Comparison of transvaginal ultrasound utilization between radiology and point of care ultrasound in first trimester pregnancy.

BACKGROUND: Transvaginal (TVUS) and transabdominal ultrasound (TAUS) are both utilized in the evaluation of early pregnancy patients. While many practitioners using point of care ultrasound (POCUS) will generally not pursue TVUS in cases where an intrauterine pregnancy (IUP) is visualized on TAUS, this may not be true in Radiology performed ultrasound. OBJECTIVES: To evaluate for differences in transvaginal ultrasound (TVUS) utilization between Radiology performed (RP) ultrasound and point of care ultrasound (POCUS) by Emergency Department (ED) physicians in early pregnancy patients. Secondarily, to assess length of stay (LOS) differences and the impact of specialized emergency ultrasound training on TVUS utilization. METHODS: This was a retrospective study at a single academic ED. Study population was all ED patients who underwent first trimester ultrasound during the one year period of March 1, 2021 to February 28, 2022. Variables evaluated were chief complaint, gestational age, LOS, TAUS and TVUS utilization, ultrasound findings, and ultrasound specialty training of the ED physician. RESULTS: There were 133 cases of POCUS ultrasound and 254 cases of RP ultrasound. All cases had TAUS imaging performed. Median LOS for patients when POCUS was utilized was 207 min (IQR 151-294) and 258 min (IQR 208-328) for those only using RP ultrasound, p ≤ 0.001. In the POCUS cohort, 38% (95% CI 30%-46%) received TVUS, while 94% received TVUS in the RP cohort (95% CI 90%-96%), p ≤ 0.001. Patients seen by ED faculty with ultrasound specialty training had TVUS 53% of the time (95% CI 41%-65%), while those seen by other ED faculty had TVUS 79% (95% CI 74%-83%) of the time, p = 0.035. CONCLUSION: POCUS in early pregnancy is associated with a significant reduction in TVUS usage. We suspect that POCUS users elect not to pursue TVUS after an IUP is identified on TAUS, while technicians perform protocol-based TVUS irrespective of TAUS findings. Patients seen by ultrasound trained ED physicians are less likely to receive TVUS.

POINT-OF-CARE ULTRASOUND FOR GUIDANCE OF CLOSED REDUCTION OF FIFTH METACARPAL NECK (BOXER'S) FRACTURE.

BACKGROUND: Ultrasound has been used previously in fracture identification, analgesia delivery, and fracture reduction for patients in the emergency department. It has not been previously described as a tool for the guidance of closed fracture reduction in fifth metacarpal neck fractures ("boxer's fractures"). CASE REPORT: A 28-year-old man presented with hand pain and swelling after punching a wall. Point-of-care ultrasound revealed a significantly angulated fifth metacarpal fracture, which was confirmed with a subsequent hand x-ray study. After an ultrasound-guided ulnar nerve block, closed reduction was performed. Ultrasound was used to assess reduction and ensure improvement in bony angulation during the closed reduction attempts. Post-reduction x-ray study confirmed improved angulation and adequate alignment. Why Should an Emergency Physician Be Aware of This? Point-of-care ultrasound has previously had efficacy in fracture diagnosis and anesthesia delivery for fifth metacarpal fractures. Ultrasound can also be used at the bedside to assist in the determination of adequate fracture reduction when performing closed reduction of a boxer's fracture.

TSABL: Trait Specific Annotation Based Locus predictor.

BACKGROUND: The majority of Genome Wide Associate Study (GWAS) loci fall in the non-coding genome, making causal variants difficult to identify and study. We hypothesized that the regulatory features underlying causal variants are biologically specific, identifiable from data, and that the regulatory architecture that influences one trait is distinct compared to biologically unrelated traits. RESULTS: To better characterize and identify these variants, we used publicly available GWAS loci and genomic annotations to build 17 Trait Specific Annotation Based Locus (TSABL) predictors to identify differences between GWAS loci associated with different phenotypic trait groups. We used a penalized binomial logistic regression model to select trait relevant annotations and tested all models on a holdout set of loci not used for training in any trait. We were able to successfully build models for autoimmune, electrocardiogram, lipid, platelet, red blood cell, and white blood cell trait groups. We used these models both to prioritize variants in existing loci and to identify new genomic regions of interest. CONCLUSIONS: We found that TSABL models identified biologically relevant regulatory features, and anticipate their future use to enhance the design and interpretation of genetic studies.

Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease.

Clinical observations have linked tobacco smoking with increased type 2 diabetes risk. Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes. However, this association could be mediated by additional risk factors correlated with smoking behavior, which have not been investigated. We hypothesized that body mass index (BMI) could help to explain the association between smoking and diabetes risk. First, we confirmed that genetic determinants of smoking initiation increased risk for type 2 diabetes (OR 1.21, 95% CI: 1.15-1.27, P = 1 × 10-12) and coronary artery disease (CAD; OR 1.21, 95% CI: 1.16-1.26, P = 2 × 10-20). Additionally, 2-fold increased smoking risk was positively associated with increased BMI (~0.8 kg/m2, 95% CI: 0.54-0.98 kg/m2, P = 1.8 × 10-11). Multivariable Mendelian randomization analyses showed that BMI accounted for nearly all the risk smoking exerted on type 2 diabetes (OR 1.06, 95% CI: 1.01-1.11, P = 0.03). In contrast, the independent effect of smoking on increased CAD risk persisted (OR 1.12, 95% CI: 1.08-1.17, P = 3 × 10-8). Causal mediation analyses agreed with these estimates. Furthermore, analysis using individual-level data from the Million Veteran Program independently replicated the association of smoking behavior with CAD (OR 1.24, 95% CI: 1.12-1.37, P = 2 × 10-5), but not type 2 diabetes (OR 0.98, 95% CI: 0.89-1.08, P = 0.69), after controlling for BMI. Our findings support a model whereby genetic determinants of smoking increase type 2 diabetes risk indirectly through their relationship with obesity. Smokers should be advised to stop smoking to limit type 2 diabetes and CAD risk. Therapeutic efforts should consider pathophysiology relating smoking and obesity.

High rate of extreme thrombocytosis indicates bone marrow hyperactivity and splenic dysfunction among congenital diaphragmatic hernia patients.

Pediatric extreme thrombocytosis (EXT, platelet count > 1000 x 103/µL) is rare. In a single center retrospective analysis of hospitalized children with EXT, infants with congenital diaphragmatic hernia (CDH) were overrepresented. In general pediatric patients, EXT is usually secondary to infection or inflammation, but most of the 14 CDH patients with EXT had no identifiable inciting factor. Instead, there was evidence that splenic dysfunction and bone marrow hyperactivity underlied EXT in CDH patients. None were associated with bleeding or thrombosis. Our findings identify mechanisms underlying EXT, and aid clinical interpretation and management of EXT in the pediatric population.

Point-of-Care Ultrasound Identifies Pyomyositis Secondary to Intramuscular Testosterone Injection: Report of Two Cases.

BACKGROUND: Intramuscular (i.m.) injections are a commonly utilized route for medication delivery. Intramuscular-associated soft tissue infections are rare and can include pyomyositis and i.m. abscess. Intramuscular testosterone injections have not been previously implicated in causing pyomyositis. Point-of-care ultrasound is an important bedside tool that can identify pyomyositis and differentiate this infection from more common entities such as cellulitis. CASE REPORTS: We present two cases of i.m. testosterone-associated pyomyositis. In both cases, the physical examination features were consistent with simple cellulitis. However, point-of-care ultrasound evaluation revealed changes consistent with pyomyositis in each case. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although uncommon, i.m. injections such as testosterone carry a risk of soft tissue infection. As demonstrated in the above cases, ultrasound can be helpful in making the differentiation between simple cellulitis and pyomyositis. The emergency physician should be cognizant of this complication of therapeutic i.m. injections, as well as the diagnostic efficacy of point-of-care ultrasound in evaluating the extent and location of the soft tissue infection.

A Narrative Review of the Uses of Ultrasound in the Evaluation, Analgesia, and Treatment of Distal Forearm Fractures.

BACKGROUND: Distal forearm fractures are a commonly encountered injury in the emergency department (ED), accounting for 500,000 to 1.5 million visits and 17% of ED fractures. The evaluation and management of these fractures frequently employs x-ray studies, conscious sedation, closed reduction, and splinting. Point-of-care ultrasound (POCUS) can offer significant benefit in the diagnosis and management of these common injuries. OBJECTIVE OF THE REVIEW: To review the clinical utility of POCUS in the diagnosis of distal forearm fractures, as well as to demonstrate the performance of ultrasound-guided analgesia delivery and ultrasound-guided reduction technique. DISCUSSION: The initial evaluation of forearm injuries frequently includes x-ray studies. However, multiple studies have shown ultrasound to be sensitive and specific for distal radius fractures, with the added value of detecting soft tissue injuries missed by conventional radiography. POCUS may also facilitate analgesia through the use of ultrasound-guided hematoma blocks, which removes the need for conscious sedation prior to manipulation. Finally, POCUS can be used after manipulation to assess cortical realignment of the bone fragments and spare the patient multiple reduction attempts and repeat radiographs. CONCLUSION: Distal forearm fractures are common, and the emergency physician should be adept with the evaluation and management of these injuries. POCUS can be a reliable modality in the detection of these fractures and can be used to facilitate analgesia and augment success of reduction attempts. These techniques may decrease length of stay, improve patient pain, and decrease reduction attempts.

Thrombocytosis in an infant with a TRPV4 mutation: a case report.

Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed enhanced proplatelet formation and increased murine platelet count in the context of TRPV4 activation. No prior reports have described platelet count abnormalities in human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4-associated metatropic dysplasia that was lethal in the infantile period.

Tropomyosin 1 genetically constrains in vitro hematopoiesis.

BACKGROUND: Identifying causal variants and genes from human genetic studies of hematopoietic traits is important to enumerate basic regulatory mechanisms underlying these traits, and could ultimately augment translational efforts to generate platelets and/or red blood cells in vitro. To identify putative causal genes from these data, we performed computational modeling using available genome-wide association datasets for platelet and red blood cell traits. RESULTS: Our model identified a joint collection of genomic features enriched at established trait associations and plausible candidate variants. Additional studies associating variation at these loci with change in gene expression highlighted Tropomyosin 1 (TPM1) among our top-ranked candidate genes. CRISPR/Cas9-mediated TPM1 knockout in human induced pluripotent stem cells (iPSCs) enhanced hematopoietic progenitor development, increasing total megakaryocyte and erythroid cell yields. CONCLUSIONS: Our findings may help explain human genetic associations and identify a novel genetic strategy to enhance in vitro hematopoiesis. A similar trait-specific gene prioritization strategy could be employed to help streamline functional validation experiments for virtually any human trait.

Ultrasound-Guided Talonavicular Arthrocentesis.

BACKGROUND: Joint arthrocentesis is a commonly performed procedure by the emergency physician (EP). Point of care ultrasound (POCUS) has demonstrated promise in identifying joint effusions and guiding arthrocentesis procedures. EP-performed talonavicular joint arthrocentesis has not been previously described in the literature. We present a case in which an isolated talonavicular joint effusion was identified and then subsequently aspirated using POCUS. CASE REPORT: A 65-year-old man presented with atraumatic right ankle pain. On arrival, he was noted to have diffuse warmth and edema around the ankle and midfoot. POCUS was performed to evaluate for an ankle joint effusion, which was not present. The ultrasound was then moved distally, where a talonavicular joint effusion was noted. Inflammatory markers were found to be elevated. A magnetic resonance imaging scan revealed an isolated talonavicular joint effusion without additional acute findings. POCUS was then used to perform an arthrocentesis, which revealed monosodium urate crystals consistent with an initial episode of gouty arthritis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: POCUS provides the EP with an efficient tool to diagnose joint effusions and guide arthrocentesis procedures. The foot is composed of several small joints where ultrasound can be particularly helpful. Similar to the ankle joint, these joints can be afflicted with pyogenic infections and crystalline arthropathies. To our knowledge, we present the first report of EP-performed talonavicular arthrocentesis guided by POCUS. The approach to this joint and technique for arthrocentesis are presented.

FLI1 level during megakaryopoiesis affects thrombopoiesis and platelet biology.

Friend leukemia virus integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is among genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a patient with PTSx and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1+/-). PTSx and FLI1+/- iMegs replicate many of the described megakaryocyte/platelet features, including a decrease in iMeg yield and fewer platelets released per iMeg. Platelets released in vivo from infusion of these iMegs had poor half-lives and functionality. We noted that the closely linked E26 transformation-specific proto-oncogene 1 (ETS1) is overexpressed in these FLI1-deficient iMegs, suggesting FLI1 negatively regulates ETS1 in megakaryopoiesis. Finally, we examined whether FLI1 overexpression would affect megakaryopoiesis and thrombopoiesis. We found increased yield of noninjured, in vitro iMeg yield and increased in vivo yield, half-life, and functionality of released platelets. These studies confirm FLI1 heterozygosity results in pleiotropic defects similar to those noted with other critical megakaryocyte-specific TFs; however, unlike those TFs, FLI1 overexpression improved yield and functionality.

Can Ultrasound Identify Traumatic Knee Arthrotomy in a Cadaveric Model?

BACKGROUND: Traumatic arthrotomy of the knee (TAK) involves the violation of the knee capsule. TAK differs from simple lacerations because it requires operative management to prevent resultant septic arthritis. The diagnostic test of choice in the emergency department is the saline load test (SLT). SLT sensitivity ranges from 34% to 99%, depending on volume used. Computed tomography (CT) is a possible alternative, using intra-articular air as a diagnostic marker. Ultrasound can identify air in various tissues, given its highly echogenic nature. OBJECTIVE: We sought to determine the sensitivity and specificity of ultrasound for detecting intra-articular air in cadaveric knee joints. METHODS: Soft embalmed cadavers were utilized. The knees were block randomized to having 1 mL of air injected into the joint or sham skin injection. Two blinded, expert operators scanned the knees with a high-frequency linear transducer. The sensitivity and specificity were calculated. RESULTS: Twenty knees were included. Knees that had any prior dissection were excluded from analysis. Ten knees were randomized for air injection. The pooled sensitivity was 0.65 (95% confidence interval [CI] 0.41-0.85) with a specificity of 0.75 (95% CI 0.48-0.93). Mean time taken was 143 s. CONCLUSIONS: Ultrasound may have utility in evaluation of TAK. There were limitations. Some knees had effusions with echogenic material present, which could have led to false-positive results. It is also unknown how much air is typical of TAK. One milliliter was used based on previous work with CT. The use of ultrasound for diagnosis of TAK warrants further study.

Utility and limitations of exome sequencing in the molecular diagnosis of pediatric inherited platelet disorders.

Inherited platelet disorders (IPD) are a heterogeneous group of rare disorders that affect platelet number and function and often predispose to other significant medical complications. In spite of the identification of over 50 IPD disease-associated genes, a molecular diagnosis is only identified in a minority (10%) of affected patients without a clinically suspected etiology. We studied a cohort of 21 pediatric patients with suspected IPDs by exome sequencing (ES) to: (1) examine the performance of the exome test for IPD genes, (2) determine if this exome-wide diagnostic test provided a higher diagnostic yield than has been previously reported, (3) to evaluate the frequency of variants of uncertain significance identified, and (4) to identify candidate variants for functional evaluation in patients with an uncertain or negative diagnosis. We established a high priority gene list of 53 genes, evaluated exome capture kit performance, and determined the coverage for these genes and disease-related variants. We identified likely disease causing variants in 5 of the 21 probands (23.8%) and variants of uncertain significance in 52% of patients studied. In conclusion, ES has the potential to molecularly diagnose causes of IPD, and to identify candidate genes for functional evaluation. Robust exome sequencing also requires that coverage of genes known to be associated with clinical findings of interest need to be carefully examined and supplemented if necessary. Clinicians who undertake ES should understand the limitations of the test and the full significance of results that may be returned.

Point-of-Care Ultrasound Identifies Urinoma Complicating Simple Renal Colic: A Case Series and Literature Review.

BACKGROUND: Renal colic is a frequently encountered diagnosis among emergency department patients. Point-of-care (POC) ultrasound has taken on an increasingly important role in the diagnostic strategy of this disease, as it has been shown to be an effective modality for diagnosis and for guiding management. The primary pathology that the emergency physician will evaluate for in cases of suspected renal colic is hydronephrosis, which is a dilatation of the renal pelvis and calyces resulting from a distal obstruction such as a ureteral stone. However, other significant findings can be seen, one of which is the extravasation of urine around the kidney secondary to a forniceal, or calyceal, rupture. CASE SERIES: We present three cases of unanticipated perinephric fluid collections identified initially on POC ultrasound in cases of suspected simple renal colic. Concomitant hydronephrosis was also seen in each of these cases. Why Should an Emergency Physician Be Aware of This? While the utilization of POC ultrasound in cases of suspected renal colic increases, we should be prepared to encounter and identify perinephric fluid collections in our evaluations. Although the ideal management of these cases is not completely defined from the current literature, we benefit from knowing how to identify these on POC ultrasound, understanding the underlying pathophysiology, and appreciating the possibility of complications that may arise.

Never say never: Identification of acute pulmonary embolism on non-contrast computed tomography imaging.

Acute undifferentiated illness remains a critical challenge for the emergency physician. The diagnostic evaluation and treatment decisions on such severely ill patients often needs to be made in an expedited fashion. Situations occur wherein the ideal or recommended workup is not always feasible due to time or patient specific factors. We present two cases of patients with undifferentiated acute illness who had undergone non-contrast CT (computed tomography) scanning and subsequently had central pulmonary embolism identified upon careful review of their CT studies.

A Necrotizing Fasciitis Fake Out on Point-of-Care Ultrasound-Watch the Shadow.

BACKGROUND: Point-of-care ultrasound has an increasing role in characterizing soft-tissue infections and has been described previously in the evaluation of necrotizing fasciitis (NF). The identification of air within the soft tissues can be very suggestive of NF in the correct clinical context. CASE REPORT: A 78-year-old male presented to the emergency department with extensive lower-extremity redness and edema. A point-of-care ultrasound revealed hyperechoic areas within the soft tissues consistent with air, and the patient was taken to surgery and found to have NF. A 60-year-old female presented to the emergency department with physical examination findings consistent with severe cellulitis and associated sepsis. A point-of-care ultrasound revealed hyperechoic areas within the soft tissue that were very similar to the prior case. An emergent surgical consultation was placed due to concern for soft-tissue air and NF. However, these hyperechoic areas were found to be subcutaneous calcifications on subsequent imaging. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Air within the soft tissue is easy to identify on point-of-care ultrasound and can expedite surgical evaluation in cases of suspected NF. Calcifications can mimic the appearance of air on ultrasound and the distinction between these objects can often be made based on the echotexture of the posterior acoustic shadow. Attention to the posterior acoustic shadow can facilitate correct identification of various structures and pathologies in a variety of clinical settings.

Ultrasound measurement of inferior vena cava collapse predicts propofol-induced hypotension.

STUDY OBJECTIVES: Hypotension is a common side effect of propofol, but there are no reliable methods to determine which patients are at risk for significant propofol-induced hypotension (PIH). Ultrasound has been used to estimate volume status by visualization of inferior vena cava (IVC) collapse. This study explores whether IVC assessment by ultrasound can assist in predicting which patients may experience significant hypotension. METHODS: This was a prospective observational study conducted in the operating suite of an urban community hospital. A convenience sample of consenting adults planned to receive propofol for induction of anesthesia during scheduled surgical procedures were enrolled. Bedside ultrasound was used to measure maximum (IVCmax) and minimum (IVCmin) IVC diameters. IVC-CI was calculated as [(IVCmax-IVCmin)/IVCmax × 100%]. The primary outcome was significant hypotension defined as systolic blood pressure (BP) below 90mmHg and/or administration of a vasopressor to increase BP during surgery. RESULTS: The study sample comprised 40 patients who met inclusion criteria. Mean age was 55years, (95%CI, 49-60) with 53% female. 55% of patients had significant hypotension after propofol administration. 76% of patients with IVC-CI≥50% had significant hypotension compared to 39% with IVC-CI<50%, P=.02. IVC-CI≥50% had a specificity of 77.27% (95%CI, 64.29%-90.26%) and sensitivity of 66.67% (95%CI, 52.06%-81.28%) in predicting PIH. The odds ratio for PIH in patients with IVC-CI≥50% was 6.9 (95%CI, 1.7-27.5). CONCLUSION: Patients with IVC-CI≥50% were more likely to develop significant hypotension from propofol. IVC ultrasound may be a useful tool to predict which patients are at increased risk for PIH.