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Sarah Sharman Moser,1 Lior Apter,1,2 Idit Livnat,3 Roni Ginsburg,3 Adva Yarden,3 Michal Drori,1 Anat Drizon,1 Gabriel Chodick,1,4 Nava Siegelmann-Danieli1,4 1Maccabi Institute for Research and Innovation (Maccabitech), Maccabi Healthcare Services, Tel Aviv, Israel; 2Department of Health Systems Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 3Medical Affairs, AstraZeneca, Kefar Sava, Israel; 4Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Sarah Sharman Moser, Email moser_sa@mac.org.ilBackground: In this observational study, we analyzed the treatment patterns and clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) who developed brain metastases during their disease in a 2.7 million-member public health-provider in Israel.Methods: Newly diagnosed patients with mBC who initiated first-line treatment between January 2013 and June 2021 were identified. Time on treatment (ToT) and overall survival (OS) were assessed at a minimum of 6 months follow-up (cutoff: December 2021).Results: We identified a total of 61 patients: 98.4% females, median age 50 years (IQR = 44– 63), 85% invasive ductal tumors, 44% hormone receptor positive, 51% performance status 0– 1. The median duration of follow-up was 6.2 years. All patients initiated a combination treatment of trastuzumab, pertuzumab, and chemotherapy (TPC), and 72% moved to second-line treatment during the study follow-up period (82% ado-trastuzumab emtansine). The median ToT for first-line and second-line treatments were 16.9 months (95% CI = 13.9– 27.7) and 7.9 months (95% CI = 5.6– 10.9), respectively. The median overall survival (OS) was 45.5 months (95% CI = 35.4– 71.2) from the initiation of first-line treatment. When considering the timing of brain metastases, the median OS was 36.3 months (95% CI = 10.0–NR) for those diagnosed upfront (n = 15, 25%), 59.1 months (95% CI = 32.5–NR) for those diagnosed while on TPC (n = 25, 41%), and 40.8 months (95% CI = 35.4–NR) for those diagnosed at a later stage (n = 21, 34%). The median OS from brain metastases diagnosis was 25.1 months (95% CI = 17.0– 34.6).Conclusion: Patients with upfront brain involvement at the time of mBC diagnosis had shorter survival compared to those who started TPC without brain metastases. Nonetheless, the overall results from this study compare favorably with previous studies and contribute to understanding the value of traditional treatment options, which will serve as a baseline for future treatment strategies in the real-world setting.Keywords: HER2 positive, metastatic, breast cancer, observational study, real-world

Summary Reasons for performing study: Initial assessment of the mortality rates and prognostic indicators in horses with colic presented to a referral hospital in Israel. Objectives: To determine mortality rates and to identify potential prognostic indicators in horses undergoing treatment for colic. Methods: The medical records of 208 colic cases were reviewed and mortality rates calculated including 95% confidence intervals. Mortality rates in surgical cases were calculated separately for strangulating and nonstrangulating lesions as well as for lesions of the large and small intestines. Potential prognostic indicators were identified and evaluated by Student's t test or X [ABSTRACT FROM AUTHOR]

The functional behaviour and pharmacological responses of ring segments of large coronary arteries removed from five patients undergoing cardiac transplantation were studied in vitro. All segments showed spontaneous rhythmic contractions which were markedly dependent on external calcium and were rapidly abolished in calcium-free solutions and by verapamil. The contractions were inhibited by cooling and by anoxia. Phasic activity was enhanced by increasing the external potassium concentration over the range 5 to 20 mmol·litre−1 but was abolished by 120 mmol·litre−1 potassium. Noradrenaline and ergonovine enhanced or induced phasic activity. The behaviour of human coronary arteries resembles that of the portal-mesenteric veins of many species and our results suggest that the activation mechanisms of these two tissues may be similar. [ABSTRACT FROM PUBLISHER]

Presents an approach to resolve the potential dilemma of treating patients with vascular disease in the U.S. Development of low-profile, high-pressure coronary balloon catheters; Use of laser-assisted angioplasty; Clinical evaluation of patients by a vascular surgeon or a cardiologist specializing in peripheral vascular disease.

There are few comprehensive studies on the condition of reefs that are remote from direct anthropogenic pressures and, therefore, ecological baseline data are scarce. To help address this deficiency, the community condition of the little-studied remote reefs along a 200-km-long tract bordering the Gulf of Batabano (southwest Cuba) was assessed. The reef-front coral communities (38 sites), where Montastraea spp. is the most common coral, were homogeneous along the entire reef tract. The reef-crest coral communities (30 sites), however, could be differentiated into three geographically distinct areas by their abundances of Acropora palmata and Diploria clivosa; the former predominated at 26 of the 30 reef-crest sites, but most colonies were "standing dead". This observation is similar to the massive declines of acroporid coral populations that have been documented throughout the Caribbean region. Mean coral cover (19-26%) was similar to the regional average (19-23%), but was surprisingly high (72%) at a protected reef-crest site close to an extensive mainland coastal mangrove (Ciénaga de Zapata). At this site, A. palmata and other acroporids were abundant and healthy, and Diadema antillarum density was higher than in the other surveyed areas. Reduced hurricane impact at this more sheltered site may have either circumvented a synergy with overfishing, hurricane destruction, and recruitment failure (widely reported at other degraded reefs), or maintained a high diademid population that facilitated coral recruitment and allowed rapid coral recovery following damage. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum., Methods: We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments., Results: Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop., Conclusion: After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To examine the effectiveness of individual versus group therapy for anxiety and depression among university students. Participants: Forty-one university students experiencing moderate to severe symptoms of anxiety and/or depression participated during one of three academic semesters from 2015 to 2016. Methods: Participants were randomly assigned to either 6-weeks of individual or group therapy and completed outcome measures at pre-and-post-treatment. Results: Significant reductions in both depression and anxiety scores were found across time, with no significant difference between group and individual therapy outcomes. Exploratory analysis of attitudes toward therapy found that while individual therapy was rated more favorably than group therapy overall, attitudes toward therapy became more favorable from pre to post-treatment for all participants. An interaction showed differences in attitudes toward individual and group therapy according to participants' randomly assigned treatment. Conclusions: These findings support the increased usage of group therapy within university counseling centers, with implications for stepped care discussed.

Purpose: To present a unique case of streptococcus dysgalactiae keratitis with progression to corneal perforation and endophthalmitis, in the setting of epidermal growth factor receptor inhibitor (erlotinib) therapy for advanced non-small cell lung cancer., Observations: An 89-year-old female with non-small cell lung cancer on erlotinib presented with corneal perforation due to infectious keratitis. Microbial cultures grew streptococcus dysgalactiae, a virulent pathogen known to affect immunocompromised patients that has not been previously described to cause infectious keratitis. Despite aggressive medical intervention, the clinical course was complicated by rapid progression to no light perception visual acuity in the setting of endophthalmitis with orbital cellulitis, necessitating evisceration., Conclusions and Importance: Epidermal growth factor receptor inhibitor therapy can result in significant ocular complications including dry eyes, epithelial keratopathy, non-healing abrasions, infectious keratitis, and rarely, corneal melting and perforation. These side effects can predispose patients to aggressive infections with rare organisms, highlighting the importance of understanding the ocular side effects of systemic chemotherapeutic agents., Competing Interests: The following authors have no financial disclosures (EKS, SA, KI, JP, CA, KE, DDR, RG). All authors attest that they meet the current ICMJE criteria for Authorship., (© 2020 The Author(s).)

An African American girl born at 37 weeks via spontaneous vaginal delivery to a 33-year-old woman was noted on delivery to have a unilateral absent red reflex in the right eye, which was enlarged. Intraocular pressure was elevated, and the cornea had a straw-colored opacity. B-scan ultrasonography of the right eye showed diffuse hyperechoic vitreous opacities and a retrolental mass, with a hyperechoic band stretching from the optic disk to the posterior lens. Neuroimaging showed a unilateral enlarged globe, intraocular hemorrhage, and persistent fetal vasculature, with no other intracranial pathology. An anterior chamber washout revealed liquified blood; the presence of corneal blood staining was confirmed. A spontaneous intraocular hemorrhage associated with persistent fetal vasculature was suspected, leading to secondary glaucoma and corneal blood staining., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices., Methods: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time., Results: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0)., Conclusions: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.)., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions. The methodology has been designed to meet specifications for GMP production, required for manufacture of advanced therapy medicinal products (ATMPs). In a porcine model of severe liver failure, damage was assured in all animals by surgical ischaemia in pigs with human sized livers (1.2-1.6 kg liver weights). The BioArtificial liver (UCLBAL) improved important prognostic clinical liver-related parameters, eg, a significant improvement in coagulation, reduction in vasopressor requirements, improvement in blood pH and in parameters of intracranial pressure (ICP) and oxygenation.

A new stepped care model developed in North America reimagines the original United Kingdom model for the modern university campus environment. It integrates a range of established and emerging online mental health programs systematically along dimensions of treatment intensity and associated student autonomy. Program intensity can be either stepped up or down depending on level of client need. Because monitoring is configured to give both provider and client feedback on progress, the model empowers clients to participate actively in care options, decisions, and delivery. Not only is stepped care designed to be more efficient than traditional counseling services, early observations suggest it improves outcomes and access, including the elimination of service waitlists. This paper describes the new model in detail and outlines implementation experiences at 3 North American universities. While the experiences implementing the model have been positive, there is a need for development of technology that would facilitate more thorough evaluation. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Objective: To determine physician-reported adherence to and support of the 2010 Massachusetts youth concussion law, as well as barriers to care and clinical practice in the context of legislation., Study Design: Primary care physicians (n = 272) in a large pediatric network were eligible for a cross-sectional survey in 2014. Survey questions addressed key policy and practice provisions: concussion knowledge, state regulations and training, practice patterns, referrals, patient characteristics, and barriers to care. Analyses explored relationships between practice and policy, adjusting for physician demographic and practice characteristics., Results: The survey response rate was 64% among all responders (173 of 272). A total of 146 respondents who had evaluated, treated, or referred patients with a suspected sports-related concussion in the previous year were eligible for analysis. The vast majority (90%) of providers agreed that the current Massachusetts laws regarding sports concussions are necessary and support the major provisions. Three-quarters (74%) had taken a required clinician training course on concussions. Those who took training courses were significantly more likely to develop individualized treatment plans (OR, 3.6; 95% CI, 1.1-11.0). Physician training did not improve screening of youth with concussion for depression or substance use. Most physicians (77%) advised patients to refrain from computer, telephone, or television for various time periods. Physicians reported limited communication with schools., Conclusions: Primary care physicians report being comfortable with the diagnosis and management of concussions, and support statewide regulations; however, adherence to mandated training and specific legal requirements varied. Broader and more frequent training may be necessary to align current best evidence with clinical care and state-mandated practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Valuable correlations could be made between serum prostate specific antigen (PSA) and prostate histopathology by the use of autopsy sampling if post-mortem PSA data were informative. However, PSA forms and levels in autopsy sera have not been investigated., Materials and Methods: Paired ante- and post-mortem sera were collected for a series of cases. Total and free PSA levels in each were determined and compared. These PSA data were correlated with corresponding changes in serum electrolyte levels., Results: Total PSA levels were similar in ante- and post-mortem sera if autopsy blood was drawn by approximately 24 hours following the time of death. Free PSA levels, however, were increased approximately two-fold in most post-mortem sera analyzed. Increases in the serum electrolytes potassium, magnesium and phosphate correlated positively with increases in free PSA., Conclusion: Total PSA levels in ante- and post-mortem sera were comparable. Free PSA levels had approximately doubled by autopsy, but may be normalized in relation to increases in serum electrolyte levels. The use of autopsy prostates and PSA data would avoid diagnostic bias from use of clinical material and permit extensive analysis to be carried out, which is not normally feasible with live subjects.

Unlabelled: Abdominal aortic aneurysms have been treated by open operative repair for many years. A frequent rate of morbidity is associated with the natural history of abdominal aortic aneurysms in combination with open surgical repair. Recently a new technique that is less surgically invasive has been developed as an alternative to open repair. The present case report outlines a less invasive anesthetic technique for the morbidly obese patient., Implications: This case report discusses a minimally invasive anesthetic approach towards the morbidly obese patient undergoing endovascular abdominal aortic aneurysm repair. It demonstrates a safe and cost-effective means of managing a patient with numerous comorbidities. We also discuss an anesthetic/surgical approach on how to provide maximum analgesia with minimal anesthesia.

It is 6 years since specialist training in the UK was radically reformed. Is educational quality still improving or have early improvements slipped as the novelty has worn off? What further improvements are needed to ensure the production of specialists who are properly prepared to be the consultants of the future? The authors address these questions from the perspective of one postgraduate deanery.

In order to evaluate the chronic in vivo effects of excessive catecholamine levels, and the potential for spontaneous reversibility of these effects, we employed a chronic two-week infusion of epinephrine in rats. Epinephrine infusion resulted in myocyte hypertrophy, left ventricular fibrotic degenerative changes, diminished response to adrenergic stimuli, and enhanced left ventricular papillary contractile responses to calcium. Two weeks after cessation of the epinephrine infusion, left ventricular fibrotic degenerative changes were reduced, and responses to adrenergic stimuli were partially restored. However, myocyte hypertrophy and the enhanced responses to calcium persisted in these animals. This study indicates the potential for spontaneous reversal of some of epinephrine's toxic effects, and further implies that the loss in adrenergic sensitivity in epinephrine-treated animals may be a desensitization phenomenon, while the alterations in calcium response are less readily reversed.