-hundred and ten patients were enrolled, with a median [interquartile range] age of 39 [29-59] yr and 51:49 female:male ratio. Head of bed elevation at 30° and 90° resulted in a cephalad change in the CTM landmark of 2.7 mm (99% confidence interval [CI], 1.7 to 3.8; P < 0.001) and 4.2 mm (99% CI, 3.2 to 5.3; P < 0.001) respectively compared with the landmark at 0°. Body mass index (BMI) was associated with a change of 4.6 mm (99% CI, 0.5 to 8.7; P = 0.004) for BMI ≥ 30 compared with < 18.5 kg·m-2 The impact of patient age on distance depended on HOB elevation, where patients > 70 yr had a change of 2.6 mm (99% CI, 0.01 to 5.1; P = 0.009) at 90° HOB elevation compared with 30°. CONCLUSION: The location of the ultrasound-identified surface landmark of the CTM moves in a cephalad direction by changing the position of the HOB from supine 0° to elevation at 30° and 90°. This may be clinically important when attempting cricothyrotomy using a percutaneous (blind) technique, particularly when CTM identification and cricothyrotomy are performed at different head elevations.

RéSUMé: OBJECTIF: Notre objectif principal était d'évaluer la différence de position de la membrane cricothyroïdienne en tant que repère échoguidé selon qu'elle est identifiée à différentes élévations de la tête du lit avec le patient en décubitus dorsal. MéTHODE: Cette étude observationnelle prospective a inclus des patients se présentant à l'urgence pour des problèmes de santé ne mettant pas leur vie en danger. Les repères échoguidés de la membrane cricothyroïdienne ont été identifiés chez ces patients en positionnant la tête de lit à 0°, 30° et 90°. Un modèle de régression linéaire à effets mixtes a été utilisé pour évaluer les modifications du repère de la membrane cricothyroïdienne associés à la position de la tête. Nous avons utilisé un deuxième modèle linéaire à effets mixtes ajustés pour évaluer les facteurs confondants potentiels liés au patient et associés à ces changements. RéSULTATS: Cent dix patients ont été recrutés, d'un âge médian [écart interquartile] de 39 [29-59] ans et avec un ratio femmes : hommes de 51 : 49. L'élévation de la tête de lit à 30° et 90° a entraîné un glissement céphalade de 2,7 mm (intervalle de confiance [IC] 99 %, 1,7 à 3,8; P < 0,001) et de 4,2 mm (IC 99 %, 3,2 à 5,3; P < 0,001) du marquage de la membrane cricothyroïdienne, respectivement, comparativement au repère identifié à un angle de 0°. L'indice de masse corporelle (IMC) était associé à un changement de 4,6 mm (IC 99 %, 0,5 à 8,7; P = 0,004) pour un IMC ≥ 30, comparativement à < 18,5 kg·m−2. L'impact de l'âge du patient sur la distance dépendait de l'élévation de la tête de lit : chez les patients > 70 ans, le changement était de 2,6 mm (IC 99 %, 0,01 à 5,1; P = 0,009) à une élévation de la tête de lit de 90° comparativement à un angle de 30°. CONCLUSION: L'emplacement du repère de surface identifié par échoguidage de la membrane cricothyroïdienne se déplace en direction céphalade lorsqu'on change la position de la tête de lit d'un décubitus dorsal à 0° à une élévation de 30° et 90°. Cela pourrait avoir une importance clinique lors d'une tentative de cricothyrotomie à l'aide d'une technique percutanée (en aveugle), particulièrement si l'identification de la membrane cricothyroïdienne et la cricothyrotomie sont réalisées à différentes élévations de la tête.

A systematic review and meta-analysis of long-term reintervention after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Patients who undergo endovascular aneurysm repair (EVAR) often require reintervention after the index repair. The long-term rate of reintervention and how this has changed with newer device technology are poorly understood. Therefore, we performed a systematic review and meta-analysis of the available literature to determine long-term freedom from reintervention after EVAR and the change in reintervention rates over time. METHODS: We performed a systematic review of MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials and observational studies that documented the rate of reintervention after EVAR. We performed a meta-analysis of Kaplan-Meier freedom from reintervention at each year after EVAR. We used linear regression to evaluate change in reintervention rate over time with newer device technology. RESULTS: We included a total of 30 studies (randomized trials, n = 3; observational studies, n = 27) comprising 32,126 patients in this review and meta-analysis. Studies ranged in the implantation date of the EVAR device from 1996 to 2014. The probability of freedom from reintervention was 81% (95% confidence interval [CI], 77%-85%) at 5 years, 70% (95% CI, 65%-76%) at 10 years, and 64% (95% CI, 46%-79%) at 14 years. Linear regression demonstrated an improvement in freedom from reintervention when results were stratified by the year of device implantation. At 1 year, estimated freedom from reintervention improved from 90% in 1998 to 94% in 2008 (n = 26 studies; R2 = 0.11; P = .10). At three years, estimated freedom from reintervention improved from 77% in 1998 to 90% in 2008 (n = 26 studies; R2 = 0.27; P = .006). At 5 years, estimated freedom from reintervention improved from 68% in 1998 to 81% in 2008 (n = 22 studies; R2 =0.12; P = .12). At 7 years, estimated freedom from reintervention improved from 51% in 1998 to 86% in 2011 (n = 22 studies; R2 = 0.40; P = .015). CONCLUSIONS: EVAR patients remain at risk for reintervention indefinitely, and therefore lifelong surveillance is imperative. Encouragingly, reintervention rates have improved over time, with newer devices exhibiting lower rates. Reintervention rate remains an important metric for new devices and registries.

Comparing Physical Examination With Sonographic Versions of the Same Examination Techniques for Splenomegaly.

OBJECTIVES: To determine whether sonographic versions of physical examination techniques can accurately identify splenomegaly, Castell's method (Ann Intern Med 1967; 67:1265-1267), the sonographic Castell's method, spleen tip palpation, and the sonographic spleen tip technique were compared with reference measurements. METHODS: Two clinicians trained in bedside sonography patients recruited from an urban hematology clinic. Each patient was examined for splenomegaly using conventional percussion and palpation techniques (Castell's method and spleen tip palpation, respectively), as well as the sonographic versions of these maneuvers (sonographic Castell's method and sonographic spleen tip technique). Results were compared with a reference standard based on professional sonographer measurements. RESULTS: The sonographic Castell's method had greater sensitivity (91.7% [95% confidence interval, 61.5% to 99.8%]) than the traditional Castell's method (83.3% [95% confidence interval, 51.6% to 97.9%]) but took longer to perform [mean ± SD, 28.8 ± 18.6 versus 18.8 ± 8.1 seconds; P = .01). Palpable and positive sonographic spleen tip results were both 100% specific, but the sonographic spleen tip method was more sensitive (58.3% [95% confidence interval, 27.7% to 84.8%] versus 33.3% [95% confidence interval, 9.9% to 65.1%]). CONCLUSIONS: Sonographic versions of traditional physical examination maneuvers have greater diagnostic accuracy than the physical examination maneuvers from which they are derived but may take longer to perform. We recommend a combination of traditional physical examination and sonographic techniques when evaluating for splenomegaly at the bedside.

Longitudinal regret after treatment for low- and intermediate-risk prostate cancer.

BACKGROUND: Prostate cancer patients diagnosed with low- and intermediate-risk disease have several treatment options. Decisional regret after treatment is a concern, especially when poor oncologic outcomes or declines in health-related quality of life (HRQoL) occur. This study assessed determinants of longitudinal decisional regret in prostate cancer patients attending a multidisciplinary clinic and treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), or active surveillance (AS). METHODS: Patients newly diagnosed with prostate cancer at the Walter Reed National Military Medical Center who attended a multidisciplinary clinic were enrolled into a prospective study from 2006 to 2014. The Decision Regret Scale was administered at 6, 12, 24, and 36 months posttreatment. HRQoL was also assessed at regular intervals using the Expanded Prostate Cancer Index Composite and 36-item RAND Medical Outcomes Study Short Form questionnaires. Adjusted probabilities of reporting regret were estimated via multivariable logistic regression fitted with generalized estimating equations. RESULTS: A total of 652 patients met the inclusion criteria (395 RP, 141 EBRT, 41 BT, 75 AS). Decisional regret was consistently low after all of these treatments. In multivariable models, only African American race (odds ratio, 1.67; 95% confidence interval, 1.12-2.47) was associated with greater regret across time. Age and control preference were marginally associated with regret. Regret scores were similar between RP patients who did and did not experience biochemical recurrence. Declines in HRQoL were weakly correlated with greater decisional regret. CONCLUSION: In the context of a multidisciplinary clinic, decisional regret did not differ significantly between treatment groups but was greater in African Americans and those reporting poorer HRQoL. Cancer 2017;123:4252-4258. © 2017 American Cancer Society.

Validation of a Low-cost Optic Nerve Sheath Ultrasound Phantom: An Educational Tool.

OBJECTIVE: To validate an ocular phantom as a realistic educational tool utilizing in vivo and phantom optic nerve sheath (ONS) images obtained by ultrasound. METHODS: This prospective study enrolled 51 resident physicians from the Denver Health Residency in Emergency Medicine (EM) and 10 ultrasound fellowship-trained EM attending physicians. Participants performed optic nerve sheath diameter (ONSD) measurements on five in vivo and five phantom ocular ultrasound images and rated the realism of each image on a 5-point Likert scale. Chi-square analysis was performed to evaluate the subjective "realness" of in vivo and phantom images. RESULTS: Sixty-one participants performed ONSD measurements. Mean Likert scale values were 3.43 (95% confidence interval: 3.31-3.55) for in vivo images and 3.41 (95% confidence interval: 3.28-3.54) for phantom images. There was no statistical difference in subjective "realness" between in vivo and phantom ONSD ultrasound images among EM residents. Ultrasound fellowship-trained EM attending physicians aptly differentiated between in vivo (p < 0.01) and phantom (p < 0.01) images, as compared with EM residents. CONCLUSION: Our ocular phantom simulates in vivo posterior ocular anatomy. EM resident physicians found the phantom indistinguishable from in vivo images. Our ONS model provides an inexpensive and realistic educational tool to teach bedside ONSD sonography.

Test Characteristics of Emergency Physician-Performed Limited Compression Ultrasound for Lower-Extremity Deep Vein Thrombosis.

BACKGROUND: The current literature suggests that emergency physician (EP)-performed limited compression ultrasound (LCUS) is a rapid and accurate test for deep vein thrombosis (DVT). OBJECTIVE: Our primary objective was to determine the sensitivity and specificity of LCUS for the diagnosis of DVT when performed by a large heterogeneous group of EPs. METHODS: This was a prospective diagnostic test assessment of LCUS conducted at two urban academic emergency departments. The scanning protocol involved compression at the common femoral, superficial femoral, and popliteal veins. Patients were eligible if undergoing radiology department ultrasound of the lower extremity with moderate or high pretest probability for DVT, or low pretest probability for DVT with a positive d-dimer. The enrolling EP performed LCUS before radiology department ultrasound of the same lower extremity. Sensitivity, specificity, and associated 95% confidence intervals (CIs) were calculated with the radiologist interpretation of the radiology department ultrasound as the criterion standard. RESULTS: A total of 56 EPs enrolled 296 patients for LCUS, with a median age of 50 years and 50% female. Fifty (17%) DVTs were identified by radiology department ultrasound, and another five (2%) cases were deemed indeterminate. The sensitivity and specificity of EP-performed LCUS was 86% (95% CI 73-94%) and 93% (95% CI 89-96%), respectively. CONCLUSIONS: A large heterogeneous group of EPs with limited training can perform LCUS with intermediate diagnostic accuracy. Unfortunately, LCUS performed by EPs with limited ultrasound training is not sufficiently sensitive or specific to rule out or diagnose DVT as a single testing modality.