Speckled Tracking of Pleura-A Novel Tool for Lung Ultrasound; Distinguishing COVID-19 from Acute Heart Failure.

For the acutely dyspneic patient, discerning bedside between acute decompensated heart failure (ADHF) and COVID-19 is crucial. A lung ultrasound (LUS) is sensitive for detecting these conditions, but not in distinguishing between them; both have bilateral B-lines. The Blue protocol uses pleural sliding to differentiate decreased pneumonia; however, this is not the case in ADHF. Nonetheless, this pleural sliding has never been quantified. Speckled tracking is a technology utilized in the echocardiography field that quantifies the motion of tissues by examining the movement of ultrasound speckles. We conducted a retrospective study of LUS performed in emergency room patients during the COVID-19 pandemic. Speckled tracking of the pleura by applying software to the B-mode of pleura was compared between COVID-19 patients, ADHF patients, and patients with no respiratory complaints. A significant difference was found between the patient groups on speckled tracking both in respect of displacement and velocity. ADHF had the highest displacement, followed by COVID-19, and then non-respiratory patients: 1.63 ± 1.89, 0.59 ± 0.71, and 0.24 ± 0.45, respectively (p < 0.01). A similar trend was seen in velocity with ADHF having the highest velocity 0.34 ± 0.37, followed by COVID-19 0.14 ± 0.71, and non-respiratory patients 0.02 ± 0.09 (p <0.01). Speckled tracking of the pleura is a potential tool for discerning between different causes of dyspnea.

Lean six sigma and stroke in rural hospital - The case of Baruch Padeh Medical Center.

PURPOSE: This case study aims to demonstrate the strengths of the Lean Six Sigma (LSS) methodology to improve the acute ischemic stroke (AIS) treatment rates and reduce process lead time at Baruch Padeh Medical Center (BPMC), a rural hospital in the Galilee region of Northern Israel. The LSS project redefined the BPMC stroke care pathway and increased its efficacy. DESIGN/METHODOLOGY/APPROACH: The LSS methodology was implemented in September 2017 by integrating lean principles and the Six Sigma DMAIC (Define-Measure-Analyze-Improve-Control). Existing procedures, field observation, ad hoc measurement and in-depth interviews were utilized, and the GEMBA method was implemented to identify root cause and improve actions optimizing the stroke pathway. FINDINGS: The presented case shows the usefulness of the LSS methodology in improving quality performance in a rural hospital. The intervention allowed the BPMC to improve the intravenous tissue plasminogen activator (IV-tPA) administration rate (+15.2%), reducing the process lead time. The lead time of door-to-computer tomography decreased from 52 to 26 min, and the door-to-needle time decreased from 94 to 75 min. ORIGINALITY/VALUE: The present case study shows the implementation of the LSS methodology aimed to improve the IV-tPA administration rate and reduce the stroke pathway lead time in a rural hospital. The case demonstrates the potential for the LSS methodology to support the AIS pathway optimization and represents a guide for healthcare organizations located in rural areas.

Are the new PA students helpful to emergency medicine physicians in Israel?

OBJECTIVE: Physician assistants (PA) began training in Israeli EDs in 2016. Physician perspectives were measured to evaluate the clinical contributions of PA students. METHODS: Investigators surveyed members of the Israeli Association of Emergency Medicine Physicians in 2017 to rate whether PA students were helpful in patient care and to explore perceptions about PA students. RESULTS: Those working with a PA student felt they were helpful to very helpful in all of the clinical tasks measured. The majority (85%) of other physicians wanted to work with a PA student in the future. Ordering medications, administering IV fluid therapy, and suturing accounted for 60% of the tasks that physicians wanted to add to PA scope of practice. CONCLUSIONS: PA students were helpful in the ED and were meeting expectations for clinical contributions. Most physicians would like to work with PAs and they would like to see PAs increase their scope of practice.

The human complement receptor type 2 (CR2)/CR1 fusion protein TT32, a novel targeted inhibitor of the classical and alternative pathway C3 convertases, prevents arthritis in active immunization and passive transfer mouse models.

Complement activation in human diseases is characterized by the local covalent deposition of the long-lived C3 fragments iC3b/C3dg/C3d. Previously, TT30, a complement alternative pathway (AP)-selective inhibitor, was designed as a fusion protein linking the first four short consensus repeats (SCRs) of human complement receptor type 2 (CR2) with the first five SCRs of human factor H (fH). TT30 acts by utilizing CR2 SCR1-4 to bind the initially formed iC3b/C3dg/C3d fragments and delivering surface-targeted inhibition of AP C3 and C5 convertases through fH SCR 1-5. In order to combine classical (CP) and lectin (LP) pathway inhibitory abilities employing CR2-mediated targeting, TT32 was developed. TT32 is a CR2-CR1 fusion protein using the first ten SCRs of CR1, chosen because they contain both C3 and C5 convertase inhibitory activity through utilization of decay-acceleration and cofactor activity for both AP and CP. In Wieslab assays, TT32 showed potent inhibition of the CP and AP with IC50 of 11 and 46 nM, respectively. The TT32 inhibitory activity is partially blocked with a molar excess of a competing anti-CR2 mAb, thus demonstrating the importance of the CR2 targeting. TT32 was studied in the type II (CII) collagen-induced arthritis (CIA), an active immunization model, and the CII antibody-induced arthritis (CAIA) passive transfer model. In CIA, injection of 2.0 mg TT32 at day 21 and 28 post disease induction, but not untargeted CR1 alone, resulted in a 51.5% decrease in clinical disease activity (CDA). In CAIA, treatment with TT32 resulted in a 47.4% decrease in CDA. Therefore, a complement inhibitor that targets both the AP and CP/LP C3/C5 convertases was shown to limit complement-mediated tissue damage and inflammation in disease models in which all three complement activation pathways are implicated.

Challenges in Implementing International Standards for the Field Hospital Emergency Department in a Disaster Zone: The Israeli Experience.

BACKGROUND: Medical response to world disasters has too often been poorly coordinated and nonprofessional. To improve this, several agencies, led by the World Health Organization (WHO), have developed guidelines to provide accreditation for Foreign Medical Teams (FMTs). There are three levels, with the highest known as FMT Type-3 providing outpatient as well as inpatient surgical emergency care in addition to inpatient referral care. In November 2016, the WHO certified the Israel Defense Forces Field Hospital as the first FMT Type-3. OBJECTIVES: The objectives of this article are to describe the challenges in implementing these international standards for the field hospital emergency department in a disaster zone. DISCUSSION: There are general standards for all levels of FMTs, as well as specific requirements for the FMT-3. These include a mechanism of appropriate triage, two operating suites, 40 regular beds, four to six intensive care unit beds, radiology facilities, and various staff specialties. Despite the sophistication of the field hospital, there are many challenges. Logistical challenges include constructing the hospital in a disaster zone and equipment issues. There are staff challenges such as becoming oriented to a new and difficult environment. Patient challenges include cultural differences, language barriers, and issues of follow-up. There are often ethical challenges unique to the disaster zone. CONCLUSION: By presenting the experience and challenges of the first FMT Type-3, we hope that more countries can join this initiative and improve disaster care throughout the world.

Ultrasound of Jugular Veins for Assessment of Acute Dyspnea in Emergency Departments and for the Assessment of Acute Heart Failure.

BACKGROUND: When a patient arrives at the emergency department (ED) presenting with symptoms of acute decompensated heart failure (ADHF), it is possible to reach a definitive diagnosis through many different venues, including medical history, physical examination, echocardiography, chest X-ray, and B-type natriuretic peptide (BNP) levels. Point-of-care ultrasound (POCUS) has become a mainstream tool for diagnosis and treatment in the field of emergency medicine, as well as in various other departments in the hospital setting. Currently, the main methods of diagnosis of ADHF using POCUS are pleural B-lines and inferior vena cava (IVC) width and respiratory variation. OBJECTIVES: To examine the potential use and benefits of bedside ultrasound of the jugular veins in the evaluation of dyspneic patients for identification of ADHF. METHODS: A blood BNP level was drawn from each participant at time of recruitment. The area and size of the internal jugular vein (IJV) during inspiration and expiration were examined. RESULTS: Our results showed that the respiratory area change of the IJVs had a specificity and sensitivity of nearly 70% accuracy rate in indentifying ADHF in our ED. CONCLUSIONS: Ultrasound of the IJV may be a useful tool for the diagnosis of ADHF because it is easy to measure and requires little skill. It is also not affected by patient body habitus.

De-freezing frozen patient management.

OBJECTIVE: To compare the effectiveness of two methods in encouraging the consideration of a leap from one patient management routine to another: (i) real-time review of the facts by an external medical team (ii) implementation of the 're-thinking-protocol' ('de-Freezing') by both treating and external medical teams. DESIGN: Students accompanied doctors, nurses and patients as non-interrupting observers. When an obvious gap between the expected and actual findings occurred, it was discussed four times: by two teams (treating team, external medical team) in two discussion modes (real-time review, de-Freezing-questionnaire). The students then recorded if a leap was considered for each discussion. SETTING: The study was conducted in the emergency department of the Baruch Padeh Medical Centre, Poriya, Israel. PARTICIPANTS: All patients were included during times when both medical teams (treating, external) were present. INTERVENTION(S): During 14 periods of 5-7 h each, 459 patients were sampled. In 183 patients, 200 gaps were discovered. RESULTS: The external team considered a leap 76 times, compared with 47 by the treating team (P < 0.001). Using the de-Freezing-protocol, the treating team considered a leap 133 times. Interestingly, even the external team benefited from the de-Freezing protocol and considered a leap 140 times (NS compared to the treating team). CONCLUSIONS: While the importance of timely leaping from one patient management routine to another is emphasized in the training of physicians, medical teams too often fail to do so. The de-Freezing-protocol inexpensively encourages the consideration of a leap beyond what is evoked by the involvement of an external team. The protocol is applicable to all medical processes and should be incorporated into medical practice and education.

Comparison of outcomes of two skills-teaching methods on lay-rescuers' acquisition of infant basic life support skills.

OBJECTIVES: The objective was to determine if lay-rescuers' acquisition of infant basic life support (BLS) skills would be better when skills teaching consisted of videotaping practice and providing feedback on performances, compared to conventional skills-teaching and feedback methods. METHODS: This pilot-exploratory, single-blind, prospective, controlled, randomized study was conducted on November 12, 2007, at the Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. The population under study consisted of all first-year medical students enrolled in the 2007-2008 year. BLS training is part of their mandatory introductory course in emergency medicine. Twenty-three students with previous BLS training were excluded. The remaining 71 were randomized into four and then two groups, with final allocation to an intervention and control group of 18 and 16 students, respectively. All the students participated in infant BLS classroom teaching. Those in the intervention group practiced skills acquisition independently, and four were videotaped while practicing. Tapes were reviewed by the group and feedback was provided. Controls practiced using conventional teaching and feedback methods. After 3 hours, all subjects were videotaped performing an unassisted, lone-rescuer, infant BLS resuscitation scenario. A skills assessment tool was developed. It consisted of 25 checklist items, grouped into four sections: 6 points for "categories" (with specific actions in six categories), 14 points for "scoring" (of accuracy of performance of each action), 4 points for "sequence" (of actions within a category), and 1 point for "order" of resuscitation (complete and well-sequenced categories). Two blinded expert raters were given a workshop on the use of the scoring tool. They further refined it to increase scoring consistency. The main outcome of the study was defined as evidence of better skills acquisition in overall skills in the four sections and in the specific skills sets for actions in any individual category. Data analysis consisted of descriptive statistics. RESULTS: Means and mean percentages were greater in the intervention group in all four sections compared to controls: categories (5.72 [95.33%] and 4.69 [92.66%]), scoring (10.57 [75.50%] and 7.41 [43.59%]), sequence (2.28 [57.00%] and 1.66 [41.50%]), and order of resuscitation (0.96 [96.00%] and 0.19 [19.00%]). The means and mean percentages of the actions (skill sets) in the intervention group were also larger than those of controls in five out of six categories: assessing responsiveness (1.69 [84.50%] and 1.13 [56.50%]), breathing technique (1.69 [93.00%] and 1.13 [47.20%]), chest compression technique (3.19 [77.50%] and 1.84 [46.00%]), activating emergency medical services (EMS) (3.00 [100.00%] and 2.81 [84.50%]), and resuming cardiopulmonary resuscitation (0.97 [97.00%] and 0.47 [47.00%]). These results demonstrate better performance in the intervention group. CONCLUSIONS: The use of videotaped practice and feedback for the acquisition of overall infant BLS skills and of specific skill sets is effective. Observation and participation in the feedback and assessment of nonexperts attempting infant BLS skills appeared to improve the ability of this group of students to perform the task.

Analysis of polypeptide movement in the SecY channel during SecA-mediated protein translocation.

In bacteria most secretory proteins are transported across the plasma membrane by the interplay of the ATPase SecA with the translocation channel formed by the SecY complex; SecA uses cycles of ATP hydrolysis to "push" consecutive segments of a polypeptide substrate through the channel. Here we have addressed the mechanism of this process by following the fate of stalled translocation intermediates. These were generated by using a polypeptide substrate containing a bulky disulfide-bonded loop, thus preventing the final residues from passing through the channel. Protease protection experiments showed that the intermediates were stable in the presence of ATP and could complete translocation once the block was removed. The translocation intermediate was also stable when SecA associated with ATPgammaS, a poorly hydrolyzable ATP analog, or ADP plus AlF(4), which mimics the transition state during ATP hydrolysis. In contrast, when SecA was in its ADP-bound state, the translocating polypeptide moved back into the cytosol, as indicated by the disappearance of the protected fragment. Backsliding was not significantly altered by deletion of the plug domain, a short helix in the center of the SecY channel, but it was slowed down when changes were introduced into the pore ring, the constriction of the hourglass-shaped channel. In all cases, backsliding was significantly slower than forward translocation. Together, these data suggest that SecA binds the polypeptide chain in its ATP state and releases it in the ADP state. The channel itself does not bind the polypeptide chain but provides "friction" that minimizes backsliding when ADP-bound SecA resets to "grab" the next segment of the substrate.

Cross-linked SecA dimers are not functional in protein translocation.

The ATPase SecA is involved in post-translational protein translocation through the SecY channel across the bacterial inner membrane. SecA is a dimer that can dissociate into monomers with translocation activity. Here, we have addressed whether dissociation of the SecA dimer is required for translocation. We show that a dimer in which the two subunits are cross-linked by disulfide bridges is inactive in protein translocation, translocation ATPase, and binding to a lipid bilayer. In contrast, upon reduction of the disulfide bridges, the resulting monomers regain these activities. These data support the notion that dissociation of SecA dimers into monomers occurs during protein translocation.

[Hospitalizations due to falls in the childhood population of northern Israel: a comparison between the years 1993-1995 and 2002-2004].

Previous studies showed that falls from height are a major cause of morbidity in children who live in northern Israel. These studies demonstrated major differences in injury severity between Arab and Jewish children, and noted that more children from the Arab sector were admitted to the Intensive Care Unit (ICU). The objective of this study was to compare the hospitalization rates at Rambam Medical Center in the years 1993-1995 and 2002-2004, and to evaluate selected demographic characteristics of these hospitalizations. We found that the total number of falls increased significantly during the years 2002-2004, and that a dramatic increase in the number of admission to ICU was notable among the Jewish population. These findings suggest that injury prevention programs should be implemented urgently on a national level.

Disulfide bridge formation between SecY and a translocating polypeptide localizes the translocation pore to the center of SecY.

During their biosynthesis, many proteins pass through the membrane via a hydrophilic channel formed by the heterotrimeric Sec61/SecY complex. Whether this channel forms at the interface of multiple copies of Sec61/SecY or is intrinsic to a monomeric complex, as suggested by the recently solved X-ray structure of the Methanococcus jannaschii SecY complex, is a matter of contention. By introducing a single cysteine at various positions in Escherichia coli SecY and testing its ability to form a disulfide bond with a single cysteine in a translocating chain, we provide evidence that translocating polypeptides pass through the center of the SecY complex. The strongest cross-links were observed with residues that would form a constriction in an hourglass-shaped pore. This suggests that the channel makes only limited contact with a translocating polypeptide, thus minimizing the energy required for translocation.

The bacterial ATPase SecA functions as a monomer in protein translocation.

The ATPase SecA drives the post-translational translocation of proteins through the SecY channel in the bacterial inner membrane. SecA is a dimer that can dissociate into monomers under certain conditions. To address the functional importance of the monomeric state, we generated an Escherichia coli SecA mutant that is almost completely monomeric (>99%), consistent with predictions from the crystal structure of Bacillus subtilis SecA. In vitro, the monomeric derivative retained significant activity in various assays, and in vivo, it sustained 85% of the growth rate of wild type cells and reduced the accumulation of precursor proteins in the cytoplasm. Disulfide cross-linking in intact cells showed that mutant SecA is monomeric and that even its parental dimeric form is dissociated. Our results suggest that SecA functions as a monomer during protein translocation in vivo.

Dissociation of the dimeric SecA ATPase during protein translocation across the bacterial membrane.

The ATPase SecA mediates post-translational translocation of precursor proteins through the SecYEG channel of the bacterial inner membrane. We show that SecA, up to now considered to be a stable dimer, is actually in equilibrium with a small fraction of monomers. In the presence of membranes containing acidic phospholipids or in certain detergents, SecA completely dissociates into monomers. A synthetic signal peptide also affects dissociation into monomers. In addition, conversion into the monomeric state can be achieved by mutating a small number of residues in a dimeric and fully functional SecA fragment. This monomeric SecA fragment still maintains strong binding to SecYEG in the membrane as well as significant in vitro translocation activity. Together, the data suggest that the SecA dimer dissociates during protein translocation. Since SecA contains all characteristic motifs of a certain class of monomeric helicases, and since mutations in residues shared with the helicases abolish its translocation activity, SecA may function in a similar manner.