Point-of-care ultrasound in geriatrics: a national survey of VA medical centers.

BACKGROUND: Point-of-care ultrasound (POCUS) can aid geriatricians in caring for complex, older patients. Currently, there is limited literature on POCUS use by geriatricians. We conducted a national survey to assess current POCUS use, training desired, and barriers among Geriatrics and Extended Care ("geriatric") clinics at Veterans Affairs Medical Centers (VAMCs). METHODS: We conducted a prospective observational study of all VAMCs between August 2019 and March 2020 using a web-based survey sent to all VAMC Chiefs of Staff and Chiefs of geriatric clinics. RESULTS: All Chiefs of Staff (n=130) completed the survey (100% response rate). Chiefs of geriatric clinics ("chiefs") at 76 VAMCs were surveyed and 52 completed the survey (68% response rate). Geriatric clinics were located throughout the United States, mostly at high-complexity, urban VAMCs. Only 15% of chiefs responded that there was some POCUS usage in their geriatric clinic, but more than 60% of chiefs would support the implementation of POCUS use. The most common POCUS applications used in geriatric clinics were the evaluation of the bladder and urinary obstruction. Barriers to POCUS use included a lack of trained providers (56%), ultrasound equipment (50%), and funding for training (35%). Additionally, chiefs reported time utilization, clinical indications, and low patient census as barriers. CONCLUSIONS: POCUS has several potential applications for clinicians caring for geriatric patients. Though only 15% of geriatric clinics at VAMCs currently use POCUS, most geriatric chiefs would support implementing POCUS use as a diagnostic tool. The greatest barriers to POCUS implementation in geriatric clinics were a lack of training and ultrasound equipment. Addressing these barriers systematically can facilitate implementation of POCUS use into practice and permit assessment of the impact of POCUS on geriatric care in the future.

Design and evaluation of the I-SCAN faculty POCUS program.

BACKGROUND: Point-of-care ultrasound (POCUS) is becoming widely adopted with increasing accessibility of courses. Little is known about the optimal design of the introductory course or longitudinal training programs targeting hospitalists that are critical to success. METHODS: Hospitalists at four academic sites participated in a two-day introductory course and a longitudinal phase comprising clinical POCUS practice, clip uploading with online feedback, hands-on teaching, and monthly ultrasound conferences. Assessments were performed immediately before and after the two-day course and after 1 year. RESULTS: Knowledge increased from baseline to post two-day course (median score 58 and 85%, respectively, p < 0.001) and decreased slightly at 1 year (median score 81%, p = 0.012). After the two-day introductory course, the median score for hands-on image acquisition skills, the principal metric of participant success, was 75%. After 1 year, scores were similar (median score 74%). Confidence increased from baseline to post two-day course (1.5 to 3.1 on a 4 point Likert scale from Not at all confident (1) to Very confident (4), p < 0.001), and remained unchanged after 1 year (2.73). Course elements correlating with a passing score on the final hands-on test included number of clip uploads (r = 0.85, p,0.001), attendance at hands-on sessions (r = 0.7, p = 0.001), and attendance at monthly conferences (r = 0.50, p = 0.03). CONCLUSIONS: The I-ScaN POCUS training program increased hospitalist knowledge, skill and confidence with maintained skill and confidence after 1 year. Uploading clips and attending hands-on teaching sessions were most correlative with participant success.

Assessing Extravascular Lung Water With Ultrasound: A Tool to Individualize Fluid Management?

Aggressive fluid resuscitation has become standard of care for hypotensive patients with sepsis. However, sepsis is a syndrome that occurs in patients with diverse underlying physiology and a one-size-fits-all approach to fluid administration seems misguided. To individualize fluid management, several methods to assess fluid responsiveness have been validated, but even in fluid responsive patients, fluid administration may still be harmful and lead to pulmonary edema. Hence, to individualize fluid management, in addition to fluid responsiveness, fluid tolerance needs to be assessed. This article examines whether lung ultrasound can be useful to detect excess extravascular lung water (EVLW) and thus assess fluid tolerance. The physiology of EVLW and the principles of lung ultrasound are briefly described. Articles examining the correlation between EVLW and lung ultrasound findings in various clinical settings are carefully reviewed. Overall, lung ultrasound has been found to be an excellent tool to detect EVLW, but large outcome studies investigating lung ultrasound-guided fluid management are still lacking.

Feasibility of tele-guided patient-administered lung ultrasound in heart failure.

BACKGROUND: Readmission rates for heart failure remain high, and affordable technology for early detection of heart failure decompensation in the home environment is needed. Lung ultrasound has been shown to be a sensitive tool to detect pulmonary congestion due to heart failure, and monitoring patients in their home environment with lung ultrasound could help to prevent hospital admissions. The aim of this project was to investigate whether patient-performed tele-guided ultrasound in the home environment using an ultraportable device is feasible.Affiliations: Journal instruction requires a country for affiliations; however, these are missing in affiliations [1, 2]. Please verify if the provided country are correct and amend if necessary.Correct METHODS: Stable ambulatory patients with heart failure received a handheld ultrasound probe connected to a smart phone or tablet. Instructions for setup were given in person during a clinic visit or over the phone. During each ultrasound session, patients obtained six ultrasound clips from the anterior and lateral chest with verbal and visual tele-guidance from an ultrasound trained clinician. Patients also reported their weight and degree of dyspnea, graded on a 5-point scale. Two independent reviewers graded the ultrasound clips based on the visibility of the pleural line and A or B lines. RESULTS: Eight stable heart failure patients each performed 10-12 lung ultrasound examinations at home under remote guidance within a 1-month period. There were no major technical difficulties. A total of 89 ultrasound sessions resulted in 534 clips of which 88% (reviewer 1) and 84% (reviewer 2) were interpretable. 91% of ultrasound sessions produced interpretable clips bilaterally from the lateral chest area, which is most sensitive for the detection of pulmonary congestion. The average time to complete an ultrasound session was 5 min with even shorter recording times for the last session. All patients were clinically stable during the study period and no false positive B-lines were observed. CONCLUSIONS: In this feasibility study, patients were able to produce interpretable lung ultrasound exams in more than 90% of remotely supervised sessions in their home environment. Larger studies are needed to determine whether remotely guided lung ultrasound could be useful to detect heart failure decompensation early in the home environment.

Current Use and Barriers to Point-of-Care Ultrasound in Primary Care: A National Survey of VA Medical Centers.

BACKGROUND: More primary care providers (PCPs) have begun to embrace the use of point-of-care ultrasound (POCUS), but little is known about how PCPs are currently using POCUS and what barriers exist. In this prospective study, the largest systematic survey of POCUS use among PCPs, we assessed the current use, barriers to use, program management, and training needs for POCUS in primary care. METHODS: We conducted a prospective observational study of all VA Medical Centers (VAMCs) between June 2019 and March 2020 using a web-based survey sent to all VAMC Chiefs of Staff and Chiefs of primary care clinics (PCCs). RESULTS: Chiefs of PCCs at 105 VAMCs completed the survey (82% response rate). Only 13% of PCCs currently use POCUS, and the most common applications used were bladder and musculoskeletal ultrasound. Desire for POCUS training exceeded current use, but lack of trained providers (78%), ultrasound equipment (66%), and funding for training (41%) were common barriers. Program infrastructure to support POCUS use was uncommon, and only 9% of VAMCs had local policies related to POCUS. Most PCC chiefs (64%) would support POCUS training. CONCLUSIONS: Current use of POCUS in primary care is low despite the recent growth of POCUS training in Internal Medicine residency programs. Investment in POCUS training and program infrastructure is needed to expand POCUS use in primary care and ensure adequate supervision of trainees.

Expressed cell-penetrating peptides can induce a bystander effect, but passage through the secretory pathway reduces protein transduction activity.

Despite advances in vector technology, inefficient gene transfer still limits clinical efficacy of cancer gene therapy. Cell-penetrating peptides (CPPs), such as the basic domain of the transactivator of transcription (Tat) protein of HIV-1, are internalized by intact cells and have been used to deliver purified recombinant proteins. A combination of gene therapy with protein transduction technology could induce a strong bystander effect and represent a platform to deliver proteins to target cells. However, whether expressed CPP can facilitate intercellular trafficking, i.e., a bystander effect, is controversial. Our data suggest that expressed fusion proteins that contain the basic domain of Tat do not induce a detectable bystander effect. However, Tat-fusion proteins that also contain a secretory signal peptide (SP) can induce a bystander effect in vitro, although the in vivo effect is small. Surprisingly, despite the presence of a SP, the bystander effect does not seem to be related to secretion of the fusion protein. In fact, Tat-fusion proteins are secreted very inefficiently, and protein transduction seems largely mediated by fusion proteins that are released by cell lysis. Modification of Tat can improve secretion efficacy and prevent cleavage by the endoprotease furin, but passage through the secretory pathway is associated with reduced transduction activity of Tat-fusion proteins.

Measurement of Cardiac Output by Point-of-Care Transthoracic Echocardiography.

Traditionally measured with invasive methods or specialized equipment, stroke volume and cardiac output can be determined reliably with transthoracic echocardiography. This video guides the viewer in a step-by-step fashion through the technical aspects of Doppler echocardiographic assessment of cardiac output.

Design and comparison of a hybrid to a traditional in-person point-of-care ultrasound course.

BACKGROUND: Traditional introductory point-of-care ultrasound (POCUS) courses are resource intensive, typically requiring 2-3 days at a remote site, consisting of lectures and hands-on components. Social distancing requirements resulting from the COVID-19 pandemic led us to create a novel hybrid course curriculum consisting of virtual and in-person components. METHODS: Faculty, chief residents, fellows and advanced practice providers (APPs) in the Department of Medicine were invited to participate in the hybrid curriculum. The course structure included 4 modules of recorded lectures, quizzes, online image interpretation sessions, online case discussions, and hands-on sessions at the bedside of course participant's patients. The components of the course were delivered over approximately 8 months. Those participants who completed a minimum of 3 modules over the year were invited for final assessments. Results from the hybrid curriculum cohort were compared to the year-end data from a prior traditional in-person cohort. RESULTS: Participant knowledge scores were not different between traditional (n = 19) and hybrid (n = 24) groups (81% and 84%, respectively, P = 0.9). There was no change in POCUS skills as measured by the hands-on test from both groups at end-of-course (76% and 76%, respectively, P = 0.93). Confidence ratings were similar across groups from 2.73 traditional to 3.0 hybrid (out of possible 4, P = 0.46). Participants rated the course highly, with an average overall rating of 4.6 out 5. CONCLUSIONS: A hybrid virtual and in-person POCUS course was highly rated and as successful as a traditional course in improving learner knowledge, hands-on skill and confidence at 8 months after course initiation. These results support expanding virtual elements of POCUS educational curricula.

Development of a multisystem point of care ultrasound skills assessment checklist.

BACKGROUND: Many institutions are training clinicians in point-of-care ultrasound (POCUS), but few POCUS skills checklists have been developed and validated. We developed a consensus-based multispecialty POCUS skills checklist with anchoring references for basic cardiac, lung, abdominal, and vascular ultrasound, and peripheral intravenous line (PIV) insertion. METHODS: A POCUS expert panel of 14 physicians specializing in emergency, critical care, and internal/hospital medicine participated in a modified-Delphi approach to develop a basic POCUS skills checklist by group consensus. Three rounds of voting were conducted, and consensus was defined by ≥ 80% agreement. Items achieving < 80% consensus were discussed and considered for up to two additional rounds of voting. RESULTS: Thirteen POCUS experts (93%) completed all three rounds of voting. Cardiac, lung, abdominal, and vascular ultrasound checklists included probe location and control, basic machine setup, image quality and optimization, and identification of anatomical structures. PIV insertion included additional items for needle tip tracking. During the first round of voting, 136 (82%) items achieved consensus, and after revision and revoting, an additional 21 items achieved consensus. A total of 153 (92%) items were included in the final checklist. CONCLUSIONS: We have developed a consensus-based, multispecialty POCUS checklist to evaluate skills in image acquisition and anatomy identification for basic cardiac, lung, abdominal, and vascular ultrasound, and PIV insertion.

Current use, training, and barriers in point-of-care ultrasound in hospital medicine: A national survey of VA hospitals.

BACKGROUND: Point-of-care ultrasound (POCUS) can reduce procedural complications and improve the diagnostic accuracy of hospitalists. Currently, it is unknown how many practicing hospitalists use POCUS, which applications are used most often, and what barriers to POCUS use exist. OBJECTIVE: This study aimed to characterize current POCUS use, training needs, and barriers to use among hospital medicine groups (HMGs). DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study of all Veterans Affairs (VA) medical centers was conducted between August 2019 and March 2020 using a web-based survey sent to all chiefs of HMGs. These data were compared to a similar survey conducted in 2015. RESULT: Chiefs from 117 HMGs were surveyed, with a 90% response rate. There was ongoing POCUS use in 64% of HMGs. From 2015 to 2020, procedural POCUS use decreased by 19%, but diagnostic POCUS use increased for cardiac (8%), pulmonary (7%), and abdominal (8%) applications. The most common barrier to POCUS use was lack of training (89%), and only 34% of HMGs had access to POCUS training. Access to ultrasound equipment was the least common barrier (57%). The proportion of HMGs with ≥1 ultrasound machine increased from 29% to 71% from 2015 to 2020. An average of 3.6 ultrasound devices per HMG was available, and 45% were handheld devices. CONCLUSION: From 2015 to 2020, diagnostic POCUS use increased, while procedural use decreased among hospitalists in the VA system. Lack of POCUS training is currently the most common barrier to POCUS use among hospitalists.

Comparison of four handheld point-of-care ultrasound devices by expert users.

BACKGROUND: Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+™ by Butterfly Network Inc., Kosmos™ by EchoNous, Vscan Air™ by General Electric, and Lumify™ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes. RESULTS: Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Air™ was rated highest, followed by the Lumify™. For overall image quality, Lumify™ was rated highest, followed by Kosmos™. The Lumify™ device was rated highest for overall satisfaction, while the Vscan Air™ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes. CONCLUSIONS: In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumify™ highest for image quality and Vscan Air™ highest for ease of use. Overall satisfaction was highest with the Lumify™ device, while the most likely to be purchased as a pocket device was the Vscan Air™. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices.

Lung Ultrasound Imaging: A Primer for Echocardiographers.

Lung ultrasound (LUS) has gained considerable acceptance in emergency and critical care medicine but is yet to be fully implemented in cardiology. Standard imaging protocols for LUS in acute care settings have allowed the rapid and accurate diagnosis of dyspnea, respiratory failure, and shock. LUS is greatly additive to echocardiography and is superior to auscultation and chest radiography, particularly when the diagnosis of acute decompensated heart failure is in question. In this review, the authors describe LUS techniques, interpretation, and clinical applications, with the goal of informing cardiologists on the imaging modality. Additionally, the authors review LUS findings associated with various disease states most relevant to cardiac care. Although there is extensive literature on LUS in the acute care setting, there is a dearth of reviews directly focused for practicing cardiologists. Current evidence demonstrates that this modality is an important adjunct to echocardiography, providing valuable clinical information at the bedside.

Lower Airway Dysbiosis Affects Lung Cancer Progression.

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB-IV tumor-node-metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB-IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. SIGNIFICANCE: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis.See related commentary by Zitvogel and Kroemer, p. 224.This article is highlighted in the In This Issue feature, p. 211.

Angiopoietin-1 increases survival and reduces the development of lung edema induced by endotoxin administration in a murine model of acute lung injury.

OBJECTIVE: To evaluate the effect of angiopoietin-1, an angiogenic growth factor, on lung capillary leakage and survival in a murine model of acute lung injury. DESIGN: Laboratory investigation. SETTING: Research laboratory at New York University School of Medicine and Department of Veterans Affairs, NY Harbor Healthcare System. SUBJECTS: C57BL/6 mice weighing 18-20 g, susceptible to endotoxin-induced acute lung injury. INTERVENTIONS: Acute lung injury was induced in C57BL/6 mice by the intraperitoneal administration of endotoxin. The effects of angiopoietin-1, expressed from a nonreplicating E1a-deleted adenovirus containing the angiopoietin-1 complementary DNA (AdAng1), on survival and lung injury were evaluated. An E1a-deleted adenovirus that does not contain a transgene (Ad312) and phosphate-buffered saline were used as controls. MEASUREMENTS AND MAIN RESULTS: Angiopoietin-1 protein was detected by immunoblotting in the serum of mice that received an intraperitoneal injection of AdAng1 but not in mice that received the control virus Ad312. When compared with control groups, mice that received AdAng1 5 days before endotoxin administration had improved survival and significantly less protein leakage from the circulation into the lungs, as detected by quantitative spectrophotometric measurements of Evans blue dye. Furthermore, when compared with controls, histopathology and immunostaining of lungs against CD31 and smooth muscle actin suggested preservation of vascular integrity and decreased tissue damage in mice pretreated with AdAng1. When endotoxin administration preceded infection with AdAng1 by 3 hrs, no benefit was observed. CONCLUSIONS: These data show that adenoviral mediated expression of angiopoietin-1 can protect against the development of lung capillary protein leak and decrease the mortality induced by endotoxin. However, the timing of AdAng1 administration in relation to the onset of lung injury may be critical.

Therapeutic hypothermia after cardiac arrest in a patient with systemic sclerosis and Raynaud phenomenon.

Therapeutic hypothermia favorably impacts neurologic outcomes in patients after cardiopulmonary arrest, although the appropriate target temperature is less clear. Its safety profile in patients with systemic sclerosis (SSc) and Raynaud phenomenon (RP), who may be at increased risk for ischemic complications, has not been addressed in the literature, to our knowledge. Digital lesions are commonly seen in patients with SSc, and cold-induced myocardial ischemia has also been reported. We describe a case of a man with SSc, RP, and digital ulcers who underwent therapeutic hypothermia after cardiopulmonary arrest. He regained full neurologic function, and except for digital necrosis, no hypothermia-associated adverse events were observed. Other risk factors for ischemia, such as cocaine use, may have contributed to the development of the digital necrosis. However, clinicians should be aware of the risk for ischemic complications in patients with SSc and RP when considering the appropriate target temperature after cardiopulmonary arrest.

Intratumoral spread of wild-type adenovirus is limited after local injection of human xenograft tumors: virus persists and spreads systemically at late time points.

Oncolytic replicating adenoviruses are a promising new modality for the treatment of cancer. Despite the assumed biologic advantage of continued viral replication and spread from infected to uninfected cancer cells, early clinical trials demonstrate that the efficacy of current vectors is limited. In xenograft tumor models using immune-incompetent mice, wild-type adenovirus is also rarely able to eradicate established tumors. This suggests that innate immune mechanisms may clear the virus or that barriers within the tumor prevent viral spread. The aim of this study was to evaluate the kinetics of viral distribution and spread after intratumoral injection of virus in a human tumor xenograft model. After intratumoral injection of wild-type virus, high levels of titratable virus persisted within the xenograft tumors for at least 8 weeks. Virus distribution within the tumors as determined by immunohistochemistry was patchy, and virus-infected cells appeared to be flanked by tumor necrosis and connective tissue. The close proximity of virus-infected cells to the tumor-supporting structure, which is of murine origin, was clearly demonstrated using a DNA probe that specifically hybridizes to the B1 murine DNA repeat. Importantly, although virus was cleared from the circulation 6 hr after intratumoral injection, after 4 weeks systemic spread of virus was detected. In addition, vessels of infected tumors were surrounded by necrosis and an advancing rim of virus-infected tumor cells, suggesting reinfection of the xenograft tumor through the vasculature. These data suggest that human adenoviral spread within tumor xenografts is impaired by murine tumor-supporting structures. In addition, there is evidence for continued viral replication within the tumor, with subsequent systemic dissemination and reinfection of tumors via the tumor vasculature. Despite the limitations of immune-incompetent models, an understanding of the interactions between the virus and the tumor-bearing host is important in the design of effective therapies.

Late expression of p53 from a replicating adenovirus improves tumor cell killing and is more tumor cell specific than expression of the adenoviral death protein.

Gene transfer of p53 induces cell death in most cancer cells, and replication-defective adenoviral vectors expressing p53 are being evaluated in clinical trials. However, low transduction efficiency limits the efficacy of replication-defective vector systems for cancer therapy. The use of replication-competent vectors for gene delivery may have several advantages, holding the potential to multiply and spread the therapeutic agent after infection of only a few cells. However, expression of a transgene may adversely affect viral replication. We have constructed a replicating adenoviral vector (Adp53rc) that expresses high levels of p53 at a late time point in the viral life cycle and also contains a deletion of the adenoviral death protein (ADP). Adp53rc-infected cancer cells demonstrated high levels of p53 expression in parallel with the late expression pattern of the adenoviral fiber protein. p53 expression late in the viral life cycle did not impair effective virus propagation. Survival of several lung cancer cell lines was significantly diminished after infection with Adp53rc, compared with an identical p53-negative control virus. p53 expression also improved virus release and spread. Interestingly, p53 was more cytotoxic than the ADP in cancer cells but less cytotoxic than the ADP in normal cells. In conclusion, late expression of p53 from a replicating virus improves tumor cell killing and viral spread without impairing viral replication. In addition, in combination with a deletion of the ADP, specificity of tumor cell killing is improved.

A novel cell-penetrating peptide to facilitate intercellular transport of fused proteins.

Cell-based delivery of cell penetrating peptides (CPPs) could represent a new platform for intracellular peptide delivery to local tissues. Expressed CPPs, coupled to a secretory signal peptide (SP), can support intercellular transport. However, low secretion efficiency, which may correlate with the positive charge of most CPPs, has emerged as one of the main impediments for efficient intercellular transport. We have reported that a modified Tat-based CPP (Tatm) with reduced positive charge is secreted efficiently, but its transduction activity was greatly reduced. We now show that a triple repeat of Tatm (Tatm3x) with an elongated α-helical amphipathic structure enhances transduction activity and simultaneously retains its secretion efficacy, although passage through the secretory pathway reduces its cell-penetrating activity. SP-Tatm3x supports intercellular transport of fused fluorescent proteins, as well as cell entry and function of a pro-apoptotic peptide. In addition, SP-Tatm3x largely escapes RNA inhibition, which is identified as another potential impediment to CPP-mediated intercellular transport. Expression of SP-Tatm3x in heparan sulfate proteoglycan-negative cells further improves its transduction activity. These results demonstrate the feasibility of intercellular transport of proteins, but further work is needed to better understand the reduction of cell-penetrating activity associated with secretion of CPP-fusion proteins.