Intravenous immunoglobulin efficacy on pembrolizumab induced severe toxic epidermal necrolysis.

Pembrolizumab is an immune checkpoint inhibitor used in many different cancers. Several immune-related adverse events (irAEs) have been associated with pembrolizumab, including toxic epidermal necrolysis. Here, we are presenting a patient with non-small cell lung cancer that developed toxic epidermal necrolysis 3-days following initiation of pembrolizumab. Following high-dose steroid therapy, intravenous immunoglobulin 2 g/kg was initiated and resulted in complete resolution of all his irAEs. To our knowledge, this is the first reported case of total re-epithelialization and resolution of immune checkpoint inhibitor-induced toxic epidermal necrolysis following the use of intravenous immunoglobulin.

A randomized, controlled, blinded evaluation of augmenting point-of-care ultrasound and remote telementored ultrasound in inexperienced operators.

BACKGROUND: Handheld ultrasound devices present an opportunity for prehospital sonographic assessment of trauma, even in the hands of novice operators commonly found in military, maritime, or other austere environments. However, the reliability of such point-of-care ultrasound (POCUS) examinations by novices is rightly questioned. A common strategy being examined to mitigate this reliability gap is remote mentoring by an expert. OBJECTIVES: To assess the feasibility of utilizing POCUS in the hands of novice military or civilian emergency medicine service (EMS) providers, with and without the use of telementoring. To assess the mitigating or exacerbating effect telementoring may have on operator stress. METHODS: Thirty-seven inexperienced physicians and EMTs serving as first responders in military or civilian EMS were randomized to receive or not receive telementoring during three POCUS trials: live model, Simbionix trainer, and jugular phantom. Salivary cortisol was obtained before and after the trial. Heart rate variability monitoring was performed throughout the trial. RESULTS: There were no significant differences in clinical performance between the two groups. Iatrogenic complications of jugular venous catheterization were reduced by 26% in the telementored group (P < 0.001). Salivary cortisol levels dropped by 39% (P < 0.001) in the telementored group. Heart rate variability data also suggested mitigation of stress. CONCLUSIONS: Telementoring of POCUS tasks was not found to improve performance by novices, but findings suggest that it may mitigate caregiver stress.

Outcomes prediction in longitudinal data: Study designs evaluation, use case in ICU acquired sepsis.

Outcomes' prediction in Electronic Health Records (EHR) and specifically in Critical Care is increasingly attracting more exploration and research. In this study, we used clinical data from the Intensive Care Unit (ICU), focusing on ICU acquired sepsis. Looking at the current literature, several evaluation approaches are reported, inspired by epidemiological designs, in which some do not always reflect real-life application's conditions. This problem seems relevant generally to outcomes' prediction in longitudinal EHR data, or generally longitudinal data, while in this study we focused on ICU data. Unlike in most previous studies that investigated all sepsis admissions, we focused specifically on ICU-Acquired Sepsis. Due to the sparse nature of the longitudinal data, we employed the use of Temporal Abstraction and Time Interval-Related Patterns discovery, which are further used as classification features. Two experiments were designed using three different outcomes prediction study designs from the literature, implementing various levels of real-life conditions to evaluate the prediction models. The first experiment focused on predicting whether a patient would suffer from ICU-acquired sepsis and when during her admission, given a sliding observation time window, and the comparison of the three study designs behavior. The second experiment focused only on predicting whether the patient will suffer from ICU-acquired sepsis, based on data taken relatively to his admission start time. Our results show that using Temporal Discretization for Classification (TD4C) led to better performance than using the Equal-Width Discretization, Knowledge-Based, or SAX. Also, using two states abstraction was better than three or four. Using the default Binary TIRP representation method performed better than Mean Duration, Horizontal Support, and horizontally normalized horizontal support. Using XGBoost as a classifier performed better than Logistic Regression, Neural Net, or Random Forest. Additionally, it is demonstrated why the use of case-crossover-control is most appropriate for real life application conditions evaluation, unlike other incomplete designs that may even result in "better performance".

Accurate positioning of extracorporeal membrane oxygenation cannulas using real-time trans-thoracic echocardiography.

In this retrospective observational case series, we aimed to evaluate the use of real-time trans-thoracic echocardiography in accurate positioning of extracorporeal membrane oxygenation cannulas. Patients admitted to the intensive care unit with severe adult respiratory distress syndrome in need for extracorporeal membrane oxygenation were screened. Twenty-one extracorporeal membrane oxygenation cannulas were inserted in 10 patients, and 95% of the cannulas were located exactly at the vena cava-right atria junction as planned. Real-time point-of-care trans-thoracic echocardiography for the exact positioning of extracorporeal membrane oxygenation cannula is feasible, simple, time saving, and accurate.

The Effect of ARDS on Survival: Do Patients Die From ARDS or With ARDS?

OBJECTIVE:: To investigate the contribution of acute respiratory distress syndrome (ARDS) in of itself to mortality among ventilated patients. DESIGN AND SETTING:: A longitudinal retrospective study of ventilated intensive care unit (ICU) patients. PATIENTS:: The analysis included patients ventilated for more than 48 hours. Patients were classified as having ARDS on admission (early-onset ARDS), late-onset ARDS (ARDS not present during the first 24 hours of admission), or no ARDS. Primary outcomes were mortality at 28 days, and secondary outcomes were 2-year mortality rate from ICU admission. RESULTS:: A total of 1411 ventilated patients were enrolled: 41% had ARDS on admission, 28.5% developed ARDS during their ICU stay, and 30.5% did not meet the ARDS criteria prior to ICU discharge or death. The non-ARDS group was used as the control. We also divided the cohort based on the severity of ARDS. After adjusting for covariates, mortality risk at 28 days was not significantly different among the different groups. Both early- and late-onset ARDS as well as the severity of ARDS were found to be significant risk factors for 2 years from ICU survival. CONCLUSION:: Among patients who were ventilated on ICU admission, neither the presence, the severity, or the timing of ARDS contribute independently to the short-term mortality risk. However, acute respiratory distress syndrome does contribute significantly to 2-year mortality risk. This suggests that patients may not die acutely from ARDS itself but rather from the primary disease, and during the acute phase of ARDS, clinicians should focus on improving treatment strategies for the diseases that led to ARDS.

Single-Operator Ultrasound-Guided Central Venous Catheter Insertion Verifies Proper Tip Placement.

OBJECTIVES: To evaluate whether a single-operator ultrasound-guided, right-sided, central venous catheter insertion verifies proper placement and shortens time to catheter utilization. DESIGN: Prospective observational study with historical controls. SETTING: Adult ICUs. PATIENTS: Sixty-four consecutive patients undergoing ultrasound-assisted right-sided central venous catheterization compared with 92 serial historic controls who had unassisted central catheter insertion at the same sites. INTERVENTIONS: Subcostal transthoracic echocardiography during catheter insertion. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the correct placement of the catheter tip determined by postprocedural chest radiography. The subclavian site was used in 41 patients (64%) (inserted without ultrasound guidance) in the ultrasound-assisted group and 62 (67%) in the control group, whereas the jugular vein was used in the remaining patients. The tip was accurately positioned in 59 of 68 patients (86.7%) in the ultrasound-assisted group compared with 51 of 94 (54.8%) in the control group (p < 0.001). The median time from end of the procedure to catheter utilization after chest radiography approval was 2.4 hours. CONCLUSIONS: A single-operator ultrasound-guided central venous catheter insertion is effective in verifying proper tip placement and shortens time to catheter utilization.

Quantifying the Mortality Impact of Do-Not-Resuscitate Orders in the ICU.

OBJECTIVES: We quantified the 28-day mortality effect of preexisting do-not-resuscitate orders in ICUs. DESIGN: Longitudinal, retrospective study of patients admitted to five ICUs at a tertiary university medical center (Beth Israel Deaconess Medical Center, BIDMC, Boston, MA) between 2001 and 2008. INTERVENTION: None. PATIENTS: Two cohorts were defined: patients with do not resuscitate advance directives on day 1 of ICU admission and a control group comprising patients with no limitations of level of care on ICU day 1 (full code). MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality at 28 days after ICU admission. Of 19,007 ICU patients, 1,239 patients (6.5%) had a do-not-resuscitate order on the first day of ICU admission and survived 48 hours in the ICU. We matched those do-not-resuscitate patients with 2,402 patients with full-code status. Twenty-eight day and 1-year mortality were both significantly higher in the do-not-resuscitate group (33.9% vs 18.4% and 60.7% vs 40.2%; p < 0.001, respectively). CONCLUSION: Do-not-resuscitate status is an independent risk factor for ICU mortality. This may reflect severity of illness not captured by other clinical factors, but the perceptions of the treating team related to do-not-resuscitate status could also be causally responsible for increased mortality in patients with do-not-resuscitate status.

The feasibility and efficacy of implementing a focused cardiac ultrasound course into a medical school curriculum.

BACKGROUND: Teaching cardiac ultrasound to medical students in a brief course is a challenge. We aimed to evaluate the feasibility of teaching large groups of medical students the acquisition and interpretation of cardiac ultrasound images using a pocket ultrasound device (PUD) in a short, specially designed course. METHODS: Thirty-one medical students in their first clinical year participated in the study. All were novices in the use of cardiac ultrasound. The training consisted of 4 hours of frontal lectures and 4 hours of hands-on training. Students were encouraged to use PUD for individual practice. Finally, the students' proficiency in the acquisition of ultrasound images and their ability to recognize normal and pathological states were evaluated. RESULTS: Sixteen of 27 (59%) students were able to demonstrate all main ultrasound views (parasternal, apical, and subcostal views) in a six-minute test. The most obtainable view was the parasternal long-axis view (89%) and the least obtainable was the subcostal view (58%). Ninety-seven percent of students correctly differentiated normal from severely reduced left ventricular function, 100% correctly differentiated a normal right ventricle from a severely hypokinetic one, 100% correctly differentiated a normal mitral valve from a rheumatic one, and 88% correctly differentiated a normal aortic valve from a calcified one, while 95% of them correctly identified the presence of pericardial effusion. CONCLUSIONS: Training of medical students in cardiac ultrasound during the first clinical year using a short, focused course is feasible and enables students with modest ability to acquire the main transthoracic ultrasound views and gain proficiency in the diagnosis of a limited number of cardiac pathologies.

Self-learning of cardiac ultrasound by medical students: can augmented online training improve and maintain manual POCUS skills over time?

BACKGROUND: The use of cardiac point of care ultra-sound is rapidly growing and so is the demand for quality POCUS teaching. POCUS teaching is usually conducted in small groups requiring much space and equipment. This study attempts to test whether providing access to an E-learning module as an adjunct to a cardiac POCUS course can increase students' image acquisition skills. This will show POCUS teaching can improve significantly without having to invest a significant amount of resources. METHODS: Medical students (N = 125) were divided into two groups and had undergone a hands-on Cardiac POCUS course before their internal clerkship. During the clerkship, members of both groups got to practice their POCUS skills in the internal wards. One group was provided with accounts to a cardiac POCUS teaching E-learning platform (eMedical Academy©). After limited time for self- practice, both groups underwent a pre-validated ultrasound examination. The two groups' test results were then compared for each POCUS view and for the total exam score. RESULTS: The E-learning group performed significantly better than the course-only group in the 6-min exam total score, and at acquiring the following views: parasternal long axis view, apical four-chamber view, and the inferior vena cava view. CONCLUSION: E-learning platforms can be an efficient tool for improving cardiac POCUS teaching and maintaining POCUS skills. Using it as a supplement to a hands-on course provides better POCUS skills without the need of extra hands-on teaching.

The effect of real-time EF automatic tool on cardiac ultrasound performance among medical students.

PURPOSE: Point-of-care ultrasound (POCUS) is a sensitive, safe, and efficient tool used in many clinical settings and is an essential part of medical education in the United States. Numerous studies present improved diagnostic performances and positive clinical outcomes among POCUS users. However, others stress the degree to which the modality is user-dependent, rendering high-quality POCUS training necessary in medical education. In this study, the authors aimed to investigate the potential of an artificial intelligence (AI) based quality indicator tool as a teaching device for cardiac POCUS performance. METHODS: The authors integrated the quality indicator tool into the pre-clinical cardiac ultrasound course for 4th-year medical students and analyzed their performances. The analysis included 60 students who were assigned to one of two groups as follows: the intervention group using the AI-based quality indicator tool and the control group. Quality indicator users utilized the tool during both the course and the final test. At the end of the course, the authors tested the standard echocardiographic views, and an experienced clinician blindly graded the recorded clips. Results were analyzed and compared between the groups. RESULTS: The results showed an advantage in quality indictor users' median overall scores (P = 0.002) with a relative risk of 2.3 (95% CI: 1.10, 4.93, P = 0.03) for obtaining correct cardiac views. In addition, quality indicator users also had a statistically significant advantage in the overall image quality in various cardiac views. CONCLUSIONS: The AI-based quality indicator improved cardiac ultrasound performances among medical students who were trained with it compared to the control group, even in cardiac views in which the indicator was inactive. Performance scores, as well as image quality, were better in the AI-based group. Such tools can potentially enhance ultrasound training, warranting the expansion of the application to more views and prompting further studies on long-term learning effects.

A Comparison of Online Self-Training and Standard Bedside Training in Lung Ultrasonography for Medical Students.

PURPOSE: Point-of-care ultrasonography (POCUS) is increasingly integrated into medical education. Traditionally taught at the bedside using a hands-on approach, POCUS is limited by cost, time, faculty availability, and access to POCUS resources. With the recent transition to digitalization in medical education, the authors compare lung POCUS performance and pathology identification among medical students to examine whether using an online, self-learning lung POCUS module is noninferior to traditional bedside, faculty-led lung POCUS training. METHOD: This study assessed the performance of 51 medical students from August to October 2021 on an elearning lung POCUS course with traditional bedside training and no training. POCUS students were scored on use of a simulator to identify pathologies, ability to identify lung ultrasonographic pathological clips, and scanning technique. RESULTS: The elearning group had a significantly higher median (interquartile range [IQR]) total test score (15/18 [10.5-16] vs. 12/18 [9-13]; P = .03) and scanning technique score (5/5 [4-5] vs. 4/5 [3-4]; P = .03) compared with the standard curriculum group. The median (IQR) accuracy in the clip segment of the examination was 7.5 of 10 (4-9) in the self-learning group and 6 of 10 (4-7) in the standard curriculum group ( P = .18). The median (IQR) grade on the simulator segment of the examination was 2 of 3 (2-3) in the self-learning group and 2 of 3 (1-2) in the standard curriculum group ( P = .06). CONCLUSIONS: This study suggests that self-directed elearning of lung POCUS is at least noninferior to bedside teaching and possibly even a superior method of learning lung POCUS. This teaching method POCUS is feasible for medical students to learn lung ultrasonography and has potential to complement or augment the traditional learning process or eliminate or lessen the requirement for bedside teaching by reaching a larger audience while minimizing costs and human resources.

Real-World experience with efgartigimod in patients with myasthenia gravis.

Recommendations for the treatment of myasthenia gravis (MG) have been difficult to develop because of limited evidence from large randomized controlled trials. New drugs and treatment approaches have recently been shown to be effective in phase 3 studies in seropositive generalized (g) MG. One such drug is efgartigimod, a human-Fc-fragment of IgG1, with a high affinity for the endosomal FcRn. We conducted a multicenter study to evaluate the real-world clinical and safety effects of efgartigimod in 22 gMG patients. We evaluated the strategies for the timing of re-treatment with it. The participants received a total of 59 efgartigimod -treatment cycles. The median number of cycles was 2 (range 1-6). Twenty patients (86.3%) improved by at least 2 MG-ADL points after the first treatment cycle. The median MG-ADL score at baseline was 6.5 (range: 3-17) and 2.5 (range: 0-9) post-treatment (p < 0.001). A consistent improvement of at least 2 points in the MG-ADL score after each cycle occurs in 18 patients. The effect duration of the treatment was usually between 4 and 12 weeks. Two major clinical patterns of treatment response were found. Treatment with efgartigimod was also associated with significant reductions of prednisone doses Overall, the treatment was safe and associated with only minor adverse events. The single fatality was apparently due tosevere respiratory failure. We found that efgartigimod is clinically effective, may be used as a steroid sparing agent and is generally safe for gMG patients. We recommend a personalized preventive treatment approach until clinical stabilization, followed by discontinuation and periodic evaluations.

Lung ultrasound is associated with distinct clinical phenotypes in COVID-19 ARDS: A retrospective observational study.

BACKGROUND: ARDS is a heterogeneous syndrome with distinct clinical phenotypes. Here we investigate whether the presence or absence of large pulmonary ultrasonographic consolidations can categorize COVID-19 ARDS patients requiring mechanical ventilation into distinct clinical phenotypes. METHODS: This is a retrospective study performed in a tertiary-level intensive care unit in Israel between April and September 2020. Data collected included lung ultrasound (LUS) findings, respiratory parameters, and treatment interventions. The primary outcome was a composite of three ARDS interventions: prone positioning, high PEEP, or a high dose of inhaled nitric oxide. RESULTS: A total of 128 LUS scans were conducted among 23 patients. The mean age was 65 and about two-thirds were males. 81 scans identified large consolidation and were classified as "C-type", and 47 scans showed multiple B-lines with no or small consolidation and were classified as "B-type". The presence of a "C-type" study had 2.5 times increased chance of receiving the composite primary outcome of advanced ARDS interventions despite similar SOFA scores, Pao2/FiO2 ratio, and markers of disease severity (OR = 2.49, %95CI 1.40-4.44). CONCLUSION: The presence of a "C-type" profile with LUS consolidation potentially represents a distinct COVID-19 ARDS subphenotype that is more likely to require aggressive ARDS interventions. Further studies are required to validate this phenotype in a larger cohort and determine causality, diagnostic, and treatment responses.

Artificial Intelligence (AI) versus POCUS Expert: A Validation Study of Three Automatic AI-Based, Real-Time, Hemodynamic Echocardiographic Assessment Tools.

BACKGROUND: Point Of Care Ultra-Sound (POCUS) is an operator dependent modality. POCUS examinations usually include 'Eyeballing' the inspected anatomical structure without conducting accurate measurements due to complexity and insufficient time. Automatic real time measuring tools can make accurate measurements fast and simple and dramatically increase examination reliability while saving the operator much time and effort. In this study we aim to assess three automatic tools which are integrated into the Venue™ device by GE: the automatic ejection fraction, velocity time integral, and inferior vena cava tools in comparison to the gold standard-an examination by a POCUS expert. METHODS: A separate study was conducted for each of the three automatic tools. In each study, cardiac views were acquired by a POCUS expert. Relevant measurements were taken by both an auto tool and a POCUS expert who was blinded to the auto tool's measurement. The agreement between the POCUS expert and the auto tool was measured for both the measurements and the image quality using a Cohen's Kappa test. RESULTS: All three tools have shown good agreement with the POCUS expert for high quality views: auto LVEF (0.498; p < 0.001), auto IVC (0.536; p = 0.009), and the auto VTI (0.655; p = 0.024). Auto VTI has also shown a good agreement for medium quality clips (0.914; p < 0.001). Image quality agreement was significant for the auto EF and auto IVC tools. CONCLUSIONS: The Venue™ show a high agreement with a POCUS expert for high quality views. This shows that auto tools can provide reliable real time assistance in performing accurate measurements, but do not reduce the need of a good image acquisition technique.

Can Dialysis Patients Identify and Diagnose Pulmonary Congestion Using Self-Lung Ultrasound?

BACKGROUND: With the recent developments in automated tools, smaller and cheaper machines for lung ultrasound (LUS) are leading us toward the potential to conduct POCUS tele-guidance for the early detection of pulmonary congestion. This study aims to evaluate the feasibility and accuracy of a self-lung ultrasound study conducted by hemodialysis (HD) patients to detect pulmonary congestion, with and without artificial intelligence (AI)-based automatic tools. METHODS: This prospective pilot study was conducted between November 2020 and September 2021. Nineteen chronic HD patients were enrolled in the Soroka University Medical Center (SUMC) Dialysis Clinic. First, we examined the patient's ability to obtain a self-lung US. Then, we used interrater reliability (IRR) to compare the self-detection results reported by the patients to the observation of POCUS experts and an ultrasound (US) machine with an AI-based automatic B-line counting tool. All the videos were reviewed by a specialist blinded to the performer. We examined their agreement degree using the weighted Cohen's kappa (Kw) index. RESULTS: A total of 19 patients were included in our analysis. We found moderate to substantial agreement between the POCUS expert review and the automatic counting both when the patient performed the LUS (Kw = 0.49 [95% CI: 0.05-0.93]) and when the researcher performed it (Kw = 0.67 [95% CI: 0.67-0.67]). Patients were able to place the probe in the correct position and present a lung image well even weeks from the teaching session, but did not show good abilities in correctly saving or counting B-lines compared to an expert or an automatic counting tool. CONCLUSIONS: Our results suggest that LUS self-monitoring for pulmonary congestion can be a reliable option if the patient's count is combined with an AI application for the B-line count. This study provides insight into the possibility of utilizing home US devices to detect pulmonary congestion, enabling patients to have a more active role in their health care.

Severity of a Vipera palaestinae envenomation objective findings associated with a complicated hospitalization course following a Vipera palaestinae bite.

The most common snake in Israel, responsible for most snakebites is Vipera palaestinae (VP). Envenomation signs and symptoms vary from local manifestations to systemic reactions that may end with death. Antivenom treatment, given to high-risk patients, reduces complications and mortality but carries risks. As of now, there is no standardized protocol for adults bitten by VP based on objective clinical and laboratory findings. We conducted A retrospective analysis of 159 patients admitted to two large tertiary care institutions in the center (Hadassah University Medical Center) and south (Soroka University Medical Center) of Israel with Vipera palaestinae bites during 1990-2017. Epidemiological and clinical data were extracted, and the patients were divided into two groups based on hospitalization time (over or under 48 h). 159 patients were included in this study. The average hospitalization time was 66.1 h, with 49.7% of patients admitted over 48 h. The main factors that statistically correlated with a longer hospitalization time were: Male gender, lower extremity bite, platelets lower than 150 K at presentation, leukocyte count of over 10 K at presentation and elevated D-Dimer levels. This study provides factors which are associated with a severe VP envenomation. These clinical or laboratory findings (along with accompanying clinical symptoms) are associated with a higher risk of a prolonged hospitalization with more complications and may require a more intensive treatment and monitoring.

Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study.

Pulmonary arterial hypertension (PAH) is a rare condition with the potential to progress to right heart failure. Point-of-Care Ultrasonography (POCUS), used and interpreted in real time at the bedside to further the cardiopulmonary assessment, has the potential to improve the longitudinal care of PAH patients in the ambulatory setting. Patients from PAH clinics at two academic medical centers were randomized to either a POCUS assessment cohort or non-POCUS standard care (ClinicalTrials.gov identifier NCT05332847). The POCUS group received blinded heart, lung, and vascular ultrasound assessments. Thirty-six patients were randomized to the study and followed over time. Mean age was 65 in both groups and majority female (76.5% and 88.9% females in POCUS and control, respectively). Median time for POCUS assessment was 11 min (range 8-16). There were significantly more changes in management in the POCUS group than control (73% vs. 27%, p-value < 0.001). Multivariate analysis revealed that management changes were more likely to occur with a POCUS assessment, with an odds ratio (OR) of 12 when POCUS was added to physical exam vs. OR of 4.6 compared to physical examination alone (p < 0.001). POCUS in the PAH clinic is feasible and, when combined with physical examination, increases the number of findings and results in changes in management without significantly prolonging visit encounters. POCUS may help support clinical evaluation and decision making in ambulatory PAH clinics.