Diagnostic accuracy of prehospital lung ultrasound for acute decompensated heart failure: A systematic review and Meta-analysis.

BACKGROUND: Lung ultrasound (LUS) reduces time to diagnosis and treatment of acute decompensated heart failure (ADHF) in emergency department (ED) patients with undifferentiated dyspnea. We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of LUS for ADHF in the prehospital setting. METHODS: We performed a keyword search of multiple databases from inception through June 1, 2023. Included studies were those enrolling prehospital patients with undifferentiated dyspnea or suspected ADHF, and specifically diagnostic studies comparing prehospital LUS to a gold standard and intervention studies with a non-US comparator group. Title and abstract screening, full text review, risk of bias (ROB) assessments, and data extraction were performed by multiple authors. and adjudicated. The primary outcome was pooled sensitivity, specificity, and diagnostic likelihood ratios (LR) for prehospital LUS. A test-treatment threshold of 0.7 was applied based on prior ADHF literature in the ED. Intervention outcomes included mortality, mechanical ventilation, and time to HF specific treatment. RESULTS: Eight diagnostic studies (n = 691) and two intervention studies (n = 70) met inclusion criteria. No diagnostic studies were low-ROB. Both intervention studies were critical-ROB, and not pooled. Pooled sensitivity and specificity of prehospital LUS for ADHF were 86.7% (95%CI:70.8%-94.6%) and 87.5% (78.2%-93.2%), respectively, with similar performance by physician vs. paramedic LUS and number of lung zones evaluated. Pooled LR+ and LR- were 7.27 (95% CI: 3.69-13.10) and 0.17 (95% CI: 0.06-0.34), respectively. Area under the summary receiver operating characteristic curve was 0.922. At the observed 42.4% ADHF prevalence (pre-test probability), positive pre-hospital LUS exceeded the 70% threshold to initiate treatment (post-test probability 84%, 80-88%). CONCLUSIONS: LUS had similar diagnostic test characteristics for ADHF diagnosis in the prehospital setting as in the ED. A positive prehospital LUS may be sufficient to initiate early ADHF treatment based on published test-treatment thresholds. More studies are needed to determine the clinical impact of prehospital LUS.

Functional outcomes in MRI-guided laser interstitial therapy for temporal lobe epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The use of MRI-guided laser interstitial thermal therapy (MRgLITT) has emerged as a promising treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). Although the minimally invasive approach holds promise as an effective treatment for achieving seizure freedom, a comprehensive review of its impact on functional outcomes is still warranted. To address this need, this review aims to summarize data pertaining to the functional and neurocognitive outcomes following MRgLITT for TLE. METHODS: Four primary electronic databases were screened following PRISMA guidelines by two independent reviewers. All functional data related to cognitive, behavioral, and emotional outcomes were gathered and analyzed as well as the neuropsychological tests issued to assess pre- and postoperative outcomes. The functional outcomes assessed were grouped into the 5 most common categories: verbal cognition, visual cognition, cognitive emotion, visual deficits, and other higher-order cognitive functioning. RESULTS: A total of 4184 studies were screened and ultimately 408 patients from 14 studies were included for analysis. Changes in functional areas were assessed by comparing pre- and postoperative scores across a comprehensive set of 31 different functional and cognitive assessments, and were tabulated as the percentage of patients whose status improved, declined, or was maintained, where possible. In verbal (n = 112) and visual (n = 42) cognition, the rates of patients experiencing a decline were 20.4% and 13.5%, respectively, and the rates of improvement were 24.9% and 16.7%, respectively. Other functional outcomes assessed, including cognitive emotion (n = 150), visual deficits (n = 325), and higher-order cognitive processes like attention/processing (n = 19), motor cognition (n = 18), and general executive function (n = 4), exhibited varying rates of decline, ranging from 10.5% to 25%. CONCLUSIONS: MRgLITT is an effective and minimally invasive surgical alternative treatment for TLE, but there is an observable impact on patient functioning and cognitive status. This review demonstrates the need for standardized methods that can accurately capture and quantify the associated risk of MRgLITT to optimize its effect on patient quality of life moving forward.

Persistent tailoring of MSC activation through genetic priming.

Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce expression of pro-inflammatory effectors that can potentiate immunogenicity. Here, we describe a 'genetic priming' method that can both selectively and sustainably boost MSC potency via the controlled expression of the inflammatory-stimulus-responsive transcription factor IRF1 (interferon response factor 1). MSCs engineered to hyper-express IRF1 recapitulate many core responses that are accessed by biochemical priming using the proinflammatory cytokine interferon-γ (IFNγ). This includes the upregulation of anti-inflammatory effector molecules and the potentiation of MSC capacities to suppress T cell activation. However, we show that IRF1-mediated genetic priming is much more persistent than biochemical priming and can circumvent IFNγ-dependent expression of immunogenic MHC class II molecules. Together, the ability to sustainably activate and selectively tailor MSC priming responses creates the possibility of programming MSC activation more comprehensively for therapeutic applications.

Emergency department management of patients with right heart failure.

Right heart failure (RHF) can result from many cardiac, pulmonary, and systemic pathologies. Common causes of RHF include pulmonary embolism, left heart failure, congenital heart disease, chronic lung disease, acute myocardial infarction, infiltrative disease, infectious disease, and valvular abnormalities. Acute and chronic RHF confer a high risk for morbidity and mortality in the acute care setting, and interventions commonly used in emergency care can prompt acute decompensation if the RHF is not recognized. The severity of presentation may range from compensated clinically silent cardiovascular dysfunction to venous congestion, multiorgan failure, and circulatory collapse. This review describes the pathophysiology of right heart failure and offers an evidence-based approach to the diagnosis, management, and disposition of both acute and chronic RHF.

Brain abscesses following carotid blowout syndrome: a case report.

We report a case of intracranial abscesses development in a patient with head and neck cancer after emergent treatment of carotid blowout syndrome with coil embolization. Our patient is a 60-year-old male who presented with hemoptysis and hematemesis, which raised concerns for impending carotid blowout syndrome. Endovascular occlusion was successfully achieved, and the patient was discharged in stable condition. Ten days later, the patient reported headaches and right facial pain, and magnetic resonance imaging revealed multiple intracranial abscesses. Broad-spectrum intravenous antibiotics were administered, leading to a variable response with some abscesses decreasing in size and others increasing. Seven weeks from discharge, the patient had no neurological deficits, and all abscesses had decreased in size.

Ischemic Stroke in a Seven-Year-Old Female With Down Syndrome and Newly Discovered Moyamoya Syndrome.

Moyamoya represents a rare, progressive cerebrovascular disease, characterized by a gradual stenosis of the intracranial internal carotid arteries, thereby increasing the risk of stroke. Down syndrome is known to be a predisposing factor for Moyamoya syndrome. This review discusses a distinctive case of a seven-year-old female with Down syndrome who manifested with Moyamoya syndrome, evident from acute stroke-like symptoms.

Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.

Engineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR-Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors. We used these components to construct potent and compact multipartite transactivation modules (MSN, NMS and eN3x9) and to build the CRISPR-dCas9 recruited enhanced activation module (CRISPR-DREAM) platform. We found that CRISPR-DREAM was specific and robust across mammalian cell types, and efficiently stimulated transcription from diverse regulatory loci. We also showed that MSN and NMS were portable across Type I, II and V CRISPR systems, transcription activator-like effectors and zinc finger proteins. Further, as proofs of concept, we used dCas9-NMS to efficiently reprogram human fibroblasts into induced pluripotent stem cells and demonstrated that mechanosensitive transcription factor TADs are efficacious and well tolerated in therapeutically important primary human cell types. Finally, we leveraged the compact and potent features of these engineered TADs to build dual and all-in-one CRISPRa AAV systems. Altogether, these compact human TADs, fusion modules and delivery architectures should be valuable for synthetic transcriptional control in biomedical applications.

Examining the effect of high-frequency information on the classification of conversationally produced English fricativesa).

This study examines the role of frequencies above 8 kHz in the classification of conversational speech fricatives [f, v, θ, ð, s, z, ʃ, ʒ, h] in random forest modeling. Prior research has mostly focused on spectral measures for fricative categorization using frequency information below 8 kHz. The contribution of higher frequencies has received only limited attention, especially for non-laboratory speech. In the present study, we use a corpus of sociolinguistic interview recordings from Western Canadian English sampled at 44.1 and 16 kHz. For both sampling rates, we analyze spectral measures obtained using Fourier analysis and the multitaper method, and we also compare models without and with amplitudinal measures. Results show that while frequency information above 8 kHz does not improve classification accuracy in random forest analyses, inclusion of such frequencies can affect the relative importance of specific measures. This includes a decreased contribution of center of gravity and an increased contribution of spectral standard deviation for the higher sampling rate. We also find no major differences in classification accuracy between Fourier and multitaper measures. The inclusion of power measures improves model accuracy but does not change the overall importance of spectral measures.

Ictogenesis proceeds through discrete phases in hippocampal CA1 seizures in mice.

Epilepsy is characterized by spontaneous non-provoked seizures, yet the mechanisms that trigger a seizure and allow its evolution remain underexplored. To dissect out phases of ictogenesis, we evoked hypersynchronous activity with optogenetic stimulation. Focal optogenetic activation of putative excitatory neurons in the mouse hippocampal CA1 reliably evoked convulsive seizures in awake mice. A time-vs-time pulsogram plot characterized the evolution of the EEG pulse response from a light evoked response to induced seizure activity. Our results depict ictogenesis as a stepwise process comprised of three distinctive phases demarcated by two transition points. The induction phase undergoes the first transition to reverberant phase activity, followed by the second transition into the paroxysmal phase or a seizure. Non-seizure responses are confined to either induction or reverberant phases. The pulsogram was then constructed in seizures recorded from a murine model of temporal lobe epilepsy and it depicted a similar reverberance preceding spontaneous seizures. The discovery of these distinct phases of ictogenesis may offer means to abort a seizure before it develops.

Novel banana lectin CAR-T cells to target pancreatic tumors and tumor-associated stroma.

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal adenocarcinoma (PDAC), intractable tumors with aberrant glycosylation and characterized by desmoplastic stroma largely contributed by pancreatic stellate cells (PSCs). METHODS: We transduced human T cells with a second-generation retroviral construct expressing the H84T BanLec chimeric receptor, measured T-cell expansion, characterized T-cell phenotype, and tested their efficacy against PDAC tumor cells lines by flow cytometry quantification. In three-dimensional (3D) spheroid models, we measured H84T CAR T-cell disruption of PSC architecture, and T-cell infiltration by live imaging. We tested the activity of H84T CAR T cells against tumor xenografts derived from three PDAC cell lines. Antitumor activity was quantified by caliper measurement and bioluminescence signal and used anti-human vimentin to measure residual PSCs. RESULTS: H84T BanLec CAR was successfully transduced and expressed by T cells which had robust expansion and retained central memory phenotype in both CD4 and CD8 compartments. H84T CAR T cells targeted and eliminated PDAC tumor cell lines. They also disrupted PSC architecture in 3D models in vitro and reduced total tumor and stroma cells in mixed co-cultures. H84T CAR T cells exhibited improved T-cell infiltration in multicellular spheroids and had potent antitumor effects in the xenograft models. We observed no adverse effects against normal tissues. CONCLUSIONS: T cells expressing H84T CAR target malignant cells and their stroma in PDAC tumor models. The incorporation of glycan-targeting lectins within CARs thus extends their activity to include both malignant cells and their supporting stromal cells, disrupting the TME that otherwise diminishes the activity of cellular therapies against solid tumors.

Temporal and spectral characteristics of conversational versus read fricatives in American English.

The present study compares the production of fricatives in conversational versus read speech in American English. The goal is to examine which parameters contribute to the identification of fricatives across the two speech styles. The study surveys over 162 000 fricative tokens from the Buckeye Corpus [Pitt, Johnson, Hume, Kiesling, and Raymond (2005). Speech Commun. 45, 89-95] and the TIMIT Corpus [Zue and Seneff (1996). Recent Research towards Advanced Man-Machine Interface through Spoken Language (Elsevier, Amsterdam, the Netherlands), pp. 515-525]. A total of 18 different temporal and spectral measures are tested, including segment duration, preceding and following phone duration, spectral moments (at onset, midpoint, and/or offset), spectral peak frequency, etc. Results show that segment duration and midpoint spectral moments make the most prominent contribution to the categorization of fricatives for both speech styles. Spectral measures are more important for conversational speech, whereas duration plays a greater role for read speech. At the same time, the magnitude of the differences across speech styles is often low and many of the observed effects may be attributable to methodological differences across the corpora. Results may indicate that reduction of fricatives in conversational speech is more limited compared to the reduction of other types of speech sounds, such as plosives.

Diabetic ketoacidosis after the treatment of anaphylaxis.

Summary: Anaphylaxis is a rapidly progressive potentially lethal condition, and epinephrine is the most crucial medication in its treatment. In this study, we present a case of diabetic ketoacidosis in a young woman that was precipitated by the administration of epinephrine to treat anaphylaxis. This patient had diabetes mellitus and poor glycemic control and developed ketoacidosis despite having evidence of ongoing endogenous insulin production and having been treated with exogenous long-acting insulin less than 24 h prior to the event. This is a rare, serious, adverse side effect of life-saving medication. This report demonstrates that the risk of diabetic ketoacidosis should be considered when administering epinephrine to patients with diabetes, even in the absence of complete insulin deficiency. Learning points: Epinephrine directly suppresses insulin secretion, stimulates lipolysis, and causes ketone body generation. High-dose catecholamine administration can cause unexpected diabetic ketoacidosis in patients with risk factors. Early administration of insulin may not protect patients from developing ketoacidosis in the setting of high-dose catecholamine administration.

Acute large-vessel occlusion masquerading as traumatic injury.

A patient presented to an urban level 1 trauma center/accredited thrombectomy-capable stroke center for evaluation of suspected traumatic injury and was quickly determined to have symptoms suspicious for acute stroke that included dense hemiparesis with preserved mental status. He received a thrombectomy with an eventual return to neurologic baseline and discharge to acute inpatient rehabilitation 14 days after presentation.

Success of implementation of a systemwide point-of-care ultrasound privileging program for emergency medicine faculty.

Objectives: Point-of-care ultrasound (POCUS) is widely used in the emergency department (ED). Not all practicing emergency physicians received POCUS training during residency, leaving a training gap that is reflected in POCUS privileging. The purpose of this study was to evaluate the success of meeting privileging criteria as well as associated factors, following implementation of a basic POCUS training and privileging program within a large emergency medicine department. Methods: We implemented a POCUS training and privileging program, based on national guidelines, for faculty physicians who worked at one of the following EDs staffed by the same emergency medicine department: a pediatric tertiary site, two tertiary academic sites, and seven community sites. POCUS examinations included aorta, cardiac, first-trimester obstetrics (OB), and extended focused assessment with sonography in trauma. Pediatric emergency medicine faculty were taught soft tissue and thoracic US instead of aorta and OB. Completion of the program required 16 h of didactics, ≥25 quality-assured US examinations by examination type, and passing a series of knowledge-based examinations. Descriptive statistics were calculated. Associations between physician characteristics and successfully becoming privileged in POCUS were modeled using Firth's logistic regression. Results: A total of 176 faculty physicians were eligible. A total of 145 (82.4%) achieved basic POCUS privileging during the study period. Different pathways were used including 86 (48.9%) practice-based, nine (5.1%) fellowship-based, and 82 (46.9%) residency-based. POCUS privileging was lower for those working in a community versus academic setting (odds ratio 0.3, 95% confidence interval 0.1-0.9). A greater number of scans completed prior to the privileging program was associated with greater success. Conclusions: Implementation of a POCUS training and privileging program can be successful in a large emergency medicine department that staffs hospitals in a large-scale health care system composed of both academic and community sites. Faculty physicians with at least some prior exposure to POCUS were more successful.

Approach to Abdominal Imaging in 2022.

Abdominal pain represents 5% to 7% of all emergency department presentations. Many patients require imaging for diagnosis, and choosing the appropriate imaging modality is a crucial decision point. Modern medicine offers a fantastic array of options including abdominal radiograph, computed tomography, MRI, and ultrasonography, but the plethora of alternatives can be paralyzing. This article introduces the commonly available modalities, discusses the advantages and disadvantages, and presents current recommendations for commonly diagnosed conditions.

Diagnostic accuracy of lung ultrasound for SARS-CoV-2: a retrospective cohort study.

BACKGROUND: As medical infrastructures are strained by SARS-CoV-2, rapid and accurate screening tools are essential. In portions of the world, reverse transcription polymerase chain reaction (RT-PCR) testing remains slow and in limited supply, and computed tomography is expensive, inefficient, and involves exposure to ionizing radiation. Multiple studies evaluating the efficiency of lung point-of-care ultrasound (POCUS) have been published recently, but include relatively small cohorts and often focus on characteristics associated with severe illness rather than screening efficacy. This study utilizes a retrospective cohort to evaluate the test characteristics (sensitivity, specificity, likelihood ratios, predictive values) of lung POCUS in the diagnosis of SARS-CoV-2, and to determine lung score cutoffs that maximize performance for use as a screening tool. RESULTS: Lung POCUS examinations had sensitivity 86%, specificity 71.6%, NPV 81.7%, and PPV 77.7%. The Lung Ultrasound Score had an area under the curve of 0.84 (95% CI 0.78, 0.90). When including only complete examinations visualizing 12 lung fields, lung POCUS had sensitivity 90.9% and specificity 75.6%, with NPV 87.2% and PPV 82.0% and an area under the curve of 0.89 (95% CI 0.83, 0.96). Lung POCUS was less accurate in patients with a history of interstitial lung disease, severe emphysema, and heart failure. CONCLUSIONS: When applied in the appropriate patient population, lung POCUS is an inexpensive and reliable tool for rapid screening and diagnosis of SARS-CoV-2 in symptomatic patients with influenza-like illness. Adoption of lung POCUS screening for SARS-CoV-2 may identify patients who do not require additional testing and reduce the need for RT-PCR testing in resource-limited environments and during surge periods.