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.

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.

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.

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.

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.

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.

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.

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.

Ultrasonography can replace chest X-rays in the postoperative care of thoracic surgical patients.

OBJECTIVES: Lung ultrasound accurately identifies pulmonary and pleural pathologies. Presently it has not been accepted as a routine examination in the postoperative follow-up of thoracic surgical patients. The present study aimed to compare thoracic ultrasonography with chest X-ray for detecting and clinical relevance of pneumothorax, pleural effusion, and lung consolidation and determine whether ultrasonography could replace chest X-ray as the standard examination after surgery. METHODS: In this blinded, prospective, single-center study, lung ultrasound images were obtained within 2 hours of post-operative routine chest X-ray. A severity score was given to each examination in each technique. Lung ultrasound and chest X-ray results were compared by three methods: absolute comparison of normal to abnormal, the degree of pathology, and the clinical findings' relevance. RESULTS: Eighty patients were enrolled from 2013 to 2017, and 215 ultrasonography images were obtained. For pneumothorax, the precise overlap was found in 129/180 (72%) images. In 24% of examinations, X-ray missed ultrasonography findings. There was an agreement between studies in 80/212 (38%) images for pleural effusion. 60% of pleural effusions were missed by chest X-ray and detected by ultrasonography, and only 2.4% were missed by ultrasound, all very small. Clinically relevant fluid accumulation found a precise match in 80%, and 20% were found only by lung ultrasound. For lung consolidation, a 100% overlap was found with both methods. CONCLUSIONS: Our results suggest that lung ultrasound may replace chest X-ray as the standard examination in the postoperative care of patients undergoing thoracic surgical procedures.

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.

CTGF/CCN2 has a possible detrimental role in the inflammation and the remyelination failure in the early stages of multiple sclerosis.

Connective tissue growth factor (CTGF/CCN2) is a proinflammatory and an oligodendrocyte-differentiating blocking agent. It is found in MS lesions, which raises the possibility of involvement in MS pathogenesis. We found that its CSF and serum levels were higher in RR-MS patients than in controls and for serum compared to PP and SP-MS. Immune cells of both RR-MS and controls secreted CTGF/CCN2, which was enhanced by CD3/CD28 stimulation or by LPS. Anti-CTGF treatment of mice with experimental autoimmune encephalitis ameliorated its clinical severity. CTGF/CCN2 may play a role in the immune pathogenesis of MS and in remyelination failure in early stages of MS.

Unusual presentation of aggressive high-grade B-cell lymphoma of colonic origin: A case report and review of the literature.

Colonic lymphoma is a rare disease. The presented case is unique, being manifested with abrupt onset, including circulatory shock and lactic acidosis as the initial presentation.

Point of Care Lung Ultrasound Injury Score-A simple and reliable assessment tool in COVID-19 patients (PLIS I): A retrospective study.

BACKGROUND: In COVID-19 patients, lung ultrasound is superior to chest radiograph and has good agreement with computerized tomography to diagnose lung pathologies. Most lung ultrasound protocols published to date are complex and time-consuming. We describe a new illustrative Point-of-care ultrasound Lung Injury Score (PLIS) to help guide the care of patients with COVID-19 and assess if the PLIS would be able to predict COVID-19 patients' clinical course. METHODS: This retrospective study describing the novel PLIS was conducted in a large tertiary-level hospital. COVID-19 patients were included if they required any form of respiratory support and had at least one PLIS study during hospitalization. Data collected included PLIS on admission, demographics, Sequential Organ Failure Assessment (SOFA) scores, and patient outcomes. The primary outcome was the need for intensive care unit (ICU) admission. RESULTS: A total of 109 patients and 293 PLIS studies were included in our analysis. The mean age was 60.9, and overall mortality was 18.3%. Median PLIS score was 5.0 (3.0-6.0) vs. 2.0 (1.0-3.0) in ICU and non-ICU patients respectively (p<0.001). Total PLIS scores were directly associated with SOFA scores (inter-class correlation 0.63, p<0.001), and multivariate analysis showed that every increase in one PLIS point was associated with a higher risk for ICU admission (O.R 2.09, 95% C.I 1.59-2.75) and in-hospital mortality (O.R 1.54, 95% C.I 1.10-2.16). CONCLUSIONS: The PLIS for COVID-19 patients is simple and associated with SOFA score, ICU admission, and in-hospital mortality. Further studies are needed to demonstrate whether the PLIS can improve outcomes and become an integral part of the management of COVID-19 patients.

Intensive care unit capacity and mortality in older adults: a three nations retrospective observational cohort study.

BACKGROUND: Intensive care unit (ICU) admissions among older adults are expected to increase, while the benefit remains uncertain. The availability of ICU beds varies between hospitals and between countries and is an important factor in the decision to admit older adults in the ICU. We aimed to assess if a non-restrictive approach to ICU older adults admission is associated with a corresponding change in survival. METHODS: Retrospective cohort study that included patients ≥ 80 years who were admitted to each of the three participating hospitals in Australia, Israel, and the United States (USA), between the years 2006-2015, each with distinct ICU capacities and admission criteria. The primary outcomes were in-hospital mortality and all-cause mortality at 6, 12, 18, and 24 months following index hospitalization. RESULTS: The cohort included 62,866 patients with a mean age of 85.9 ± 4.6 years and 58.8% were women. The ICU admission rates were 22.5%, 2.6% and 2.3% in USA, Australia, and Israel, respectively. We constructed a model for ICU admissions based on the USA cohort (highest availability of ICU beds) and then calculated the expected probabilities for the Israeli and Australian cohorts. For the patients in the highest quintile of the admission model, actual ICU admission rates were 67.6% in USA, 22.1% in Australia and 6.0% in Israel. Of these, in-hospital death rates were 52.3% in Israel, 29.8% in Australia, and 22.1% in USA. Two years after hospital discharge, the survival rates in the USA and Australia were 53%, while in Israel 48%. CONCLUSION: ICU admission of adults ≥ 80 years is associated with increased in-hospital survival compared to ward admission, but survival rates 2 years later are similar.

Real time wire localization by ultrasound during central line insertion improves accurate positioning in all upper torso sites.

PURPOSE: To investigate whether point of care ultrasound can improve central venous catheter tip positioning. MATERIAL AND METHODS: A single center retrospective case control study. We compared the precision of central venous catheter tip positioning between two intensive care units while in only one of the units, we used point of care ultrasound for guidewire identification. RESULTS: 207 cases in which central venous catheter was inserted using point of care ultrasound guided method, compared to 192 controls. The primary outcome of correct placement of the central venous catheter tip was significantly higher in the point of care ultrasound guided group (97.6% vs 88.0% p = 0.001). Central venous catheter tip was located too low among 12% of patients in the control group while in only 2.4% of patients in the point of care ultrasound group (p = 0.001). Logistics regression analysis revealed that the correct placement of central venous catheter tip in the point of care ultrasound group versus the control group had an odds ratio of 4.9 (CI 1.6-14.5 P = 0.004). CONCLUSION: Point of care ultrasound for guidewire identification and localization, while inserting central venous catheter from all upper torso sites, improves precision positioning.

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.

Central venous catheter insertion- guidewire migration ratio: Right heart to inferior vena cava.

BACKGROUND: Central Venous Catheters (CVC) are being used in both intensive care units and general wards for multiple purposes. A previous study Galante et al. (2017) observed that during CVC insertion through Subclavian Vein (SCV) or the Internal Jugular Vein (IJV) the guidewire is sometimes advanced to the Inferior Vena Cava (IVC), and at other times to the right atrium. The rate of IVC wire cannulation and the association with side and point of insertion is unknown. OBJECTIVE: In this study, we describe guidewire migration location during real time CVC cannulation (right atrium versus IVC) and report the association between the insertion site and side of the CVC and the location of guidewire migration, Right Atrium (RA)/Right Ventricle (RV) versus IVC guidewire migration. METHODS: This is a retrospective study in the medical intensive care unit among patients that have received CVC during the study years 2014-2020. The rate of IVC versus right atrium/right ventricle wire migration during the procedure were analyzed. The association between the side and point of CVC insertion and the wire migration site was analyzed as well. RESULTS: One hundred and sixty-six patients were enrolled. 33.7% of wires migrated to the IVC and 66.3% to the versus right atrium/right ventricle. The rate of wire migration to the IVC was similar in the IJV site and the SCV site. There was no association between the side of CVC insertion and wire migration to the IVC. CONCLUSION: About a third of all wire migrations, during CVC Seldinger technique insertion, were identified in the IVC, with no potential for wire associated arrhythmia. There was no association between CVC insertion point (SCV versus IJV) nor the side of insertion and the site of guidewire migration.

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".